myselfshy

Author Archive


Genital warts (or condylomata acuminata, venereal warts, anal warts and anogenital warts) are symptoms of a highly contagious sexually transmitted disease caused by some types of human papillomavirus (HPV). It is spread through direct skin-to-skin contact, usually during oral, genital, or anal sex with an infected partner. Warts are the most easily recognized symptom of genital HPV infection. Although some types of HPV are known to cause cervical cancer and anal cancers, these are not the same types of HPV that cause genital warts. Although 90% of those who contract HPV will not develop genital warts, those infected can still transmit the virus. Although estimates of incidence vary between studies, HPV is so common that nearly all sexually active people will get it at some point in their lives.
HPV types 6 and 11 are most frequently the cause of genital warts. The Gardasil vaccine includes coverage for these types. While types 6 and 11 are considered low risk for progression to cancers, it is also possible to be infected with different varieties of HPV, such as a low-risk HPV that causes warts and a high-risk HPV, either at the same or different times.
A condyloma acuminatum is a single genital wart, and condylomata acuminata are multiple genital warts. The word roots mean “pointed wart” (kondylos Greek κονδυλος, “knuckle” + -oma Greek ωμα, “disease” = kondyloma, “knuckle-like growth”; acuminatum Latin=”pointed”).
CAUSES
Transmission
HPV is most commonly transmitted through penetrative sex. While HPV can also be transmitted via non-penetrative sexual activity, it is less transmissible than via penetrative sex. There is conflicting evidence about the effect of condoms on transmission of low-risk HPV. Some studies have suggested that they are effective at reducing transmission. Other studies suggest that condoms are not effective at preventing transmission of the low-risk HPV variants that cause genital warts. The effect of condoms on HPV transmission may also be gender-dependent; there is some evidence that condoms are more effective at preventing infection of males than of females.
The types of HPV that cause warts are highly transmissible. Roughly three out of four unaffected partners of patients with warts develop them within eight months. Other studies of partner concordance suggest that the presence of visible warts may be an indicator of increased infectivity; HPV concordance rates are higher in couples where one partner has visible warts.
Latency and recurrence
Although 90% of HPV infections are cleared by the body within two years of infection, it is possible for infected cells to undergo a latency (quiet) period, with the first occurrence or a recurrence of symptoms happening months or years later. Latent HPV, even with no outward symptoms, is still transmissible to a sexual partner. If an individual has unprotected sex with an infected partner, there is a 70% chance that he or she will also become infected.
In individuals with a history of previous HPV infection, the appearance of new warts may be either from a new exposure to HPV, or from a recurrence of the previous infection. As many as one-third of people with warts will experience a recurrence.
In children
Anal or genital warts may be transmitted during birth. The presence of wart-like lesions on the genitals of young children has been suggested as an indicator of sexual abuse. However, genital warts can sometimes result from autoinoculated by warts elsewhere on the body, such as from the hands. It has also been reported from sharing of swimsuits, underwear, or bath towels, and from non-sexual touching during routine care such as diapering. Genital warts in children are less likely to be caused by HPV subtypes 6 and 11 than adults, and more likely to be caused by HPV types that cause warts elsewhere on the body (“cutaneous types”). Surveys of pediatricians who are child abuse specialists suggest that in children younger than 4 years old, there is no consensus on whether the appearance of new anal or genital warts, by itself, can be considered an indicator of sexual abuse.
DIAGNOSIS
The diagnosis of genital warts is most often made visually, but may require confirmation by biopsy in some cases. Smaller warts may occasionally be confused with molluscum contagiosum. Genital warts, histopathologically, characteristically rise above the skin surface due to enlargement of the dermal papillae, have parakeratosis and the characteristic nuclear changes typical of HPV infections (nuclear enlargement with perinuclear clearing). DNA tests are available for diagnosis of high-risk HPV infections. Because genital warts are caused by low-risk HPV types, DNA tests cannot be used for diagnosis of genital warts or other low-risk HPV infections.
Some practitioners use an acetic acid solution to identify smaller warts (“subclinical lesions”), but this practice is controversial. Because a diagnosis made with acetic acid will not meaningfully affect the course of the disease, and cannot be verified by a more specific test, a 2007 UK guideline advises against its use.
EPIDEMIOLOGY
Genital HPV infections have an estimated prevalence in the US of 10-20% and clinical manifestations in 1% of the sexually active adult population. US incidence of HPV infection has increased between 1975 and 2006. About 80% of those infected are between the ages of 17-33. Although treatments can remove the warts, they do not remove the HPV, so warts can recur after treatment (about 50-73% of the time). Warts can also spontaneously regress (with or without treatment).
Traditional theories postulated that the virus remained in the body for a lifetime. However, studies using sensitive DNA techniques have shown that through immunological response the virus can either be cleared or suppressed to levels below what polymerase chain reaction (PCR) tests can measure. One study testing genital skin for subclinical HPV using PCR found a prevalence of 10%.
SIGNS AND SYMPTOMS
Genital warts may occur singly but are more often found in clusters. They may be found anywhere in the anal or genital area, and are frequently found on external surfaces of the body, including the penile shaft, scrotum, labia majora of the vagina, or around the anus. They can also occur on internal surfaces like the opening to the urethra, inside the vagina, on the cervix, or in the anus. In males they are frequently found on or around the head of the penis.
They can be as small as 1-5mm in diameter, but can also grow or spread into large masses in the genital or anal area. In some cases they look like small stalks. They may be hard (“keratinized”) or soft. Their color can be variable, and sometimes they may bleed.
In most cases, there are no symptoms of HPV infection other than the warts themselves. Sometimes warts may cause itching, redness, or discomfort, especially when they occur around the anus. Although they are usually without other physical symptoms, an outbreak of genital warts may cause psychological distress, such as anxiety, in some people.
MANAGEMENT
There is no cure for HPV. Existing treatments are focused on the removal of visible warts, but these may also regress on their own without any therapy. There is no evidence to suggest that removing visible warts reduces transmission of the underlying HPV infection. As many as 80% of people with HPV will clear the infection within 18 months.
A healthcare practitioner may offer one of several ways to treat warts, depending on their number, sizes, locations, or other factors. All treatments can potentially cause depigmentation, itching, pain, or scarring.
Treatments can be classified as either physically ablative, or topical agents. Physically ablative therapies are considered more effective at initial wart removal, but like all therapies have significant recurrence rates.
Many therapies, including folk remedies, have been suggested for treating genital warts, some of which have little evidence to suggest they are effective or safe. Those listed here are ones mentioned in national or international practice guidelines as having some evidence basis for their use.
Physical ablation
Physically ablative methods are more likely to be effective on keratinized warts. They are also most appropriate for patients with fewer numbers of relatively smaller warts.
Simple excision, such as with scissors under local anesthesia, is highly effective.

Liquid nitrogen cryosurgery is usually performed in an office visit, at weekly intervals. It is effective, inexpensive, safe for pregnancy, and does not usually cause scarring.

Electrocauterization (sometimes called “loop electrical excision procedure” or LEEP) is procedure with a longer history of use, and is considered effective.

Laser ablation has less evidence to suggest its use. It may be less effective than other ablative methods. It is extremely expensive, and often used as a last resort.

Formal surgical procedures, performed by a specialist under general anesthesia, may be necessary for larger or more extensive warts, intra-anal warts, or warts in children. It carries a greater risk of scarring than other methods.

Topical agents
A 0.15-0.5% podophyllotoxin (also called podofilox) solution in a gel or cream. Marketed as Condylox (0.5%), Wartec (0.15%) and Warticon (0.15%), it can be applied by the patient to the affected area and is not washed off. It is the purified and standardized active ingredient of the podophyllin (see below). Podofilox is safer and more effective than podophyllin. Skin erosion and pain are more commonly reported than with imiquimod and sinecatechins. Its use is cycled (2 times per day for 3 days then 4-7 days off); one review states that it should only be used for four cycles.

Imiquimod (Aldara) is a topical immune response cream, applied to the affected area. It causes less local irritation than podofilox but may cause fungal infections (11% in package insert) and flu-like symptoms (less than 5% disclosed in package insert).

Sinecatechins (marketed as Veregen and Polyphenon E) is an ointment of catechins (55% epigallocatechin gallate) extracted from green tea and other components. Mode of action is undetermined. It appears to have higher clearance rates than podophyllotoxin and imiquimod and causes less local irritation, but clearance takes longer than with imiquimod.

Trichloroacetic acid (TCA) is less effective than cryosurgery, and is not recommended for use in the vagina, cervix, or urinary meatus.

Interferon can be used; it is effective, but it is also expensive and its effect is inconsistent.

Discontinued

:

A 5% 5-fluorouracil (5-FU) cream was used, but it is no longer considered an acceptable treatment due to the side-effects.

Podophyllin, podofilox and Isotretinoin should not be used during pregnancy, as they could cause birth defects in the fetus.
PREVENTION
Gardasil (sold by Merck & Co.) is a vaccine that protects against human papillomavirus types 16, 18, 6, and 11. Types 6 and 11 cause genital warts, while 16 and 18 cause cervical cancer. The vaccine is preventive, not therapeutic, and must be given before exposure to the virus type to be effective, ideally before the beginning of sexual activity. The vaccine is approved by the US Food and Drug Administration for use in both males and females as early as 9 years of age.
In the UK, Gardasil replaced Cervarix in September 2012 for reasons unrelated to safety. Cervarix had been used routinely in young females from its introduction in 2008, but was only effective against the high-risk HPV types 16 and 18, neither of which typically causes warts.

Advertisements

SUMMARY

Folliculitis (also known as hot tub rash) is the infection and inflammation of one or more hair follicles. The condition may occur anywhere on the skin with the exception of the palms of the hands and soles of the feet. They may appear as red dots that come to white tips on the chest, back, arms, legs, and head.
CAUSES
Most carbuncles, furuncles, and other cases of folliculitis develop from Staphylococcus aureus and Pseudomonas aeruginosa.
Folliculitis starts when hair follicles are damaged by friction from clothing, an insect bite, blockage of the follicle, shaving, or braids too tight and too close to the scalp. In most cases of folliculitis, the damaged follicles are then infected with the bacterium Staphylococcus. Folliculitis usually affects those in their early adult life, and may persist till their early 30s. Warmer weather may worsen the condition.
Iron deficiency anemia is sometimes associated with chronic cases.
Fungal
Tinea barbae is similar to barber’s itch, but the infection is caused by the fungus T. rubrum.

Malassezia folliculitis, formerly known as Pityrosporum folliculitis, is caused by yeasts (fungi) of the genus Malassezia.

Bacterial
Hot-tub folliculitis is caused by the bacterium Pseudomonas aeruginosa. The folliculitis usually occurs after sitting in a hot tub that was not properly cleaned before use. Symptoms are found around the body parts that sit in the hot tub-typically the legs, hips, buttocks, and surrounding areas. Symptoms are typically amplified around regions that were covered by wet clothing, such as bathing suits.

Sycosis vulgaris, Sycosis barbae or Barber’s itch is a staphylococcus infection of the hair follicles in the bearded area of the face, usually the upper lip. Shaving aggravates the condition.

Gram-negative folliculitis may appear after prolonged acne treatment with antibiotics.

Viral
Herpetic folliculitis may occur when Herpes Simplex Virus infection spreads to nearby hair follicles – mostly around the mouth.

Non-infectious
Pseudofolliculitis barbae is a disorder occurring when hair curves back into the skin and causes inflammation.

Eosinophilic folliculitis may appear in persons with impaired immune systems.

Folliculitis decalvans or tufted folliculitis usually affects scalp. Several hairs arise from the same hair follicle. Scarring and permanent hair loss may follow. The cause is unknown.

Folliculitis keloidalis scarring on the nape of the neck, most common among males of curly hair.

Oil folliculitis is inflammation of hair follicles due to exposure to various oils and typically occurs on forearms or thighs. It is common in refinery workers, road workers, mechanics, and sheep shearers. Even makeup may cause it.

Malignancy may also be represented by recalcitrant cases.

TREATMENT
Topical antiseptic treatment is adequate for most cases

Topical antibiotics such as mupirocin or neomycin containing ointment

Some patients may benefit from systemic narrow-spectrum penicillinase-resistant penicillins (such as dicloxacillin in US, or flucloxacillin in UK)

Fungal folliculitis can worsen with antibiotics and may require an oral antifungal such as Fluconazole. Topical antifungals such as Econazole Nitrate may also be effective.

Folliculitis may reoccur even after symptoms have gone away.
SYMPTOMS
rash (reddened skin area)

itching skin

pimples or pustules located around a hair follicle

may crust over

typically occur on neck, armpit, or groin area

may present as genital lesions

spreading from leg to arm to body through improper treatment of antibiotics.


Kyphosis (from Greek κυφός kyphos, a hump), refers to the normal convex curvature of the spine as it occurs in the thoracic and sacral regions. Inward concave curving of the cervical and lumbar regions of the spine is called lordosis. The term kyphosis can also be used to describe excessive kyphosis or overcurvature when it is also known as hyperkyphosis. Kyphosis can be called roundback or Kelso’s hunchback. It can result from degenerative diseases such as arthritis; developmental problems, most commonly Scheuermann’s disease; osteoporosis with compression fractures of the vertebrae, or trauma. A normal thoracic spine extends from the 1st to the 12th vertebra and should have a slight kyphosis ranging from 20° to 45°. When the “roundness” of the upper spine increases past 45° it is called “hyperkyphosis”. Scheuermann’s kyphosis is the most classic form of hyperkyphosis and is the result of wedged vertebrae that develop during adolescence. The cause is not currently known and the condition appears to be multifactorial and is seen more frequently in males than females.>

In the sense of a deformity, it is the pathological curving of the spine, where parts of the spinal column lose some or all of their lordotic profile. This causes a bowing of the back, seen as a slouching posture.

While most cases of kyphosis are mild and only require routine monitoring, serious cases can be debilitating. High degrees of kyphosis can cause severe pain and discomfort, breathing and digestion difficulties, cardiovascular irregularities, neurological compromise and, in the more severe cases, significantly shortened life spans. These types of high-end curves typically do not respond well to conservative treatment and almost always warrant spinal fusion surgery, which can successfully restore the body’s natural degree of curvature. The Cobb angle is the preferred method of measuring kyphosis.

CLASSIFICATION

There are several kinds of kyphosis (ICD-10 codes are provided):

  • Postural kyphosis (M40.0), the most common type, normally attributed to slouching, can occur in both the old and the young. In the young, it can be called ‘slouching’ and is reversible by correcting muscular imbalances. In the old, it may be a case of hyperkyphosis and called ‘dowager’s hump’. About one third of the most severe hyperkyphosis cases in older people have vertebral fractures. Otherwise, the aging body does tend towards a loss of musculoskeletal integrity, and hyperkyphosis can develop due to aging alone.
  • Scheuermann’s kyphosis (M42.0) is significantly worse cosmetically and can cause varying degrees of pain, and can also affect different areas of the spine (the most common being the midthoracic area). Scheuermann’s kyphosis is considered a form of juvenile osteochondrosis of the spine, and is more commonly called Scheuermann’s disease. It is found mostly in teenagers and presents a significantly worse deformity than postural kyphosis. A patient suffering from Scheuermann’s kyphosis cannot consciously correct posture. The apex of the curve, located in the thoracic vertebrae, is quite rigid. The patient may feel pain at this apex, which can be aggravated by physical activity and by long periods of standing or sitting. This can have a significantly detrimental effect on their lives, as their level of activity is curbed by their condition; they may feel isolated or uneasy amongst peers if they are children, depending on the level of deformity. Whereas in postural kyphosis, the vertebrae and disks appear normal, in Scheuermann’s kyphosis, they are irregular, often herniated, and wedge-shaped over at least three adjacent levels. Fatigue is a very common symptom, most likely because of the intense muscle work that has to be put into standing and/or sitting properly. The condition appears to run in families. Most patients who undergo surgery to correct their kyphosis have Scheuermann’s disease.
  • Congenital kyphosis (Q76.4) can result in infants whose spinal column has not developed correctly in the womb. Vertebrae may be malformed or fused together and can cause further progressive kyphosis as the child develops. Surgical treatment may be necessary at a very early stage and can help maintain a normal curve in coordination with consistent follow-ups to monitor changes. However, the decision to carry out the procedure can be very difficult due to the potential risks to the child. A congenital kyphosis can also suddenly appear in teenage years, more commonly in children with cerebral palsy and other neurological disorders.
  • Nutritional kyphosis can result from nutritional deficiencies, especially during childhood, such as vitamin D deficiency (producing rickets), which softens bones and results in curving of the spine and limbs under the child’s body weight.
  • Gibbus deformity is a form of structural kyphosis, often a sequelato tuberculosis.
  • Post-traumatic kyphosis (M84.0) can arise from untreated or ineffectively treated vertebral fractures.

TREATMENTS

A diagnosis of kyphosis is generally made through observation and measurement. Idiopathic causes, such as vertebral wedging or other abnormalities, can be confirmed through X-ray. Osteoporosis, a potential cause of kyphosis, can be confirmed with a bone density scan. Postural thoracic kyphosis can often be treated with posture reeducation and focused strengthening exercises.Idiopathic thoracic kyphosis due to vertebral wedging,fractures, or vertebral abnormalities is more difficult to manage, since assuming a correct posture may not be possible with structural changes in the vertebrae.Children who have not completed their growth may show long-lasting improvements with bracing. Exercises may be prescribed to alleviate discomfort associated with overstretched back muscles. A variety of gravity-assisted positions or gentle traction can minimize pain associated with nerve root impingement. Surgery may be recommended for severe idiopathic kyphosis.

Orthosis (brace)

Body braces showed benefit in a randomised controlled trial.

The Milwaukee brace is one particular body brace that is often used to treat kyphosis in the US. Modern CAD/CAM braces are used in Europe to treat different types of kyphosis. These are much easier to wear and have better in-brace corrections than reported for the Milwaukee brace. Since there are different curve patterns (thoracic, thoracolumbar and lumbar), different types of brace are in use, with different advantages and disadvantages.

Specialised physical therapy

In Germany, a standard treatment for both Scheuermann’s disease and lumbar kyphosis is the Schroth method, a system of physical therapy for scoliosis and related spinal deformities. It involves lying supine, placing a pillow under the scapular region and posteriorly stretching the cervical spine.

Surgery

Surgical treatment can be used in severe cases. In patients with progressive kyphotic deformity due to vertebral collapse, a procedure called a kyphoplasty may arrest the deformity and relieve the pain. Kyphoplasty is a minimally invasive procedure, requiring only a small opening in the skin. The main goal is to return the damaged vertebra as close as possible to its original height. Taking into account that signs and symptoms of spinal deformity cannot be changed by surgical intervention, surgery remains to be a cosmetic indication. Unfortunately, the cosmetic effects of surgery are not necessarily stable.


cramp is a sudden, severe, and involuntary muscle contraction or over-shortening; while generally temporary and non-damaging, they can cause mild-to-excruciating pain, and a paralysis-like immobility of the affected muscle(s). Onset is usually sudden, and it resolves on its own over a period of several seconds, minutes, or hours. There are two major categories of cramps: causes of skeletal muscle cramps include muscle fatigue, and/or a lack of electrolytes (e.g., low sodium, low potassium, and/or low magnesium); cramps of smooth muscle tissue may be due to menstruation or gastroenteritis.

TREATMENT

Stretching, massage and drinking plenty of fluid, such as water, may be helpful in treating simple muscle cramps. With exertional heat cramps due to electrolyte abnormalities (primarily sodium loss and not calcium, magnesium, and potassium) appropriate fluids and sufficient salt improves symptoms.

Medication

Quinine is likely to be effective. However, due to side effects its use should only be considered if other treatments have failed and in light of these concerns. Vitamin B complex, naftidrofuryl, lidocaine, and calcium channel blockers may be effective for muscle cramps. Research has also shown that pickle juice can be an effective remedy based on its high sodium and electrolyte content.

PATHOPHYSIOLOGY

Skeletal muscles work as antagonistic pairs. Contracting one skeletal muscle requires the relaxation of the opposing muscle in the pair. Cramps can occur when muscles are unable to relax properly due to myosin fibers not fully detaching from actin filaments. In skeletal muscle, ATP must attach to the myosin heads for them to disassociate from the actin and allow relaxation – the absence of ATP in sufficient quantities means that the myosin heads remains attached to actin. An attempt to force a muscle cramped in this way to extend (by contracting the opposing muscle) can tear muscle tissue and worsen the pain. The muscle must be allowed to recover (resynthesize ATP), before the myosin fibres can detach and allow the muscle to relax.

PREVENTION

Adequate conditioning, stretching, mental preparation, and adequate fluid/electrolyte balance are likely helpful in preventing muscle cramps.

DIFFERENTIAL DIAGNOSIS

Causes of cramping include hyperflexion, hypoxia, exposure to large changes in temperature, dehydration, or low blood salt. Muscle cramps may also be a symptom or complication of pregnancy, kidney disease, thyroid disease, hypokalemia, hypomagnesemia or hypocalcemia (as conditions), restless-leg syndrome, varicose veins, and multiple sclerosis.

Electrolyte disturbance may cause cramping and muscle tetany, particularly hypokalaemia and hypocalcaemia. This disturbance arises as the body loses large amounts of interstitial fluid through sweat. This interstitial fluid comprises mostly water and salt (sodium chloride). The loss of osmotically active particles outside of muscle cells leads to a disturbance of the osmotic balance and therefore shrinking of muscle cells, as these contain more osmotically active particles. This causes the calcium pump between the muscle sarcoplasm and sarcoplasmic reticulum to short circuit; the calcium ions remain bound to the troponin, continuing muscle contraction.

As early as 1965, researchers observed that leg cramps and restless-leg syndrome result from excess insulin, sometimes called hyperinsulinemia. Hypoglycemia and reactive hypoglycemia are associated with excess insulin (or insufficient glucagon), and avoidance of low blood glucose concentration may help to avoid cramps.

Smooth muscle cramps

Smooth muscle contractions may be symptomatic of endometriosis or other health problems. Menstrual cramps may also occur both before and during a menstrual cycle.

Skeletal muscle cramps

Skeletal muscles can be voluntarily controlled, under normal circumstances. Skeletal muscles that cramp the most often are the calves, thighs, and arches of the foot, and are sometimes called a “Charley horse” or a “corkie”. Such cramping is associated with strenuous physical activity and can be intensely painful; however, they can even occur while inactive/relaxed. Around 40% of people who experience skeletal cramps are likely to endure extreme muscle pain, and may be unable to use the entire limb that contains the “locked-up” muscle group. It may take up to seven days for the muscle to return to a pain-free state.

Nocturnal leg cramps

Nocturnal leg cramps are involuntary muscle contractions that occur in the calves, soles of the feet, or other muscles in the body during the night or (less commonly) while resting.

The duration of nocturnal leg cramps is variable with cramps lasting anywhere from a few seconds to several minutes. Muscle soreness may remain after the cramp itself ends. These cramps are more common in older people. They happen quite frequently in teenagers and in some people while exercising at night. The precise cause of these cramps is unclear. Potential contributing factors include dehydration, low levels of certain minerals (magnesium, potassium, calcium, and sodium), and reduced blood flow through muscles attendant in prolonged sitting or lying down. Nocturnal leg cramps (almost exclusively calf cramps) are considered ‘normal’ during the late stages of pregnancy. They can, however, vary in intensity from mild to extremely painful.

Lactic acid can build up around the muscles which can trigger cramps; however, these happen during anaerobic respiration which happens when a person is exercising or engaging in an activity where the heart beat speeds up. Medical conditions associated with leg cramps are cardiovascular disease, cirrhosis, pregnancy, and lumbar canal stenosis.

Various medications may cause nocturnal leg cramps:

  • Diuretics, especially potassium sparing
  • Long acting adrenergic beta-agonists (LABAs)
  • Hydroxymethylglutaryl-coenzyme A reductase inhibitors (HMG-CoA inhibitors or statins)

Besides being painful, a nocturnal leg cramp can cause much distress and anxiety.

Gentle stretching and massage, putting some pressure on the affected leg by walking or standing, or taking a warm bath or shower may help to end the cramp. If the cramp is in the calf muscle, pulling the big toe gently backwards will stretch the muscle and, in some cases, cause almost immediate relief.

Iatrogenic causes

Statins may sometimes cause myalgia and cramps among other possible side effects. Raloxifene (Evista) is a medication associated with a high incidence of leg cramps. Additional factors, which increase the probability for these side effects, are physical exercise, age, female gender, history of cramps, and hypothyroidism. Up to 80% of athletes using statins suffer significant adverse muscular effects, including cramps; the rate appears to be approximately 10-25% in a typical statin-using population. In some cases, adverse effects disappear after switching to a different statin; however, they should not be ignored if they persist, as they can, in rare cases, develop into more serious problems. Coenzyme Q10 supplementation can be helpful to avoid some statin-related adverse effects, but currently there is not enough evidence to prove the effectiveness in avoiding myopathy or myalgia.


miscarriage is the natural death of an embryo or fetus in the womb. It takes place in the early stages of prenatal development prior to fetal viability (the stage of potential independent survival). Among women who know they are pregnant, the miscarriage rate is roughly 15-20% and it is the most common complication of early pregnancy in humans.

CAUSES

Among women who know they are pregnant, the miscarriage rate is roughly 15-20%. Miscarriage may occur for many reasons, not all of which can be identified. Some of these causes include genetic, uterine, or hormonal abnormalities, reproductive tract infections, and tissue rejection. Miscarriage caused by invasive prenatal diagnosis (chorionic villus sampling (CVS) and amniocentesis) is rare (about 1%).

First trimester

Most clinically apparent miscarriages (two-thirds to three-quarters in various studies) occur during the first trimester. The National Institutes of Health report that “around half of all fertilized eggs die and are lost (aborted) spontaneously, usually before the woman knows she is pregnant.”

Chromosomal abnormalities are found in more than half of embryos miscarried in the first 13 weeks. Chromosomal problems due to a parent’s genes are, however, a possibility. This is more likely to have been the cause in the case of a woman suffering repeated miscarriages, or if one of the parents has a child or other relatives with birth defects. Genetic problems are more likely to occur with older parents; this may account for the higher rates observed in older women.

Progesterone deficiency may be another cause. Women diagnosed with low progesterone levels in the second half of their menstrual cycle (luteal phase) may be prescribed progesterone supplements, to be taken for the first trimester of pregnancy. No study has shown that general first-trimester progesterone supplements reduce the risk however, (when a mother might already be losing her baby), and even the identification of problems with the luteal phase as a contributing factor has been questioned.

Second trimester

Second trimester losses may be due to uterine malformation, growths in the uterus (fibroids), or cervical problems. These conditions also may contribute to premature birth.

One study found that 19% of second trimester losses were caused by problems with the umbilical cord. Problems with the placenta also may account for a significant number of later-term miscarriages.

Risk factors

Multiple pregnancy

Pregnancies of more than one fetus, i.e. twins, triplets, etc., are considered at increased risk. The more fetuses in the womb, the higher the risk

Intercurrent diseases

Several intercurrent diseases in pregnancy can potentially increase the risk of miscarriage, including:

  • Diabetes mellitus; The risk of miscarriage is increased in women with poorly controlled insulin-dependent diabetes mellitus. This 1998 prospective study found that the risk increased by 3.1% (over the background risk of about 16%) for each standard deviation in glycosylated haemoglobin above the normal range. The risk was not found to be significantly increased in women with good glycaemic control in early pregnancy.
  • Polycystic ovary syndrome, which may increase the risk of miscarriage, but this is disputed. Two studies suggested treatment with the drug metformin significantly lowers the rate of miscarriage in women with PCOS, but the quality of these studies has been questioned. A 2006 review of metformin treatment in pregnancy found insufficient evidence of safety, and did not recommend routine treatment with the drug. In 2007 the Royal College of Obstetricians and Gynaecologists also recommended against use of the drug to prevent miscarriage.
  • Hypothyroidism; Severe cases of hypothyroidism increase the risk of miscarriage. The effect of milder cases of hypothyroidism on miscarriage rates has not been established. The presence of certain immune conditions such as autoimmune diseases is associated with a greatly increased risk. The presence of anti-thyroid autoantibodies is associated with an increased risk with an odds ratio of 3.73 and 95% confidence interval 1.8-7.6.
  • Vertically transmitted infections; Certain vertically transmitted infections (such as rubella and chlamydia) increase the risk.
  • Autoimmune disease; Some research suggests autoimmunity as a possible cause of recurrent or late-term miscarriages. Autoimmune disease occurs when the body’s own immune system acts against itself. Therefore, in the case of an autoimmune-induced miscarriages the woman’s body attacks the growing fetus or prevents normal pregnancy progression. Further research also has suggested that autoimmune disease may cause genetic abnormalities in embryos which in turn may lead to miscarriage. As an example, Celiac disease increases the risk of miscarriage by an odds ratio of approximately 1.4.

Smoking

Tobacco (cigarette) smokers have an increased risk of miscarriage. An increase in the rates also is associated with the father being a cigarette smoker. The husband study observed a 4% increased risk for husbands who smoke fewer than 20 cigarettes/day, and an 81% increased risk for husbands who smoke 20 or more cigarettes/day.

Age

The age of the mother is a significant risk factor. Miscarriage rates increase steadily with age, with more substantial increases after age 35.

Several other factors have been correlated with higher rates in some research, but whether they cause the miscarriages is debated. No causal mechanism may be known, the studies showing a correlation may have been retrospective (beginning the study after the miscarriages occurred, which may introduce bias) rather than prospective (beginning the study before the women became pregnant), or both. A greater correlation has been shown in the following categories, however.

Morning sickness

Nausea and vomiting of pregnancy (NVP, or morning sickness) are associated with a decreased risk. Several proximate causes have been proposed for this relationship, but none are widely agreed upon. NVP is generally interpreted as a defense mechanism which discourages the mother’s ingestion of foods that are harmful to the fetus; according to this model, a lower frequency of miscarriage would be an expected consequence of the different food choices made by a women experiencing NVP.

Exercise

A study of more than 92,000 pregnant women found that most types of exercise (with the exception of swimming) correlated with a higher risk of miscarrying prior to 18 weeks. Increasing time spent on exercise was associated with a greater risk: an approximately 10% increased risk was seen with up to 1.5 hours per week of exercise, and a 200% increased risk was seen with more than 7 hours per week of exercise. However, the study found none of these risks to be statistically significant. High-impact exercise was especially associated with the increased risk. No relationship was found between exercise rates after the 18th week of pregnancy. The majority of miscarriages had already occurred at the time women were recruited for the study, and no information on nausea during pregnancy or exercise habits prior to pregnancy was collected.

Caffeine

Caffeine consumption also has been correlated to miscarriage rates, at least at higher levels of intake. However, such higher rates have been found to be statistically significant only in certain circumstances. A 2007 study of more than 1,000 pregnant women found that those who reported consuming 200& mg or more of caffeine per day experienced a 25% rate, compared to 13% among women who reported no caffeine consumption. 200& mg of caffeine is present in 10& oz (300& mL) of coffee or 25& oz (740& mL) of tea. This study controlled for pregnancy-associated nausea and vomiting (NVP or morning sickness): the increased rate for heavy caffeine users was seen regardless of how NVP affected the women. About half of the miscarriages had already occurred at the time women were recruited for the study. A second 2007 study of approximately 2,400 pregnant women found that caffeine intake up to 200& mg per day was not associated with increased rates (the study did not include women who drank more than 200& mg per day past early pregnancy). A prospective cohort study in 2009 found that light or moderate caffeine consumption (up to 300& mg per day) had no effect on pregnancy or miscarriage rates.

Other

Sexual intercourse during the first trimester has often been said or assumed by doctors to be a cause of miscarriage. However the association has never been proved or disproved. Physical trauma, exposure to environmental toxins, and use of an IUD during the time of conception have also been linked to increased risk.

Loop electrosurgical excision procedure (LEEP) is one of the most commonly used approaches to treat high grade cervical dysplasia. A cohort study came to the result that women with a time interval from LEEP to pregnancy of less than 12 months compared with 12 months or more were at significantly increased risk for spontaneous abortion, with risk of spontaneous abortion of 18% compared with 4.6%, respectively. On the other hand, no increased risk was identified for preterm birth after LEEP.

Antidepressants, especially paroxetine and venlafaxine, can lead to a miscarriage.

DIAGNOSIS

A miscarriage may be confirmed via obstetric ultrasound and by the examination of the passed tissue. When looking for microscopic pathologic symptoms, one looks for the products of conception. Microscopically, these include villi, trophoblast, fetal parts, and background gestational changes in the endometrium. As many as half the embryos miscarried have a chromosomal abnormality. When chromosomal abnormalities are found in more than one miscarriage, genetic testing of both parents may be done.

Ultrasound criteria

A review article in The New England Journal of Medicine based on a consensus meeting of the Society of Radiologists in Ultrasound in America (SRU) has suggested that miscarriage should be diagnosed only if any of the following criteria are met upon ultrasonography visualization:

  • Crown-rump length of at least 7& mm and no heartbeat.
  • Mean gestational sac diameter of at least 25& mm and no embryo.
  • Absence of embryo with heartbeat at least 2 weeks after an ultrasound scan that showed a gestational sac without a yolk sac.
  • Absence of embryo with heartbeat at least 11 days after an ultrasound scan that showed a gestational sac with a yolk sac.

In addition, signs upon ultrasonography that are suggested to be suspicious for miscarriage, but not diagnostic of it, include:

  • Crown-rump length of less than 7& mm and no heartbeat.
  • Mean gestational sac diameter of 16-24& mm and no embryo.
  • Absence of embryo with heartbeat 7-13 days after an ultrasound scan that showed a gestational sac without a yolk sac.
  • Absence of embryo with heartbeat 7-10 days after a scan that showed a gestational sac with a yolk sac.
  • Absence of embryo at least 6 weeks after last menstrual period.
  • Amniotic sac seen adjacent to yolk sac, and with no visible embryo.
  • Yolk sac of more than 7& mm.
  • Small gestational sac compared to embryo size (less than 5& mm difference between mean sac diameter and crown-rump length).

Classification

The clinical presentation of a threatened miscarriage describes any bleeding seen during pregnancy prior to viability, that has yet to be assessed further. At investigation it may be found that the fetus remains viable and the pregnancy continues without further problems.

Alternatively the following terms are used to describe pregnancies that do not continue:

  • An empty sac is a condition where the gestational sac develops normally, while the embryonic part of the pregnancy is either absent or stops growing very early. Other terms for this condition are blighted ovum and anembryonic pregnancy.
  • An inevitable miscarriage describes a condition in which the cervix has already dilated open, but the fetus has yet to be expelled. This usually will progress to a complete miscarriage. The fetal heart beat may have been shown to have stopped, but this is not part of the criteria.
  • complete miscarriage is when all products of conception have been expelled. Products of conceptionmay include the trophoblast, chorionic villi, gestational sac, yolk sac, and fetal pole (embryo); or later in pregnancy the fetus, umbilical cord, placenta, amniotic fluid, and amniotic membrane. The presence of a pregnancy test that is still positive as well as an empty uterus upon transvaginal ultrasonography does, however, fulfill the definition of pregnancy of unknown location. Therefore, there may be a need for e.g. follow-up pregnancy tests to ensure that there is no remaining pregnancy, including any ectopic one.
  • An incomplete miscarriage occurs when some products of conception have been passed, but some remainsin utero. However, an increased distance between the uterine walls on transvaginal ultrasonography may also simply be an increased endometrial thickness and/or a polyp. The use of power Doppler may be better in confirming the presence of significant retained products of conception in the uterine cavity. In cases of uncertainty, there is a need to exclude an ectopic pregnancy, such as by serial beta-hCG measurements.

    • missed miscarriage is when the embryo or fetus has died, but a miscarriage has not yet occurred. It is also referred to as delayed miscarriage orsilent miscarriage.

    The following two terms consider wider complications or implications of a miscarriage:

    • septic miscarriage occurs when the tissue from a missed or incomplete miscarriage becomes infected. The infection of the uterus carries risk of spreading infection (septicaemia) and is a grave risk to the life of the woman.
    • Recurrent pregnancy loss(RPL) or recurrent miscarriage is the occurrence of three consecutive miscarriages. If the proportion of pregnancies ending in miscarriage is 15% and assuming that miscarriages are independent events, then the probability of two consecutive miscarriages is 2.25% and the probability of three consecutive miscarriages is 0.34%. The occurrence of recurrent pregnancy loss is 1%. A large majority (85%) of women who have had two miscarriages will conceive and carry normally afterward.

      The physical symptoms of a miscarriage vary according to the length of pregnancy:

      • At up to six weeks only small blood clots may be present, possibly accompanied by mild cramping or period pain.
      • At 6 to 13 weeks a clot will form around the embryo or fetus, and the placenta, with many clots up to 5& cm in size being expelled prior to completion of the process. The process may take a few hours or be on and off for a few days. Symptoms vary widely and may include vomiting and loose bowels, possibly due to physical discomfort.
      • At more than 13 weeks the fetus may be passed easily from the uterus, however the placenta is more likely to be fully or partially retained in the uterus, resulting in an incomplete miscarriage. The physical signs of bleeding, cramping, and pain may be similar to an early stage abortion, but sometimes more severe and labor-like.

      ICD10 codes

      • Habitual abortion
      • Incomplete abortion
      • Missed abortion
      • Threatened abortion
      N96<br> O03.0-O06.4<br> O02.1<br> O20.0

EPIDEMIOLOGY

Determining the precise prevalence of miscarriage is not possible, because a large number of miscarriages occur before pregnancies become established and before women are aware they are pregnant. In addition, women with bleeding in early pregnancy may attend for medical care more often than women not experiencing bleeding. Some studies have attempted to account for this by recruiting women who are planning pregnancies and testing for very early pregnancy, although these would also not be representative of the wider population. A systematic review found that the cumulative risk of miscarriage between 5 and 20 weeks of gestation varied from 11% to 22% in studies assessing miscarriage rates. Up to the 13th week of pregnancy, the risk of miscarriage each week was around 2%, dropping to 1% in week 14 and reducing slowly between 14 and 20 weeks.

The prevalence of miscarriage increases with the age of the mother and the father. In a Danish register-based study where the prevalence of miscarriage was 11%, the prevalence rose from 9% in women at 22 years of age to 84% by 48 years of age.

SIGNS AND SYMPTOMS

The most common symptom of a miscarriage is vaginal bleeding. This can vary from light spotting or brownish discharge to heavy bleeding and bright red blood. The bleeding may come and go over several days. However, light vaginal bleeding is relatively common during the first trimester of pregnancy (the first 12 weeks) and does not necessarily indicate a miscarriage.

Bleeding during pregnancy may be referred to as a threatened miscarriage. Of women who seek clinical treatment for bleeding during pregnancy, about half will miscarry. Symptoms other than bleeding are not statistically related.

Miscarriage may be detected during an ultrasound exam, or through serial human chorionic gonadotropin (HCG) testing. Women pregnant from assisted reproductive technology methods, and women with a history of aborting, may be monitored closely and so detection is sooner than women without such monitoring.

It is estimated about half of early miscarriages will be fully expelled naturally. Several medical options exist for managing documented nonviable pregnancies that have not been expelled naturally, such as medicinal treatment or a dilation and curettage (D&C) procedure. An ERPC, or evacuation of retained products of conception, may be performed to remove the remains of a pregnancy and the placental tissue from the uterus.>

MANAGEMENT

Bleeding during early pregnancy is the most common symptom of both impending miscarriage and of ectopic pregnancy. Pain does not strongly correlate with the former, but is a common symptom of ectopic pregnancy. Typically, in the case of blood loss, pain, or both, transvaginal ultrasound is performed. If a viable intrauterine pregnancy is not found with ultrasound, serial βHCG tests should be performed to rule out ectopic pregnancy, which is a life-threatening situation.

If the bleeding is light, making an appointment to see one’s doctor is recommended. If bleeding is heavy, there is considerable pain, or there is a fever, then seeking emergency medical attention is recommended.

Whilst bed rest has been advocated in the past to help ensure that a threatened pregnancy might continue, and in one study possibly helped when small subchorionic hematoma had been found on ultrasound scans, the prevailing opinion is that this is of no proven benefit.

Methods

No treatment is necessary for a diagnosis of complete miscarriage (so long as ectopic pregnancy is ruled out). In cases of an incomplete miscarriage, empty sac, or missed abortion there are three treatment options:

  • With no treatment (watchful waiting), most of these cases (65-80%) will pass naturally within two to six weeks. This path avoids the side effects and complications possible from medications and surgery, but increases the risk of mild bleeding, need for unplanned surgical treatment, and incomplete miscarriage.
    • Medical management usually consists of using misoprostol (a prostaglandin, brand name Cytotec) to encourage completion of the natural process. About 95% of cases treated with misoprostol will complete within a few days.
    • Surgical treatment is the fastest way to complete the process. It also shortens the duration and heaviness of bleeding, and avoids the physical pain associated with the miscarriage. In cases of repeated spontaneous abortions, D&C is also the most convenient way to obtain tissue samples for karyotype analysis (cytogenetic or molecular), although it is also possible to do with expectant and medical management, including the following techniques:
    • Vacuum aspiration, sometimes referred to as dilation and evacuation (D&E), uses aspiration to remove uterine contents through the cervix.
    • Dilation and curettage (D&C), which involves dilation (widening/opening) of the cervix and surgical removal of part of the lining of the uterus and/or contents of the uterus by scraping and scooping (curettage). D&C has a higher risk of complications compared to non-surgical treatment, including risk of injury to the cervix (e.g. cervical incompetence) and uterus, perforation of the uterus, and potential scarring of the intrauterine lining (Asherman’s syndrome). This is an important consideration for women who would like to have children in the future and want to preserve their fertility and reduce the chance of future pregnancy complications.

Aphthous stomatitis (also termedrecurrent aphthous stomatitisrecurring oral aphthae or recurrent aphthous ulceration) is a common condition characterized by the repeated formation of benign and non-contagious mouth ulcers (aphthae), in otherwise healthy individuals. The informal term canker sores is also used, mainly in North America.

The cause is not completely understood, but involves a T cell-mediated immune response triggered by a variety of factors. Individuals vary in their observed triggers, which may include nutritional deficiencies, local trauma, stress, hormonal influences, allergies, genetic predisposition and other factors.

These ulcers occur periodically and heal completely between attacks. In the majority of cases, the individual ulcers last about 7-10 days, and ulceration episodes occur 3-6 times per year. Most appear on the non-keratinizing epithelial surfaces in the mouth (i.e. anywhere except the attached gingiva, the hard palate and the dorsum of the tongue), although the more severe forms, which are less common, may also involve keratinizing epithelial surfaces. Symptoms range from a minor nuisance to interfering with eating and drinking. The severe forms may be debilitating, even causing weight loss due to malnutrition.

The condition is very common, affecting about 20% of the general population to some degree. The onset is often during childhood or adolescence, and the condition usually lasts for several years before gradually disappearing. There is no cure, and treatments aim to manage pain, promote healing and reduce the frequency of episodes of ulceration.

CAUSES

The cause is not entirely clear, but is thought to be multifactorial. It has even been suggested that aphthous stomatitis is not a single entity but rather a group of conditions with different causes. Multiple research studies have attempted to identify a causative organism, but aphthous stomatitis appears to be non-contagious, non-infectious and not sexually transmissible. The mucosal destruction is thought to be the result of a T cell (T lymphocyte) mediated immune response which involves the generation of interleukins and tumor necrosis factor alpha (TNF-α). Mast cells and macrophages are also involved, secreting TNF-α along with the T cells. When early aphthous ulcers are biopsied, the histologic appearance shows a dense inflammatory infiltrate, 80% of which is made up of T cells. Persons with aphthous stomatitis have circulating lymphocytes which react with peptides 91-105 of heat shock protein 65-60. Furthermore, the ratio of CD4+ T cells to CD8+ T cells in the peripheral blood of individuals with aphthous stomatitis is decreased.

Despite this preferred theory of immuno-dysregulation held by most researchers, aphthous stomatitis behaves dis-similarly to autoimmune diseases in many regards. There is no association between aphthous stomatitis and other autoimmune diseases, which often accompany each other; common autoantibodies are not detected, the condition tends to resolve spontaneously with advancing age rather than worsen, and usually serum immunoglobulins are at normal levels.

Evidence for the T cell-mediated mechanism of mucosal destruction is strong, but the exact triggers for this process are unknown and are thought to be multiple and varied from one person to the next. This suggests that there are a number of possible triggers, each of which is capable of producing the disease in different subgroups. In other words, different subgroups of individuals with aphthous stomatitis appear to have different causes for the condition. These sub-groups have been considered to be in three general groups, namely primary immuno-dysregulation, decrease of the mucosal barrier and states of heightened antigenic sensitivity. Etiologic factors in aphthous stomatitis are also sometimes considered in 2 categories, host-related or environmental.

Immunity

At least 40% of people with aphthous stomatitis have a positive family history, suggesting that some people are genetically predisposed to suffering with oral ulceration. HLA-B12, HLA-B51, HLA-Cw7, HLA-A2, HLA-A11, and HLA-DR2 are examples of human leukocyte antigen types associated with aphthous stomatitis. However, these HLA types are inconsistently associated with the condition, and also vary according to ethnicity. People who have a positive family history of aphthous stomatitis tend to develop a more severe form of the condition, and at an earlier age than is typical.

Stress has effects on the immune system, which may explain why some cases directly correlate with stress. It is often stated that ulceration is exacerbated during examination periods and lessened during periods of vacation. Alternatively, it has been suggested that oral parafunctional activities such as lip or cheek chewing become more pronounced during periods of stress, and hence the mucosa is subjected to more minor trauma.

Aphthous-like ulceration also occurs in conditions involving systemic immuno-dysregulation, e.g. cyclic neutropenia and human immunodeficiency virus infection. In cyclic neutropenia, more severe oral ulceration occurs during periods of severe immuno-dysregulation, and resolution of the underlying neutropenia prevents the cycle of ulceration. The relative increase in percentage of CD8+ T cells, caused by a reduction in numbers of CD4+ T cells may be implicated in RAS-type ulceration in HIV infection.

Mucosal barrier

The thickness of the mucosa may be an important factor in aphthous stomatitis. Usually, ulcers form on non keratinizing mucosal surfaces in the mouth. Factors which decrease the thickness of mucosa increase the frequency of occurrence, and factors which increase the thickness of the mucosa correlate with decreased ulceration.

The nutritional deficiencies associated with aphthous stomatitis (B12, folate, and iron) can all cause a decrease in the thickness of the oral mucosa (atrophy).

Local trauma is also associated with aphthous stomatitis, and it is known that trauma can decrease the mucosal barrier. Trauma could occur during injections of local anesthetic in the mouth, or otherwise during dental treatments, frictional trauma from a sharp surface in the mouth such as broken tooth, or from tooth brushing.

Hormonal factors are capable of altering the mucosal barrier. In one study, a small group of females with apthous stomatitis had fewer occurrences of aphthous ulcers during the luteal phase of the menstrual cycle or with use of the contraceptive pill. This phase is associated with a fall in progestogen levels, mucosal proliferation and keratinization. This subgroup often experiences remission during pregnancy. However, other studies report no correlation between aphthous stomatitis and menstrual period, pregnancy or menopause.

Aphthous stomatitis is uncommon in people who smoke. Tobacco use is associated with an increase in keratinization of the oral mucosa. In extreme forms, this may manifest as leukoplakia or stomatitis nicotina (smoker’s keratosis). This increased keratinization may mechanically reinforce the mucosa and reduce the tendency of ulcers to form after minor trauma, or present a more substantial barrier to microbes and antigens, but this is unclear. Nicotine is also known to stimulate production of adrenal steroids and reduce production of TNF-α, interleukin-1 and interleukin-6. Cessation of smoking is known to sometimes precede the onset of aphthous stomatitis in people previously unaffected, or exacerbate the condition in those who were already experiencing aphthous ulceration. Despite this correlation, starting smoking again does not usually lessen the condition.

Antigenic sensitivity

It has been hypothesized that the condition represents a state of heightened sensitivity to antigenic stimuli, with cross-reactivity of the resulting cell-mediated immune response with cells of the epithelium. Some hypothesize that aphthous stomatitis is caused by expression of HLA class II antigens along with the normally found HLA class I antigens in epithelial cells, which results in them being recognized by the immune system as foreign cells rather than self. Various antigenic triggers have been implicated as a trigger, including L forms of streptococci, herpes simplex virus, varicella-zoster virus, adenovirus, and cytomegalovirus.

Others argue that there is no available evidence that demonstrates that any of these organisms are capable of causing aphthous stomatitis by themselves. Some people with aphthous stomatitis may show herpes virus within the epithelium of the mucosa, but without any productive infection. In some persons, attacks of ulceration occur at the same time as asymptomatic viral shedding and elevated viral titres. However, antiviral medication has no effect on aphthous stomatitis.

In some instances, recurrent mouth ulcers may be a manifestation of an allergic reaction. Possible allergens include certain foods (e.g., chocolate, coffee, strawberries, eggs, nuts, tomatoes, cheese, citrus fruits, benzoates, cinnamaldehyde, and highly acidic foods), toothpastes, and mouthwashes. Where dietary allergens are responsible, mouth ulcers usually develop within about 12-24 hours of exposure.

Sodium lauryl sulphate (SLS), a detergent present in some brands of toothpaste and other oral healthcare products, may produce oral ulceration in some individuals. It has been shown that aphthous stomatitis is more common in people using toothpastes containing SLS, and that some reduction in ulceration occurs when a SLS-free toothpaste is used. Some have argued that since SLS is almost ubiquitously used in oral hygiene products, there is unlikely to be a true predisposition for aphthous stomatitis caused by SLS.

Systemic disease

Systemic disorders associated with aphthous-like ulceration
Behçet’s disease
Celiac disease
Cyclic neutropenia
Nutritional deficiencies
IgA deficiency
Immunocompromised states, e.g. HIV
Inflammatory bowel disease
MAGIC syndrome
PFAPA syndrome
Reiter’s disease
Sweet’s syndrome
Ulcus vulvae acutum

Aphthous-like ulceration may occur in association with several systemic disorders (see table). These ulcers are clinically and histopathologically identical to the lesions of aphthous stomatitis, but this type of oral ulceration is not considered to be true aphthous stomatitis by some sources. Some of these conditions may cause ulceration on other mucosal surfaces in addition to the mouth such as the conjunctiva or the genital mucous membranes. Resolution of the systemic condition often leads to decreased frequency and severity of the oral ulceration.

Behçet’s disease is a triad of mouth ulcers, genital ulcers and anterior uveitis. The main feature of Behçet’s disease is aphthous-like ulceration, but this is usually more severe than seen in aphthous stomatitis without a systemic cause, and typically resembles major or herpetiforme ulceration or both. Aphthous-like ulceration is the first sign of the disease in 25-75% of cases. Behçet’s is more common in individuals whose ethnic origin is from regions along the Silk Road (between the Mediterranean and the Far East). It tends to be rare in other countries such as the United States and the United Kingdom. MAGIC syndrome is a possible variant of Behçet disease, and is associated with aphthous-like ulceration. The name stands for “mouth and genital ulcers with inflamed cartilage” (relapsing polychondritis).

PFAPA syndrome is a rare condition that tends to occur in children. The name stands for “periodic fever, aphthae, pharyngitis (sore throat) and cervical adenitis” (inflammation of the lymph nodes in the neck). The fevers occur periodically about every 3-5 weeks. The condition appears to improve with tonsillectomy or immunosuppression, suggesting an immunologic cause.

In cyclic neutropenia, there is a reduction in the level of circulating neutrophils in the blood that occurs about every 21 days. Opportunistic infections commonly occur and aphthous-like ulceration is worst during this time.

Hematinic deficiencies (vitamin B12, folic acid and iron), occurring singly or in combination, and with or without any underlying gastrointestinal disease, may be twice as common in people with RAS. However, iron and vitamin supplements only infrequently improve the ulceration. The relationship to vitamin B12 deficiency has been the subject of many studies. Although these studies found that 0-42% of those with recurrent ulcers suffer from vitamin B12 deficiency, an association with deficiency is rare. Even in the absence of deficiency, vitamin B12 supplementation may be helpful due to unclear mechanisms. Hematinic deficiencies can cause anemia, which is also associated with aphthous-like ulceration.

Gastrointestinal disorders are sometimes associated with aphthous-like stomatitis, e.g. most commonly Celiac disease, but also inflammatory bowel disease such as Crohn’s disease or ulcerative colitis. The link between gastrointestinal disorders and aphthous stomatitis is probably related to nutritional deficiencies caused by malabsorption. Less than 5% of people with RAS have Celiac disease, which usually presents with severe malnutrition, anemia, abdominal pain, diarrhea and glossitis (inflammation of the tongue). Sometimes aphthous-like ulcerations can be the only sign of celiac disease. Despite this association, a gluten-free diet does not usually improve the oral ulceration.

Other examples of systemic conditions associated with aphthous-like ulceration include Reiter’s syndrome, and recurrent erythema multiforme.

DIAGNOSIS

Diagnosis is mostly based on the clinical appearance and the medical history. The most important diagnostic feature is a history of recurrent, self healing ulcers at fairly regular intervals. Although there are many causes of oral ulceration, recurrentoral ulceration has relatively few causes, most commonly aphthous stomatitis, but rarely Behçet’s disease, erythema multiforme, ulceration associated with gastrointestinal disease, and recurrent intra-oral herpes simplex infection. A systemic cause is more likely in adults who suddenly develop recurrent oral ulceration with no prior history.

Special investigations may be indicated to rule out other causes of oral ulceration. These include blood tests to exclude anemia, deficiencies of iron, folate or vitamin B12 or celiac disease. However, the nutritional deficiencies may be latent and the peripheral blood picture may appear relatively normal. Some suggest that screening for celiac disease should form part of the routine work up for individuals complaining of recurrent oral ulceration. Many of the systemic diseases cause other symptoms apart from oral ulceration, which is in contrast to aphthous stomatitis where there is isolated oral ulceration. Patch testing may be indicated if allergies are suspected (e.g. a strong relationship between certain foods and episodes of ulceration). Several drugs can cause oral ulceration (e.g. nicorandil), and a trial substitution to another drug may highlight a causal relationship.

Tissue biopsy is not usually required, unless to rule out other suspected conditions such as oral squamous cell carcinoma. The histopathologic appearance is not pathognomonic (the microscopic appearance is not specific to the condition). Early lesions have a central zone of ulceration covered by a fibrinous membrane. In the connective tissue deep to the ulcer there is increased vascularity and a mixed inflammatory infiltrate composed of lymphocytes, histiocytes and polymorphonuclear leukocytes. The epithelium on the margins of the ulcer shows spongiosis and there are many mononuclear cells in the basal third. There are also lymphocytes and histiocytes in the connective tissue surrounding deeper blood vessels near to the ulcer, described histologically as “perivascular cuffing”.

Classification

Aphthous stomatitis has been classified as a type of non-infectious stomatitis (inflammation of the mouth). One classification distinguishes “common simple aphthae”, accounting for 95% of cases, with 3-6 attacks per year, rapid healing, minimal pain and restriction of ulceration to the mouth; and “complex aphthae”, accounting for 5% of cases, where ulcers may be present on the genital mucosa in addition to mouth, healing is slower and pain is more severe. A more common method of classifying aphthous stomatitis is into three variants, distinguished by the size, number and location of the lesions, the healing time of individual ulcers and whether a scar is left after healing (see below).

Minor aphthous ulceration

This is the most common type of aphthous stomatitis, accounting for about 80-85% of all cases. This subtype is termed minor aphthous ulceration (MiAU), or minor recurrent aphthous stomatitis (MiRAS). The lesions themselves may be referred to as minor aphthae or minor aphthous ulcers. These lesions are generally less than 10& mm in diameter (usually about 2-3& mm), and affect non-keratinized mucosal surfaces (i.e. the labial and buccal mucosa, lateral borders of the tongue and the floor of the mouth). Usually several ulcers appear at the same time, but single ulcers are possible. Healing usually takes seven to ten days and leaves no scar. Between episodes of ulceration, there is usually an ulcer-free period of variable length.

Major aphthous ulceration

This subtype makes up about 10% of all cases of aphthous stomatitis. It is termed major aphthous ulceration (MaAU) or major recurrent aphthous stomatitis (MaRAS). Major aphthous ulcers (major aphthae) are similar to minor aphthous ulcers, but are more than 10& mm in diameter and the ulceration is deeper. Because the lesions are larger, healing takes longer (about twenty to thirty days), and may leave scars. Each episode of ulceration usually produces a greater number of ulcers, and the time between attacks is less than seen in minor aphthous stomatitis. Major aphthous ulceration usually affects non keratinized mucosal surfaces, but less commonly keratinized mucosa may also be involved, such as the dorsum (top surface) of the tongue or the gingiva (gums). The soft palate or the fauces (back of the throat) may also be involved, the latter being part of the oropharynx rather than the oral cavity. Compared to minor aphthous ulceration, major aphthae tend to have an irregular outline.

Herpetiform ulceration

Herpetiform ulcers, (also termed stomatitis herpetiformis, or herpes-like ulcerations) is a subtype of aphthous stomatitis so named because the lesions resemble a primary infection with herpes simplex virus (primary herpetic gingivostomatitis). However, herpetiform ulceration is not caused by herpes viruses. As with all types of aphthous stomatitis, it is not contagious. Unlike true herpetic ulcers, herpetiforme ulcers are not preceded by vesicles (small, fluid filled blisters). Herpetiforme ulcers are less than 1& mm in diameter and occur in variably sized crops up to one hundred at a time. Adjacent ulcers may merge to form larger, continuous areas of ulceration. Healing occurs within fifteen days without scarring. The ulceration may affect keratinized mucosal surfaces in addition to non keratinized. Herpetiform ulceration is often extremely painful, and the lesions recur more frequently than minor or major aphthous ulcers. Recurrence may be so frequent that ulceration is virtually continuous. It generally occurs in a slightly older age group than the other subtypes, and females are affected slightly more frequently than males.

RAS type ulceration

Recurrent oral ulceration associated with systemic conditions is termed “RAS type ulceration”, “RAS like ulceration”, or “aphthous-like ulcers”. Aphthous stomatitis occurs in individuals with no associated systemic disease. Persons with certain systemic diseases may be prone to oral ulceration, but this is secondary to the underlying medical condition (see the systemic disease section). This kind of ulceration is considered by some to be separate from true aphthous stomatitis. However, this definition is not strictly applied. For example, many sources refer to oral ulceration caused by anemia and/or nutritional deficiencies as aphthous stomatitis, and some also consider Behçet’s disease to be a variant.

TREATMENT

The vast majority of people with aphthous stomatitis have minor symptoms and do not require any specific therapy. The pain is often tolerable with simple dietary modification during an episode of ulceration such as avoiding spicy or acidic foods and beverages. Many different topical and systemic medications have been proposed (see table), sometimes showing little or no evidence of efficacy when formally investigated. Some of the results of interventions for RAS may in truth represent a placebo effect. No therapy is curative, with treatment aiming to relieve pain, promote healing and reduce the frequency of episodes of ulceration.

Pharmacotherapies used in aphthous stomatitis
Drug type Intended action Example(s)
Topical covering agents / barriers Reduce pain Orabase (often combined with triamcinolone).
Topical analgesics / anesthetics / anti-inflammatory agents Reduce pain Benzydamine hydrochloride mouthwash or spray, Amlexanox paste, viscous lidocaine, diclofenac in hyaluronan.
Topical antiseptics Hasten healing (prevent secondary infection) Doxycycline, tetracycline, minocycline, chlorhexidine gluconate, triclosan.
Topical mild potency corticosteroids Reduce inflammation Hydrocortisone sodium succinate.
Topical moderate potency corticosteroids Reduce inflammation Beclomethasone dipropionate aerosol, fluocinonide, clobetasol, betamethasone sodium phosphate, dexamethasone.
Orally administered drugs Various, mostly modulating immune response Prednisolone, colchicine, pentoxifylline, azathioprine, thalidomide, dapsone, mycophenolate mofetil, adalimumab, vitamin B12, Clofazimine, Levamisole, Montelukast, Sulodexide, levamisole.

The first line therapy for aphthous stomatitis is topical agents rather than systemic medication, with topical corticosteroids being the mainstay treatment. Systemic treatment is usually reserved for severe disease due to the risk of adverse side effects associated with many of these agents. A systematic review found that no single systemic intervention was found to be effective. Good oral hygiene is also important to prevent secondary infection of the ulcers.

Occasionally, in females where ulceration is correlated to the menstrual cycle or to an oral contraceptive, progestogen or a change in oral contraceptive may be beneficial. Use of nicotine replacement therapy for people who have developed oral ulceration after stopping smoking has also been reported. Starting smoking again does not usually lessen the condition. Trauma can be reduced by avoiding rough or sharp foodstuffs and by brushing teeth with care. If sodium lauryl sulfate is suspected to be the cause, avoidance of products containing this chemical may be useful and prevent recurrence in some individuals. Similarly patch testing may indicate that food allergy is responsible, and the diet modified accordingly. If investigations reveal deficiency states, correction of the deficiency may result in resolution of the ulceration. For example, there is some evidence that vitamin B12 supplementation may prevent recurrence in some individuals.

Surgical excision of aphthous ulcers has been described, but it is an ineffective and inappropriate treatment. Silver nitrate has also been used as a chemical cauterant. Apart from the mainstream approaches detailed above, there are numerous treatments of unproven effectiveness, ranging from herbal remedies to otherwise alternative treatments, including aloe vera, myrtus communis, Rosa damascena, zinc sulfate, nicotine, polio virus vaccine and prostaglandin E2.

SUMMARY

Aphthous stomatitis (also termedrecurrent aphthous stomatitisrecurring oral aphthae or recurrent aphthous ulceration) is a common condition characterized by the repeated formation of benign and non-contagious mouth ulcers (aphthae), in otherwise healthy individuals. The informal term canker sores is also used, mainly in North America.

The cause is not completely understood, but involves a T cell-mediated immune response triggered by a variety of factors. Individuals vary in their observed triggers, which may include nutritional deficiencies, local trauma, stress, hormonal influences, allergies, genetic predisposition and other factors.

These ulcers occur periodically and heal completely between attacks. In the majority of cases, the individual ulcers last about 7-10 days, and ulceration episodes occur 3-6 times per year. Most appear on the non-keratinizing epithelial surfaces in the mouth (i.e. anywhere except the attached gingiva, the hard palate and the dorsum of the tongue), although the more severe forms, which are less common, may also involve keratinizing epithelial surfaces. Symptoms range from a minor nuisance to interfering with eating and drinking. The severe forms may be debilitating, even causing weight loss due to malnutrition.

The condition is very common, affecting about 20% of the general population to some degree. The onset is often during childhood or adolescence, and the condition usually lasts for several years before gradually disappearing. There is no cure, and treatments aim to manage pain, promote healing and reduce the frequency of episodes of ulceration.

CAUSES

The cause is not entirely clear, but is thought to be multifactorial. It has even been suggested that aphthous stomatitis is not a single entity but rather a group of conditions with different causes. Multiple research studies have attempted to identify a causative organism, but aphthous stomatitis appears to be non-contagious, non-infectious and not sexually transmissible. The mucosal destruction is thought to be the result of a T cell (T lymphocyte) mediated immune response which involves the generation of interleukins and tumor necrosis factor alpha (TNF-α). Mast cells and macrophages are also involved, secreting TNF-α along with the T cells. When early aphthous ulcers are biopsied, the histologic appearance shows a dense inflammatory infiltrate, 80% of which is made up of T cells. Persons with aphthous stomatitis have circulating lymphocytes which react with peptides 91-105 of heat shock protein 65-60. Furthermore, the ratio of CD4+ T cells to CD8+ T cells in the peripheral blood of individuals with aphthous stomatitis is decreased.

Despite this preferred theory of immuno-dysregulation held by most researchers, aphthous stomatitis behaves dis-similarly to autoimmune diseases in many regards. There is no association between aphthous stomatitis and other autoimmune diseases, which often accompany each other; common autoantibodies are not detected, the condition tends to resolve spontaneously with advancing age rather than worsen, and usually serum immunoglobulins are at normal levels.

Evidence for the T cell-mediated mechanism of mucosal destruction is strong, but the exact triggers for this process are unknown and are thought to be multiple and varied from one person to the next. This suggests that there are a number of possible triggers, each of which is capable of producing the disease in different subgroups. In other words, different subgroups of individuals with aphthous stomatitis appear to have different causes for the condition. These sub-groups have been considered to be in three general groups, namely primary immuno-dysregulation, decrease of the mucosal barrier and states of heightened antigenic sensitivity. Etiologic factors in aphthous stomatitis are also sometimes considered in 2 categories, host-related or environmental.

Immunity

At least 40% of people with aphthous stomatitis have a positive family history, suggesting that some people are genetically predisposed to suffering with oral ulceration. HLA-B12, HLA-B51, HLA-Cw7, HLA-A2, HLA-A11, and HLA-DR2 are examples of human leukocyte antigen types associated with aphthous stomatitis. However, these HLA types are inconsistently associated with the condition, and also vary according to ethnicity. People who have a positive family history of aphthous stomatitis tend to develop a more severe form of the condition, and at an earlier age than is typical.

Stress has effects on the immune system, which may explain why some cases directly correlate with stress. It is often stated that ulceration is exacerbated during examination periods and lessened during periods of vacation. Alternatively, it has been suggested that oral parafunctional activities such as lip or cheek chewing become more pronounced during periods of stress, and hence the mucosa is subjected to more minor trauma.

Aphthous-like ulceration also occurs in conditions involving systemic immuno-dysregulation, e.g. cyclic neutropenia and human immunodeficiency virus infection. In cyclic neutropenia, more severe oral ulceration occurs during periods of severe immuno-dysregulation, and resolution of the underlying neutropenia prevents the cycle of ulceration. The relative increase in percentage of CD8+ T cells, caused by a reduction in numbers of CD4+ T cells may be implicated in RAS-type ulceration in HIV infection.

Mucosal barrier

The thickness of the mucosa may be an important factor in aphthous stomatitis. Usually, ulcers form on non keratinizing mucosal surfaces in the mouth. Factors which decrease the thickness of mucosa increase the frequency of occurrence, and factors which increase the thickness of the mucosa correlate with decreased ulceration.

The nutritional deficiencies associated with aphthous stomatitis (B12, folate, and iron) can all cause a decrease in the thickness of the oral mucosa (atrophy).

Local trauma is also associated with aphthous stomatitis, and it is known that trauma can decrease the mucosal barrier. Trauma could occur during injections of local anesthetic in the mouth, or otherwise during dental treatments, frictional trauma from a sharp surface in the mouth such as broken tooth, or from tooth brushing.

Hormonal factors are capable of altering the mucosal barrier. In one study, a small group of females with apthous stomatitis had fewer occurrences of aphthous ulcers during the luteal phase of the menstrual cycle or with use of the contraceptive pill. This phase is associated with a fall in progestogen levels, mucosal proliferation and keratinization. This subgroup often experiences remission during pregnancy. However, other studies report no correlation between aphthous stomatitis and menstrual period, pregnancy or menopause.

Aphthous stomatitis is uncommon in people who smoke. Tobacco use is associated with an increase in keratinization of the oral mucosa. In extreme forms, this may manifest as leukoplakia or stomatitis nicotina (smoker’s keratosis). This increased keratinization may mechanically reinforce the mucosa and reduce the tendency of ulcers to form after minor trauma, or present a more substantial barrier to microbes and antigens, but this is unclear. Nicotine is also known to stimulate production of adrenal steroids and reduce production of TNF-α, interleukin-1 and interleukin-6. Cessation of smoking is known to sometimes precede the onset of aphthous stomatitis in people previously unaffected, or exacerbate the condition in those who were already experiencing aphthous ulceration. Despite this correlation, starting smoking again does not usually lessen the condition.

Antigenic sensitivity

It has been hypothesized that the condition represents a state of heightened sensitivity to antigenic stimuli, with cross-reactivity of the resulting cell-mediated immune response with cells of the epithelium. Some hypothesize that aphthous stomatitis is caused by expression of HLA class II antigens along with the normally found HLA class I antigens in epithelial cells, which results in them being recognized by the immune system as foreign cells rather than self. Various antigenic triggers have been implicated as a trigger, including L forms of streptococci, herpes simplex virus, varicella-zoster virus, adenovirus, and cytomegalovirus.

Others argue that there is no available evidence that demonstrates that any of these organisms are capable of causing aphthous stomatitis by themselves. Some people with aphthous stomatitis may show herpes virus within the epithelium of the mucosa, but without any productive infection. In some persons, attacks of ulceration occur at the same time as asymptomatic viral shedding and elevated viral titres. However, antiviral medication has no effect on aphthous stomatitis.

In some instances, recurrent mouth ulcers may be a manifestation of an allergic reaction. Possible allergens include certain foods (e.g., chocolate, coffee, strawberries, eggs, nuts, tomatoes, cheese, citrus fruits, benzoates, cinnamaldehyde, and highly acidic foods), toothpastes, and mouthwashes. Where dietary allergens are responsible, mouth ulcers usually develop within about 12-24 hours of exposure.

Sodium lauryl sulphate (SLS), a detergent present in some brands of toothpaste and other oral healthcare products, may produce oral ulceration in some individuals. It has been shown that aphthous stomatitis is more common in people using toothpastes containing SLS, and that some reduction in ulceration occurs when a SLS-free toothpaste is used. Some have argued that since SLS is almost ubiquitously used in oral hygiene products, there is unlikely to be a true predisposition for aphthous stomatitis caused by SLS.

Systemic disease

Systemic disorders associated with aphthous-like ulceration
Behçet’s disease
Celiac disease
Cyclic neutropenia
Nutritional deficiencies
IgA deficiency
Immunocompromised states, e.g. HIV
Inflammatory bowel disease
MAGIC syndrome
PFAPA syndrome
Reiter’s disease
Sweet’s syndrome
Ulcus vulvae acutum

Aphthous-like ulceration may occur in association with several systemic disorders (see table). These ulcers are clinically and histopathologically identical to the lesions of aphthous stomatitis, but this type of oral ulceration is not considered to be true aphthous stomatitis by some sources. Some of these conditions may cause ulceration on other mucosal surfaces in addition to the mouth such as the conjunctiva or the genital mucous membranes. Resolution of the systemic condition often leads to decreased frequency and severity of the oral ulceration.

Behçet’s disease is a triad of mouth ulcers, genital ulcers and anterior uveitis. The main feature of Behçet’s disease is aphthous-like ulceration, but this is usually more severe than seen in aphthous stomatitis without a systemic cause, and typically resembles major or herpetiforme ulceration or both. Aphthous-like ulceration is the first sign of the disease in 25-75% of cases. Behçet’s is more common in individuals whose ethnic origin is from regions along the Silk Road (between the Mediterranean and the Far East). It tends to be rare in other countries such as the United States and the United Kingdom. MAGIC syndrome is a possible variant of Behçet disease, and is associated with aphthous-like ulceration. The name stands for “mouth and genital ulcers with inflamed cartilage” (relapsing polychondritis).

PFAPA syndrome is a rare condition that tends to occur in children. The name stands for “periodic fever, aphthae, pharyngitis (sore throat) and cervical adenitis” (inflammation of the lymph nodes in the neck). The fevers occur periodically about every 3-5 weeks. The condition appears to improve with tonsillectomy or immunosuppression, suggesting an immunologic cause.

In cyclic neutropenia, there is a reduction in the level of circulating neutrophils in the blood that occurs about every 21 days. Opportunistic infections commonly occur and aphthous-like ulceration is worst during this time.

Hematinic deficiencies (vitamin B12, folic acid and iron), occurring singly or in combination, and with or without any underlying gastrointestinal disease, may be twice as common in people with RAS. However, iron and vitamin supplements only infrequently improve the ulceration. The relationship to vitamin B12 deficiency has been the subject of many studies. Although these studies found that 0-42% of those with recurrent ulcers suffer from vitamin B12 deficiency, an association with deficiency is rare. Even in the absence of deficiency, vitamin B12 supplementation may be helpful due to unclear mechanisms. Hematinic deficiencies can cause anemia, which is also associated with aphthous-like ulceration.

Gastrointestinal disorders are sometimes associated with aphthous-like stomatitis, e.g. most commonly Celiac disease, but also inflammatory bowel disease such as Crohn’s disease or ulcerative colitis. The link between gastrointestinal disorders and aphthous stomatitis is probably related to nutritional deficiencies caused by malabsorption. Less than 5% of people with RAS have Celiac disease, which usually presents with severe malnutrition, anemia, abdominal pain, diarrhea and glossitis (inflammation of the tongue). Sometimes aphthous-like ulcerations can be the only sign of celiac disease. Despite this association, a gluten-free diet does not usually improve the oral ulceration.

Other examples of systemic conditions associated with aphthous-like ulceration include Reiter’s syndrome, and recurrent erythema multiforme.

DIAGNOSIS

Diagnosis is mostly based on the clinical appearance and the medical history. The most important diagnostic feature is a history of recurrent, self healing ulcers at fairly regular intervals. Although there are many causes of oral ulceration, recurrentoral ulceration has relatively few causes, most commonly aphthous stomatitis, but rarely Behçet’s disease, erythema multiforme, ulceration associated with gastrointestinal disease, and recurrent intra-oral herpes simplex infection. A systemic cause is more likely in adults who suddenly develop recurrent oral ulceration with no prior history.

Special investigations may be indicated to rule out other causes of oral ulceration. These include blood tests to exclude anemia, deficiencies of iron, folate or vitamin B12 or celiac disease. However, the nutritional deficiencies may be latent and the peripheral blood picture may appear relatively normal. Some suggest that screening for celiac disease should form part of the routine work up for individuals complaining of recurrent oral ulceration. Many of the systemic diseases cause other symptoms apart from oral ulceration, which is in contrast to aphthous stomatitis where there is isolated oral ulceration. Patch testing may be indicated if allergies are suspected (e.g. a strong relationship between certain foods and episodes of ulceration). Several drugs can cause oral ulceration (e.g. nicorandil), and a trial substitution to another drug may highlight a causal relationship.

Tissue biopsy is not usually required, unless to rule out other suspected conditions such as oral squamous cell carcinoma. The histopathologic appearance is not pathognomonic (the microscopic appearance is not specific to the condition). Early lesions have a central zone of ulceration covered by a fibrinous membrane. In the connective tissue deep to the ulcer there is increased vascularity and a mixed inflammatory infiltrate composed of lymphocytes, histiocytes and polymorphonuclear leukocytes. The epithelium on the margins of the ulcer shows spongiosis and there are many mononuclear cells in the basal third. There are also lymphocytes and histiocytes in the connective tissue surrounding deeper blood vessels near to the ulcer, described histologically as “perivascular cuffing”.

Classification

Aphthous stomatitis has been classified as a type of non-infectious stomatitis (inflammation of the mouth). One classification distinguishes “common simple aphthae”, accounting for 95% of cases, with 3-6 attacks per year, rapid healing, minimal pain and restriction of ulceration to the mouth; and “complex aphthae”, accounting for 5% of cases, where ulcers may be present on the genital mucosa in addition to mouth, healing is slower and pain is more severe. A more common method of classifying aphthous stomatitis is into three variants, distinguished by the size, number and location of the lesions, the healing time of individual ulcers and whether a scar is left after healing (see below).

Minor aphthous ulceration

This is the most common type of aphthous stomatitis, accounting for about 80-85% of all cases. This subtype is termed minor aphthous ulceration (MiAU), or minor recurrent aphthous stomatitis (MiRAS). The lesions themselves may be referred to as minor aphthae or minor aphthous ulcers. These lesions are generally less than 10& mm in diameter (usually about 2-3& mm), and affect non-keratinized mucosal surfaces (i.e. the labial and buccal mucosa, lateral borders of the tongue and the floor of the mouth). Usually several ulcers appear at the same time, but single ulcers are possible. Healing usually takes seven to ten days and leaves no scar. Between episodes of ulceration, there is usually an ulcer-free period of variable length.

Major aphthous ulceration

This subtype makes up about 10% of all cases of aphthous stomatitis. It is termed major aphthous ulceration (MaAU) or major recurrent aphthous stomatitis (MaRAS). Major aphthous ulcers (major aphthae) are similar to minor aphthous ulcers, but are more than 10& mm in diameter and the ulceration is deeper. Because the lesions are larger, healing takes longer (about twenty to thirty days), and may leave scars. Each episode of ulceration usually produces a greater number of ulcers, and the time between attacks is less than seen in minor aphthous stomatitis. Major aphthous ulceration usually affects non keratinized mucosal surfaces, but less commonly keratinized mucosa may also be involved, such as the dorsum (top surface) of the tongue or the gingiva (gums). The soft palate or the fauces (back of the throat) may also be involved, the latter being part of the oropharynx rather than the oral cavity. Compared to minor aphthous ulceration, major aphthae tend to have an irregular outline.

Herpetiform ulceration

Herpetiform ulcers, (also termed stomatitis herpetiformis, or herpes-like ulcerations) is a subtype of aphthous stomatitis so named because the lesions resemble a primary infection with herpes simplex virus (primary herpetic gingivostomatitis). However, herpetiform ulceration is not caused by herpes viruses. As with all types of aphthous stomatitis, it is not contagious. Unlike true herpetic ulcers, herpetiforme ulcers are not preceded by vesicles (small, fluid filled blisters). Herpetiforme ulcers are less than 1& mm in diameter and occur in variably sized crops up to one hundred at a time. Adjacent ulcers may merge to form larger, continuous areas of ulceration. Healing occurs within fifteen days without scarring. The ulceration may affect keratinized mucosal surfaces in addition to non keratinized. Herpetiform ulceration is often extremely painful, and the lesions recur more frequently than minor or major aphthous ulcers. Recurrence may be so frequent that ulceration is virtually continuous. It generally occurs in a slightly older age group than the other subtypes, and females are affected slightly more frequently than males.

RAS type ulceration

Recurrent oral ulceration associated with systemic conditions is termed “RAS type ulceration”, “RAS like ulceration”, or “aphthous-like ulcers”. Aphthous stomatitis occurs in individuals with no associated systemic disease. Persons with certain systemic diseases may be prone to oral ulceration, but this is secondary to the underlying medical condition (see the systemic disease section). This kind of ulceration is considered by some to be separate from true aphthous stomatitis. However, this definition is not strictly applied. For example, many sources refer to oral ulceration caused by anemia and/or nutritional deficiencies as aphthous stomatitis, and some also consider Behçet’s disease to be a variant.

TREATMENT

The vast majority of people with aphthous stomatitis have minor symptoms and do not require any specific therapy. The pain is often tolerable with simple dietary modification during an episode of ulceration such as avoiding spicy or acidic foods and beverages. Many different topical and systemic medications have been proposed (see table), sometimes showing little or no evidence of efficacy when formally investigated. Some of the results of interventions for RAS may in truth represent a placebo effect. No therapy is curative, with treatment aiming to relieve pain, promote healing and reduce the frequency of episodes of ulceration.

Pharmacotherapies used in aphthous stomatitis
Drug type Intended action Example(s)
Topical covering agents / barriers Reduce pain Orabase (often combined with triamcinolone).
Topical analgesics / anesthetics / anti-inflammatory agents Reduce pain Benzydamine hydrochloride mouthwash or spray, Amlexanox paste, viscous lidocaine, diclofenac in hyaluronan.
Topical antiseptics Hasten healing (prevent secondary infection) Doxycycline, tetracycline, minocycline, chlorhexidine gluconate, triclosan.
Topical mild potency corticosteroids Reduce inflammation Hydrocortisone sodium succinate.
Topical moderate potency corticosteroids Reduce inflammation Beclomethasone dipropionate aerosol, fluocinonide, clobetasol, betamethasone sodium phosphate, dexamethasone.
Orally administered drugs Various, mostly modulating immune response Prednisolone, colchicine, pentoxifylline, azathioprine, thalidomide, dapsone, mycophenolate mofetil, adalimumab, vitamin B12, Clofazimine, Levamisole, Montelukast, Sulodexide, levamisole.

The first line therapy for aphthous stomatitis is topical agents rather than systemic medication, with topical corticosteroids being the mainstay treatment. Systemic treatment is usually reserved for severe disease due to the risk of adverse side effects associated with many of these agents. A systematic review found that no single systemic intervention was found to be effective. Good oral hygiene is also important to prevent secondary infection of the ulcers.

Occasionally, in females where ulceration is correlated to the menstrual cycle or to an oral contraceptive, progestogen or a change in oral contraceptive may be beneficial. Use of nicotine replacement therapy for people who have developed oral ulceration after stopping smoking has also been reported. Starting smoking again does not usually lessen the condition. Trauma can be reduced by avoiding rough or sharp foodstuffs and by brushing teeth with care. If sodium lauryl sulfate is suspected to be the cause, avoidance of products containing this chemical may be useful and prevent recurrence in some individuals. Similarly patch testing may indicate that food allergy is responsible, and the diet modified accordingly. If investigations reveal deficiency states, correction of the deficiency may result in resolution of the ulceration. For example, there is some evidence that vitamin B12 supplementation may prevent recurrence in some individuals.

Surgical excision of aphthous ulcers has been described, but it is an ineffective and inappropriate treatment. Silver nitrate has also been used as a chemical cauterant. Apart from the mainstream approaches detailed above, there are numerous treatments of unproven effectiveness, ranging from herbal remedies to otherwise alternative treatments, including aloe vera, myrtus communis, Rosa damascena, zinc sulfate, nicotine, polio virus vaccine and prostaglandin E2.

EPIDEMIOLOGY

Reported prevalence ranges from 5-66%, but in most populations, about 20% of individuals are affected to some degree, making it the most common disease of the oral mucosa. Aphthous stomatitis occurs worldwide, but is more common in developed countries.

Within nations, there is a slightly higher prevalence in higher socioeconomic groups. Males and females are affected in an equal ratio, and the peak age of onset between 10 and 19 years. About 80% of people with aphthous stomatitis first developed the condition before the age of 30. There have been reports of ethnic variation. For example, in the United States, aphthous stomatitis may be three times more common in white-skinned people than black-skinned people.

SIGNS AND SYMPTOMS

Persons with aphthous stomatitis have no detectable systemic symptoms or signs (i.e., outside the mouth). Generally, symptoms may include prodromal sensations such as burning, itching, or stinging, which may precede the appearance of any lesion by some hours; and pain, which is often out of proportion to the extent of the ulceration and is worsened by physical contact, especially with certain foods and drinks (e.g., acidic). Pain is worst in the days immediately following the initial formation of the ulcer, and then recedes as healing progresses. If there are lesions on the tongue, speaking and chewing can be uncomfortable, and ulcers on the soft palate, oropharynx, or esophagus can cause odynophagia (painful swallowing). Signs are limited to the lesions themselves.

Ulceration episodes usually occur about 3-6 times per year. However severe disease is characterized by virtually constant ulceration (new lesions developing before old ones have healed), and may cause debilitating chronic pain and interfere with comfortable eating. In severe cases, this prevents adequate nutrient intake, leading to malnutrition and weight loss.

Aphthous ulcers typically begin as erythematous macules (reddened, flat area of mucosa) which develop into ulcers that are covered with a yellow-grey fibrinous membrane that can be scraped away. An erythematous “halo” surrounds the ulcer. The size, number, location, healing time, and periodicity between episodes of ulcer formation are all dependent upon the subtype of aphthous stomatitis.

PROGNOSIS

By definition, there is no serious underlying medical condition, and importantly the ulcers do not represent oral cancer and they are not infectious. However, aphthae are capable of causing significant discomfort. There is a spectrum of severity, with symptoms ranging from a minor nuisance to disabling. Due to pain during eating, weight loss may develop as a result of severe aphthous stomatitis. Usually, the condition lasts for several years before spontaneously disappearing in later life.

HISTORY SOCIETY AND CULTURE

“Aphthous affectations” and “aphthous ulcerations” of the mouth are mentioned several times in the treatise “Of the Epidemics” (part of the Hippocratic corpus, in the 4th century B.C), although it seems likely that this was oral ulceration as a manifestation of some infectious disease, since they are described as occurring in epidemic-like patterns, with concurrent symptoms such as fever.

Aphthous stomatitis was once thought to be a form of recurrent herpes simplex virus infection, and some clinicians still refer to the condition as “herpes” despite this etiology having been disproven.

The informal term “canker sore” is sometimes used, mainly in North America, either to describe this condition generally, or to refer to the individual ulcers of this condition, or mouth ulcers of any cause unrelated to this condition. The origin of the word “canker” is thought to have been influenced by Latin, Old English, Middle English and Old North French. In Latin,cancer translates to “malignant tumor” or literally “crab” (related to the likening of sectioned tumors to the limbs of a crab). The closely related word in Middle English and Old North French, chancre, now more usually applied to syphilis, is also thought to be involved. Despite this etymology, aphthous stomatitis is not a form of cancer but rather entirely benign.

An aphtha (plural aphthae) is a non specific term that refers to an ulcer of the mouth. The word is derived from the Greek word aphtha meaning “eruption” or “ulcer”. The lesions of several other oral conditions are sometimes described as aphthae, including Bednar’s aphthae (infected, traumatic ulcers on the hard palate in infants), oral candidiasis, and foot-and-mouth disease. When used without qualification, aphthae commonly refers to lesions of recurrent aphthous stomatitis. Since the word aphtha is often taken to be synonymous with ulcer, it has been suggested that the term “aphthous ulcer” is redundant, but it remains in common use. Stomatitis is also a non-specific term referring to any inflammatory process in the mouth, with or without oral ulceration. It may describe many different conditions apart from aphthous stomatitis such as angular stomatitis.

The current most widely used medical term is “recurrent aphthous stomatitis” or simply “aphthous stomatitis”. Historically, many different terms have been used to refer to recurrent aphthous stomatitis or its sub-types, and some are still in use. Mikulicz’ aphthae is a synonym of minor RAS, named after Jan Mikulicz-Radecki. Synonyms for major RAS include Sutton’s ulcers (named after Richard Lightburn Sutton), Sutton’s disease, Sutton’s syndrome and pariadenitis mucosa necrotica recurrens. Synonyms for aphthous stomatitis as a whole include (recurrent) oral aphthae, (recurrent) aphthous ulceration and (oral) aphthosis.

In traditional Chinese medicine, treatments for aphthae focus on clearing heat and nourishing Yin.

Rembrandt Gentle White toothpaste did not contain SLS and was specifically marketed as being for the benefit of “canker sore sufferers”. When the manufacturer Johnson & Johnson discontinued the product in 2014, it caused a backlash of anger from long term customers, and the toothpaste began to sell for many times the original price on the auction website ebay.


Hair loss or baldness (technically known as alopecia) is a loss of hair from the head or body. Baldness can refer to general hair loss or androgenic alopecia (male pattern baldness). Some types of baldness can be caused by alopecia areata, an autoimmune disorder. The extreme forms of alopecia areata are alopecia totalis, which involves the loss of all head hair, and alopecia universalis, which involves the loss of all hair from the head and the body.

Baldness and hypotrichosis can have many causes, including fungal infection (tinea capitis), traumatic damage, such as by compulsive pulling (trichotillomania), as a result of radiotherapy or chemotherapy, and as a result of nutritional deficiencies such as iron, and as a result of autoimmune phenomena, including alopecia areata and hair loss associated with systemic lupus erythematosus.

CAUSES

Although not completely understood, alopecia can have many causes:

Male pattern hair loss

More than 95% of hair thinning in men is male pattern hair loss (also known as male pattern baldness). Male pattern hair loss is characterized by hair receding from the lateral sides of the forehead (known as a “receding hairline”) and/or a thinning crown (balding to the area known as the ‘vertex’). Both become more pronounced until they eventually meet, leaving a horseshoe-shaped ring of hair around the back of the head.

The incidence of pattern baldness varies from population to population and is based on genetic background. Environmental factors do not seem to affect this type of baldness greatly. One large scale study in Maryborough, Victoria, Australia showed the prevalence of mid-frontal baldness increases with age and affects 73.5 percent of men and 57 percent of women aged 80 and over. A rough rule of thumb is that the incidence of baldness in males corresponds to chronological age. For example, according to Medem Medical Library’s website, male pattern baldness (MPB) affects roughly 40& million men in the United States. Approximately 25 percent of men begin balding by age 30; two-thirds begin balding by age 60.

There is a 4 in 7 chance of receiving the baldness gene. Onset of hair loss sometimes begins as early as the end of puberty, and is mostly genetically determined. It was previously believed that baldness was inherited from the maternal grandfather. While there is some basis for this belief, both parents contribute to their offspring’s likelihood of hair loss. Most likely, inheritance involves many genes with variable penetrance.

The trigger for this type of baldness is dihydrotestosterone, a more-potent form of testosterone often referred to by its acronym DHT. DHT is an androgenic hormone, body- and facial-hair growth promoter that can adversely affect the prostate as well as the hair located on the head. The mechanism by which DHT accomplishes this is not yet fully understood. In genetically prone scalps (i.e., those experiencing male or female pattern baldness), DHT initiates a process of follicular miniaturization, in which the hair follicle begins to deteriorate. As a consequence, the hair’s growth phase (anagen) is shortened, and young, unpigmented vellus hair is prevented from growing and maturing into the deeply rooted and pigmented terminal hair that makes up 90 percent of the hair on the head. In time, hair becomes thinner, and its overall volume is reduced so that it resembles fragile vellus hair or “peach fuzz” until, finally, the follicle goes dormant and ceases producing hair completely.

Nutrition

Studies have shown that poor nutrition, limited food intake, and deficiencies in certain nutrients can cause thinning. These include deficiencies of biotin, protein, zinc and poor human iron metabolism, although complete baldness is not usually seen. A diet high in animal fats (often found in fast food) and vitamin A is also thought to lead to hair loss.

Hypervitaminosis A
Iron deficiency or malnutrition in general
Infection

Dissecting cellulitis
Fungal infections (such as tinea capitis)
Tinea capitis
Folliculitis
Secondary syphilis
Demodex folliculorum, a microscopic mite that feeds on the sebum produced by the sebaceous glands, denies hair essential nutrients and can cause thinning. Demodex folliculorum is not present on every scalp and is more likely to live in an excessively oily scalp environment.
Drugs

Temporary or permanent hair loss can be caused by several medications, including those for blood pressure problems, diabetes, heart disease and cholesterol. Any that affect the body’s hormone balance can have a pronounced effect: these include the contraceptive pill, hormone replacement therapy, steroids and acne medications.
Medications (side effects from drugs, including chemotherapy, anabolic steroids, and birth control pills in which a large number of hairs enter the resting phase at the same time, causing shedding and subsequent thinning. The condition also presents as a side effect of chemotherapy – while targeting dividing cancer cells, this treatment also affects hair’s growth phase with the result that almost 90% of hairs fall out soon after chemotherapy starts.
Radiation to the scalp, as when radiotherapy is applied to the head for the treatment of certain cancers there, can cause baldness of the irradiated areas.
Pregnancy

Hair loss often follows childbirth without causing baldness. In this situation, the hair is actually thicker during pregnancy due to increased circulating oestrogens. After the baby is born, the oestrogen levels fall back to normal prepregnancy levels, and the additional hair foliage drops out. A similar situation occurs in women taking the fertility-stimulating drug clomiphene.

Other

Air and water pollutants as well as minerals in water and the phototoxic effects of sunlight can cause thinning by aging the scalp skin and damaging hair.
Alopecia areata is an autoimmune disorder also known as “spot baldness” that can result in hair loss ranging from just one location (Alopecia areata monolocularis) to every hair on the entire body (Alopecia areata universalis). Although thought to be caused by hair follicles becoming dormant, what triggers alopecia areata is not known. In most cases the condition corrects itself, but it can also spread to the entire scalp (alopecia totalis) or to the entire body (alopecia universalis).
Localized or diffuse hair loss may also occur in cicatricial alopecia (lupus erythematosus, lichen plano pilaris, folliculitis decalvans, central centrifugal cicatricial alopecia, postmenopausal frontal fibrosing alopecia, etc.). Tumours and skin outgrowths also induce localized baldness (sebaceous nevus, basal cell carcinoma, squamous cell carcinoma).
Hypothyroidism (an under-active thyroid) and the side effects of its related medications can cause hair loss, typically frontal, which is particularly associated with thinning of the outer third of the eyebrows (also seen with syphilis). Hyperthyroidism (an over-active thyroid) can also cause hair loss, which is parietal rather than frontal.
Temporary loss of hair can occur in areas where sebaceous cysts are present for considerable duration (normally one to several weeks).
Congenital triangular alopecia – It is a triangular, or oval in some cases, shaped patch of hair loss in the temple area of the scalp that occurs mostly in young children. The affected area mainly contains vellus hair follicles or no hair follicles at all, but it does not expand. Its causes are unknown, and although it is a permanent condition, it does not have any other effect on the affected individuals.
Gradual thinning of hair with age is a natural condition known as involutional alopecia. This is caused by an increasing number of hair follicles switching from the growth, or anagen, phase into a resting phase, or telogen phase, so that remaining hairs become shorter and fewer in number.
An unhealthy scalp environment can play a significant role in hair thinning by contributing to miniaturization or causing damage. Air and water pollutants, environmental toxins, conventional styling products and excessive amounts of sebum have the potential to build up on the scalp. This debris can block hair follicles and cause their deterioration and consequent miniaturization of hair. It can also physically restrict hair growth or damage the hair cuticle, leading to hair that is weakened and easily broken off before its natural lifecycle has ended.
Causes of alopecia include:

Alopecia mucinosa
Biotinidase deficiency
Chronic inflammation
Diabetes
Hair treatments (chemicals in relaxers, hair straighteners)
Lupus erythematosus
Pseudopelade of Brocq
Telogen effluvium
Tufted folliculitis
DIAGNOSIS

Because they are not usually associated with an increased loss rate, male-pattern and female-pattern hair loss do not generally require testing. If hair loss occurs in a young man with no family history, drug use could be the cause.

The pull test helps to evaluate diffuse scalp hair loss. Gentle traction is exerted on a group of hairs (about 40-60) on three different areas of the scalp. The number of extracted hairs is counted and examined under a microscope. Normally, fewer than three hairs per area should come out with each pull. If more than ten hairs are obtained, the pull test is considered positive.
The pluck test is conducted by pulling hair out “by the roots”. The root of the plucked hair is examined under a microscope to determine the phase of growth, and is used to diagnose a defect of telogen, anagen, or systemic disease. Telogen hairs have tiny bulbs without sheaths at their roots. Telogen effluvium shows an increased percentage of hairs upon examination. Anagen hairs have sheaths attached to their roots. Anagen effluvium shows a decrease in telogen-phase hairs and an increased number of broken hairs.
Scalp biopsy is used when the diagnosis is unsure; a biopsy allows for differing between scarring and nonscarring forms. Hair samples are taken from areas of inflammation, usually around the border of the bald patch.
Daily hair counts are normally done when the pull test is negative. It is done by counting the number of hairs lost. The hair from the first morning combing or during washing should be counted. The hair is collected in a clear plastic bag for 14 days. The strands are recorded. If the hair count is >100/day, it is considered abnormal except after shampooing, where hair counts will be up to 250 and be normal.
Trichoscopy is a noninvasive method of examining hair and scalp. The test may be performed with the use of a handheld dermoscope or a video dermoscope. It allows differential diagnosis of hair loss in most cases.
There are two types of identification tests for female pattern baldness: the Ludwig Scale and the Savin Scale. Both track the progress of diffused thinning, which typically begins on the crown of the head behind the hairline, and becomes gradually more pronounced. For male pattern baldness, the Hamilton-Norwood scale tracks the progress of a receding hairline and/or a thinning crown, through to a horseshoe-shaped ring of hair around the head and on to total baldness.

In almost all cases of thinning, and especially in cases of severe hair loss, it is recommended to seek advice from a doctor or dermatologist. Many types of thinning have an underlying genetic or health-related cause, which a qualified professional will be able to diagnose.

SIGNS AND SYMPTOMS

Symptoms of alopecia include hair loss in patches usually in circular patterns, dandruff, skin lesions, and scarring. Alopecia areata (mild – medium level) usually shows in unusual hair loss areas e.g. eyebrows, backside of the head or above the ears where usually the male pattern baldness does not effect. In male-pattern hair loss, loss and thinning begin at the temples and the crown and either thins out or falls out. Female-pattern hair loss occurs at the frontal and parietal.

Excessive daily hair loss

People have between 100,000 and 150,000 hairs on their head. The number of strands normally lost in a day varies, but on average is 100. Seborrheic dermatitis, a condition in which an excessive amount of sebum is produced and builds up on the scalp (looking like an adult cradle cap) is also a symptom of hormonal imbalances, as is an excessively oily or dry scalp. Both can cause hair thinning.

Psychological

Hair thinning and baldness cause psychological stress due to its effect on appearance. Although societal interest in appearance has a long history, this particular branch of psychology came into its own during the 1960s and has gained momentum as messages associating physical attractiveness with success and happiness grow more prevalent.

The psychology of hair thinning is a complex issue. Hair is considered an essential part of overall identity: especially for women, for whom it often represents femininity and attractiveness. Men typically associate a full head of hair with youth and vigor. Although they may be aware of pattern baldness in their family, many are uncomfortable talking about the issue. Hair thinning is therefore a sensitive issue for both sexes. For sufferers, it can represent a loss of control and feelings of isolation. People experiencing hair thinning often find themselves in a situation where their physical appearance is at odds with their own self-image and commonly worry that they appear older than they are or less attractive to others. Psychological problems due to baldness, if present, are typically most severe at the onset of symptoms.

Hair loss induced by cancer chemotherapy has been reported to cause changes in self-concept and body image. Body image does not return to the previous state after regrowth of hair for a majority of patients. In such cases, patients have difficulties expressing their feelings (alexithymia) and may be more prone to avoiding family conflicts. Family therapy can help families to cope with these psychological problems if they arise.

PATHOPHYSIOLOGY

Hair follicle growth occurs in cycles. Each cycle consists of a long growing phase (anagen), a short transitional phase (catagen) and a short resting phase (telogen). At the end of the resting phase, the hair falls out (exogen) and a new hair starts growing in the follicle beginning the cycle again.

Normally, about 40 (0-78 in men) hairs reach the end of their resting phase each day and fall out. When more than 100 hairs fall out per day, clinical hair loss (telogen effluvium) may occur. A disruption of the growing phase causes abnormal loss of anagen hairs (anagen effluvium).

MANAGEMENT

Medications

Treatments for the various forms of hair loss have limited success. Three medications have evidence to support their use in male pattern hair loss: finasteride, dutasteride and minoxidil. They typically work better to prevent further hair loss than to regrow lost hair.

Minoxidil (Rogaine) is a nonprescription medication approved for male pattern baldness and alopecia areata. In a liquid or foam, it is rubbed into the scalp twice a day. However, only 30-40% of patients experience hair growth. Minoxidil is not effective for other causes of hair loss. Hair regrowth can take eight to 12 months. Treatment is continued indefinitely because, if the treatment is stopped, hair loss resumes again. Most frequent side effects are mild scalp irritation, allergic contact dermatitis, and increased facial hair.
SUMMARY

Hair loss or baldness (technically known as alopecia) is a loss of hair from the head or body. Baldness can refer to general hair loss or androgenic alopecia (male pattern baldness). Some types of baldness can be caused by alopecia areata, an autoimmune disorder. The extreme forms of alopecia areata are alopecia totalis, which involves the loss of all head hair, and alopecia universalis, which involves the loss of all hair from the head and the body.

Baldness and hypotrichosis can have many causes, including fungal infection (tinea capitis), traumatic damage, such as by compulsive pulling (trichotillomania), as a result of radiotherapy or chemotherapy, and as a result of nutritional deficiencies such as iron, and as a result of autoimmune phenomena, including alopecia areata and hair loss associated with systemic lupus erythematosus.

CAUSES

Although not completely understood, alopecia can have many causes:

Male pattern hair loss

More than 95% of hair thinning in men is male pattern hair loss (also known as male pattern baldness). Male pattern hair loss is characterized by hair receding from the lateral sides of the forehead (known as a “receding hairline”) and/or a thinning crown (balding to the area known as the ‘vertex’). Both become more pronounced until they eventually meet, leaving a horseshoe-shaped ring of hair around the back of the head.

The incidence of pattern baldness varies from population to population and is based on genetic background. Environmental factors do not seem to affect this type of baldness greatly. One large scale study in Maryborough, Victoria, Australia showed the prevalence of mid-frontal baldness increases with age and affects 73.5 percent of men and 57 percent of women aged 80 and over. A rough rule of thumb is that the incidence of baldness in males corresponds to chronological age. For example, according to Medem Medical Library’s website, male pattern baldness (MPB) affects roughly 40& million men in the United States. Approximately 25 percent of men begin balding by age 30; two-thirds begin balding by age 60.

There is a 4 in 7 chance of receiving the baldness gene. Onset of hair loss sometimes begins as early as the end of puberty, and is mostly genetically determined. It was previously believed that baldness was inherited from the maternal grandfather. While there is some basis for this belief, both parents contribute to their offspring’s likelihood of hair loss. Most likely, inheritance involves many genes with variable penetrance.

The trigger for this type of baldness is dihydrotestosterone, a more-potent form of testosterone often referred to by its acronym DHT. DHT is an androgenic hormone, body- and facial-hair growth promoter that can adversely affect the prostate as well as the hair located on the head. The mechanism by which DHT accomplishes this is not yet fully understood. In genetically prone scalps (i.e., those experiencing male or female pattern baldness), DHT initiates a process of follicular miniaturization, in which the hair follicle begins to deteriorate. As a consequence, the hair’s growth phase (anagen) is shortened, and young, unpigmented vellus hair is prevented from growing and maturing into the deeply rooted and pigmented terminal hair that makes up 90 percent of the hair on the head. In time, hair becomes thinner, and its overall volume is reduced so that it resembles fragile vellus hair or “peach fuzz” until, finally, the follicle goes dormant and ceases producing hair completely.

Nutrition

Studies have shown that poor nutrition, limited food intake, and deficiencies in certain nutrients can cause thinning. These include deficiencies of biotin, protein, zinc and poor human iron metabolism, although complete baldness is not usually seen. A diet high in animal fats (often found in fast food) and vitamin A is also thought to lead to hair loss.

Hypervitaminosis A
Iron deficiency or malnutrition in general
Infection

Dissecting cellulitis
Fungal infections (such as tinea capitis)
Tinea capitis
Folliculitis
Secondary syphilis
Demodex folliculorum, a microscopic mite that feeds on the sebum produced by the sebaceous glands, denies hair essential nutrients and can cause thinning. Demodex folliculorum is not present on every scalp and is more likely to live in an excessively oily scalp environment.
Drugs

Temporary or permanent hair loss can be caused by several medications, including those for blood pressure problems, diabetes, heart disease and cholesterol. Any that affect the body’s hormone balance can have a pronounced effect: these include the contraceptive pill, hormone replacement therapy, steroids and acne medications.
Medications (side effects from drugs, including chemotherapy, anabolic steroids, and birth control pills in which a large number of hairs enter the resting phase at the same time, causing shedding and subsequent thinning. The condition also presents as a side effect of chemotherapy – while targeting dividing cancer cells, this treatment also affects hair’s growth phase with the result that almost 90% of hairs fall out soon after chemotherapy starts.
Radiation to the scalp, as when radiotherapy is applied to the head for the treatment of certain cancers there, can cause baldness of the irradiated areas.
Pregnancy

Hair loss often follows childbirth without causing baldness. In this situation, the hair is actually thicker during pregnancy due to increased circulating oestrogens. After the baby is born, the oestrogen levels fall back to normal prepregnancy levels, and the additional hair foliage drops out. A similar situation occurs in women taking the fertility-stimulating drug clomiphene.

Other

Air and water pollutants as well as minerals in water and the phototoxic effects of sunlight can cause thinning by aging the scalp skin and damaging hair.
Alopecia areata is an autoimmune disorder also known as “spot baldness” that can result in hair loss ranging from just one location (Alopecia areata monolocularis) to every hair on the entire body (Alopecia areata universalis). Although thought to be caused by hair follicles becoming dormant, what triggers alopecia areata is not known. In most cases the condition corrects itself, but it can also spread to the entire scalp (alopecia totalis) or to the entire body (alopecia universalis).
Localized or diffuse hair loss may also occur in cicatricial alopecia (lupus erythematosus, lichen plano pilaris, folliculitis decalvans, central centrifugal cicatricial alopecia, postmenopausal frontal fibrosing alopecia, etc.). Tumours and skin outgrowths also induce localized baldness (sebaceous nevus, basal cell carcinoma, squamous cell carcinoma).
Hypothyroidism (an under-active thyroid) and the side effects of its related medications can cause hair loss, typically frontal, which is particularly associated with thinning of the outer third of the eyebrows (also seen with syphilis). Hyperthyroidism (an over-active thyroid) can also cause hair loss, which is parietal rather than frontal.
Temporary loss of hair can occur in areas where sebaceous cysts are present for considerable duration (normally one to several weeks).
Congenital triangular alopecia – It is a triangular, or oval in some cases, shaped patch of hair loss in the temple area of the scalp that occurs mostly in young children. The affected area mainly contains vellus hair follicles or no hair follicles at all, but it does not expand. Its causes are unknown, and although it is a permanent condition, it does not have any other effect on the affected individuals.
Gradual thinning of hair with age is a natural condition known as involutional alopecia. This is caused by an increasing number of hair follicles switching from the growth, or anagen, phase into a resting phase, or telogen phase, so that remaining hairs become shorter and fewer in number.
An unhealthy scalp environment can play a significant role in hair thinning by contributing to miniaturization or causing damage. Air and water pollutants, environmental toxins, conventional styling products and excessive amounts of sebum have the potential to build up on the scalp. This debris can block hair follicles and cause their deterioration and consequent miniaturization of hair. It can also physically restrict hair growth or damage the hair cuticle, leading to hair that is weakened and easily broken off before its natural lifecycle has ended.
Causes of alopecia include:

Alopecia mucinosa
Biotinidase deficiency
Chronic inflammation
Diabetes
Hair treatments (chemicals in relaxers, hair straighteners)
Lupus erythematosus
Pseudopelade of Brocq
Telogen effluvium
Tufted folliculitis
DIAGNOSIS

Because they are not usually associated with an increased loss rate, male-pattern and female-pattern hair loss do not generally require testing. If hair loss occurs in a young man with no family history, drug use could be the cause.

The pull test helps to evaluate diffuse scalp hair loss. Gentle traction is exerted on a group of hairs (about 40-60) on three different areas of the scalp. The number of extracted hairs is counted and examined under a microscope. Normally, fewer than three hairs per area should come out with each pull. If more than ten hairs are obtained, the pull test is considered positive.
The pluck test is conducted by pulling hair out “by the roots”. The root of the plucked hair is examined under a microscope to determine the phase of growth, and is used to diagnose a defect of telogen, anagen, or systemic disease. Telogen hairs have tiny bulbs without sheaths at their roots. Telogen effluvium shows an increased percentage of hairs upon examination. Anagen hairs have sheaths attached to their roots. Anagen effluvium shows a decrease in telogen-phase hairs and an increased number of broken hairs.
Scalp biopsy is used when the diagnosis is unsure; a biopsy allows for differing between scarring and nonscarring forms. Hair samples are taken from areas of inflammation, usually around the border of the bald patch.
Daily hair counts are normally done when the pull test is negative. It is done by counting the number of hairs lost. The hair from the first morning combing or during washing should be counted. The hair is collected in a clear plastic bag for 14 days. The strands are recorded. If the hair count is >100/day, it is considered abnormal except after shampooing, where hair counts will be up to 250 and be normal.
Trichoscopy is a noninvasive method of examining hair and scalp. The test may be performed with the use of a handheld dermoscope or a video dermoscope. It allows differential diagnosis of hair loss in most cases.
There are two types of identification tests for female pattern baldness: the Ludwig Scale and the Savin Scale. Both track the progress of diffused thinning, which typically begins on the crown of the head behind the hairline, and becomes gradually more pronounced. For male pattern baldness, the Hamilton-Norwood scale tracks the progress of a receding hairline and/or a thinning crown, through to a horseshoe-shaped ring of hair around the head and on to total baldness.

In almost all cases of thinning, and especially in cases of severe hair loss, it is recommended to seek advice from a doctor or dermatologist. Many types of thinning have an underlying genetic or health-related cause, which a qualified professional will be able to diagnose.

SIGNS AND SYMPTOMS

Symptoms of alopecia include hair loss in patches usually in circular patterns, dandruff, skin lesions, and scarring. Alopecia areata (mild – medium level) usually shows in unusual hair loss areas e.g. eyebrows, backside of the head or above the ears where usually the male pattern baldness does not effect. In male-pattern hair loss, loss and thinning begin at the temples and the crown and either thins out or falls out. Female-pattern hair loss occurs at the frontal and parietal.

Excessive daily hair loss

People have between 100,000 and 150,000 hairs on their head. The number of strands normally lost in a day varies, but on average is 100. Seborrheic dermatitis, a condition in which an excessive amount of sebum is produced and builds up on the scalp (looking like an adult cradle cap) is also a symptom of hormonal imbalances, as is an excessively oily or dry scalp. Both can cause hair thinning.

Psychological

Hair thinning and baldness cause psychological stress due to its effect on appearance. Although societal interest in appearance has a long history, this particular branch of psychology came into its own during the 1960s and has gained momentum as messages associating physical attractiveness with success and happiness grow more prevalent.

The psychology of hair thinning is a complex issue. Hair is considered an essential part of overall identity: especially for women, for whom it often represents femininity and attractiveness. Men typically associate a full head of hair with youth and vigor. Although they may be aware of pattern baldness in their family, many are uncomfortable talking about the issue. Hair thinning is therefore a sensitive issue for both sexes. For sufferers, it can represent a loss of control and feelings of isolation. People experiencing hair thinning often find themselves in a situation where their physical appearance is at odds with their own self-image and commonly worry that they appear older than they are or less attractive to others. Psychological problems due to baldness, if present, are typically most severe at the onset of symptoms.

Hair loss induced by cancer chemotherapy has been reported to cause changes in self-concept and body image. Body image does not return to the previous state after regrowth of hair for a majority of patients. In such cases, patients have difficulties expressing their feelings (alexithymia) and may be more prone to avoiding family conflicts. Family therapy can help families to cope with these psychological problems if they arise.

PATHOPHYSIOLOGY

Hair follicle growth occurs in cycles. Each cycle consists of a long growing phase (anagen), a short transitional phase (catagen) and a short resting phase (telogen). At the end of the resting phase, the hair falls out (exogen) and a new hair starts growing in the follicle beginning the cycle again.

Normally, about 40 (0-78 in men) hairs reach the end of their resting phase each day and fall out. When more than 100 hairs fall out per day, clinical hair loss (telogen effluvium) may occur. A disruption of the growing phase causes abnormal loss of anagen hairs (anagen effluvium).

MANAGEMENT

Medications

Treatments for the various forms of hair loss have limited success. Three medications have evidence to support their use in male pattern hair loss: finasteride, dutasteride and minoxidil. They typically work better to prevent further hair loss than to regrow lost hair.

Minoxidil (Rogaine) is a nonprescription medication approved for male pattern baldness and alopecia areata. In a liquid or foam, it is rubbed into the scalp twice a day. However, only 30-40% of patients experience hair growth. Minoxidil is not effective for other causes of hair loss. Hair regrowth can take eight to 12 months. Treatment is continued indefinitely because, if the treatment is stopped, hair loss resumes again. Most frequent side effects are mild scalp irritation, allergic contact dermatitis, and increased facial hair.
Finasteride (Propecia) is used in male-pattern hair loss in a pill form taken on a daily basis. It is not indicated for women and is not recommended in pregnant women. Treatment is effective within six to eight months of treatment. Side effects include decreased sex drive, erectile dysfunction, ejaculatory dysfunction, gynecomastia, and myopathy. Treatment should be continued as long as positive results occur. Once treatment is stopped, hair loss resumes again.
Corticosteroids injections of into the scalp can be used to treat alopecia areata. This type of treatment is repeated on a monthly basis. Oral pills for extensive hair loss may be used for alopecia areata. Results may take up to a month to be seen.
Immunosuppressants applied to the scalp have been shown to temporarily reverse alopecia areata, though the side effects of some of these drugs make such therapy questionable.
Anthralin maybe used in alopecia areata.
Hormonal modulators (oral contraceptives or antiandrogens such as spironolactone and flutamide) can be used for female-pattern hair loss associated with hyperandrogenemia.
Surgery

Hair Transplantation is usually carried out under local anaesthetic. A surgeon will move healthy hair from the back and sides of the head to areas of thinning. The procedure can take between four and eight hours, and additional sessions can be carried out to make hair even thicker. Transplanted hair falls out within a few weeks, but regrows permanently within months. **Hair transplants, takes tiny plugs of skin, each which contains a few hairs, and implants the plugs into bald sections. The plugs are generally taken from the back or sides of the scalp. Several transplant sessions may be necessary. Egg oil, in Indian, Japanese, Unani (Roghan Baiza Murgh) and Chinese traditional medicine, was traditionally used as a treatment for hairloss.

ETYMOLOGY

The term alopecia is formed from the Greek alópex (αλώπηξ), meaning fox. The origin of this usage is because this animal sheds its coat twice a year, or because in ancient Greece foxes often lost hair because of mange.

The term bald likely derives from the English word balde, which means “white, pale”, or Celtic ball, which means “white patch or blaze”, such as on a horse’s head.

TERMINOLOGY

Baldness is the partial or complete lack of hair growth, and part of the wider topic of “hair thinning”. The degree and pattern of baldness varies, but its most common cause is androgenic alopecia, alopecia androgenetica, or alopecia seborrheica, with the last term primarily used in Europe.