Oral manifestation of the dermatoses with autoimmune components.

 

Oral lichen planus

Oral lichen planus (LIE-kun PLAY-nus) is an inflammatory condition that affects mucous membranes inside the mouth. Oral lichen planus may appear as white, lacy patches; red, swollen tissues; or open sores. These lesions may cause burning, pain or other discomfort.

Oral lichen planus can’t be passed from one person to another. The disorder occurs when the immune system mounts an attack against cells of the oral mucous membranes. The reason for this abnormal immune response is unknown.

Oral lichen planus is usually an ongoing (chronic) condition. Treatments that suppress the immune system abnormalities may improve more severe lesions and lessen pain.

People with oral lichen planus may also have related lichen planus lesions on the skin, genitals or other parts of the body.

Causes

The cause of oral lichen planus is unknown. The lesions that appear are the result of inflammation controlled by specific white blood cells called T lymphocytes. Normally, these cells are active at the site of disease or injury.

However, certain diseases, medical conditions or other factors may act as triggers of the inflammatory disorder in some people.

Factors that may act as triggers of oral lichen planus:

• Hepatitis C infection and other types of liver disease

• Hepatitis B vaccine

• Certain types of flu vaccines

• Allergy-causing agents (allergens), such as foods, dental materials or other substances

• Nonsteroidal anti-inflammatory drugs, such as ibuprofen  and naproxen

• Certain medications for heart disease, high blood pressure or arthritis

Factors that may complicate the condition or worsen symptoms include:

• Tobacco products

• Alcohol

• Rough dental work

• Poorly fitting dentures

• Poor oral habits, such as biting the lip or cheeks

• Buildup of dental plaque or tartar

• Stress

Anyone can develop oral lichen planus, but the condition most often affects middle-aged women.

Symptoms

The primary signs and symptoms of oral lichen planus are the lesions affecting the mucous membranes of the mouth.

Appearance
The lesions may appear as:

• Lacy, white, raised patches of tissues

• Red, swollen, tender patches of tissues

• Open sores

Location
These lesions may appear on the following sites:

• Inside of the cheeks, the most common location

• Gums

• Tongue

• Inner tissues of the lips

• Throat

• Esophagus

 

Pain or discomfort
The red, inflamed lesions and open sores of oral lichen planus can cause a burning sensation or pain. The white, lacy patches alone usually don’t cause discomfort, except when they appear on the tongue.

Other signs or symptoms
Other signs or symptoms may include:

• A metallic taste or a blunted taste sensation if the tongue is affected

• Dry mouth

• Difficulty swallowing if the throat or esophagus is affected

• Sensitivity to hot or spicy foods

• Bleeding and irritation with tooth brushing

Other types of lichen planus

• Skin. Lesions usually appear as purplish, flat-topped bumps that are often itchy.

• Genitals. Lesions on external genitalia resemble those affecting the skin. Lesions affecting the mucous membrane of the vagina resemble those affecting the mouth.

• Scalp. When skin lesions appear on the scalp — a rare condition — they may cause temporary or permanent hair loss.

• Nails. Lichen planus of the toenails or fingernails, also rare, may result in ridges on the nails, thinning or splitting of nails, and temporary or permanent nail loss.

Additional tests:

Biopsy (The tissue is examined under a microscope to identify a typical pattern of T lymphocytes consistent with a diagnosis of oral lichen planus. Other more specialized microscopic tests may be needed to identify profiles of immune system proteins commonly associated with the disorder.)

Hepatitis C test (Hepatitis C is a possible trigger for oral lichen planus).

Allergy tests.

Treatments and drugs

Oral lichen planus is a chronic condition that can be difficult to manage. The treatment goals are to help severe lesions heal and to lessen pain or other discomfort.

Corticosteroids
Corticosteroids may reduce inflammation associated with oral lichen planus. The side effects vary depending on whether it’s used as a mouthwash or ointment applied directly to the mucous membrane (topical), taken as a pill (oral), or administered as an injection. The potential benefit of corticosteroids needs to be balanced with possible side effects, which include the following:

• Topical. Topical corticosteroids to treat oral lichen planus may result in oral thrush, an infection caused by the Candida albicans fungus. If this infection occurs, you’ll need to take an antifungal medication. Long-term use of topical corticosteroids may also cause suppression of adrenal gland function and a lessening of the treatment effect.

• Oral. Long-term use of oral corticosteroids can cause weakening of the bones (osteoporosis), diabetes, high blood pressure, high cholesterol and other serious side effects.

• Injections. Injections may be administered directly into lesions. Repeated use of corticosteroid injections can cause some of the same side effects as oral corticosteroids.

Retinoids
Retinoids are synthetic versions of vitamin A that can be applied as a topical ointment or taken orally. The topical treatment doesn’t cause the same side effects associated with corticosteroids, but it may irritate the mucous membranes of the mouth.

Because both topical and oral retinoids can cause birth defects, the drug shouldn’t be used by women who are pregnant or planning to become pregnant in the near future.

Nonsteroidal ointments
In the past few years, several reports have shown the effectiveness of topical medications, called calcineurin inhibitors, which are closely related to or identical to oral medications used to prevent rejection of transplanted organs. These treatments appear to be effective for the treatment of oral lichen planus. Examples of these topical medications include tacrolimus (Protopic ointment) and pimecrolimus (Elidel cream).

Addressing triggers

• Drugs. You may ask the patient  to stop taking a drug or to try an alternative drug to the one that may be acting as a trigger. This action may require consultation with the doctor who originally prescribed this medication.

• Allergen. If tests suggest that an allergen may be a potential trigger, you have to find this allergen and to remove it. It can be, also, some dental device. You may need dermatologist or an allergist consultation for additional treatment.

• Stress. Because stress may be a factor that complicates symptoms or triggers the recurrence of symptoms,patient  may need to develop skills to avoid or manage stress. You may refer the patient to a psychotherapist, psychiatrist or other specialist in mental health care who can help to identify stressors, develop stress management strategies or address other mental health care concerns.

 

Systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a long-term autoimmune disorder that may affect the skin, joints, kidneys, brain, and other organs.

SLE is one of several diseases known as “the great imitators“ because it often mimics or is mistaken for other illnesses

Causes

Systemic lupus erythematosus (SLE) is an autoimmune disease, which means the body’s immune system mistakenly attacks healthy tissue. This leads to long-term (chronic) inflammation.

The underlying cause of autoimmune diseases is not fully known.

SLE is much more common in women than men. It may occur at any age, but appears most often in people between the ages of 10 and 50. African Americans and Asians are affected more often than people from other races. SLE may also be caused by certain drugs.

Symptoms

Symptoms vary from person to person, and may come and go. Almost everyone with SLE has joint pain and swelling. Some develop arthritis. Frequently affected joints are the fingers, hands, wrists, and knees.

Other common symptoms include:

• Chest pain when taking a deep breath

• Fatigue

• Fever with no other cause

• General discomfort, uneasiness, or ill feeling (malaise)

• Hair loss

• Mouth sores

• Sensitivity to sunlight

• Skin rash — a “butterfly” rash over the cheeks and bridge of the nose affects about half of people with SLE. The rash gets worse in sunlight. The rash may also be widespread.

• Swollen lymph nodes

Other symptoms depend on what part of the body is affected:

• Brain and nervous system: headaches, numbness, tingling, seizures, vision problems, personality changes

• Digestive tract: abdominal pain, nausea, and vomiting

• Heart: abnormal heart rhythms (arrhythmias)

• Lung: coughing up blood and difficulty breathing

• Skin: patchy skin color, fingers that change color when cold (Raynaud’s phenomenon)

Some patients only have skin symptoms. This is called discoid lupus.

 

Dermatological manifestations

As many as 30% of sufferers have some dermatological symptoms (and 65% suffer such symptoms at some point), with 30% to 50% suffering from the classic malar rash (or butterfly rash) associated with the disease. Some may exhibit thick, red scaly patches on the skin (referred to as discoid lupus). Alopecia; mouth, nasal, urinary tract and vaginal ulcers, and lesions on the skin are also possible manifestations. Tiny tears in delicate tissue around the eyes can occur after even minimal rubbing.

Musculoskeletal

The most commonly sought medical attention is for joint pain, with the small joints of the hand and wrist usually affected, although all joints are at risk. The Lupus Foundation of America estimates more than 90 percent of those affected will experience joint and/or muscle pain at some time during the course of their illness.Unlike rheumatoid arthritis, lupus arthritis is less disabling and usually does not cause severe destruction of the joints. Fewer than ten percent of people with lupus arthritis will develop deformities of the hands and feet. SLE patients are at particular risk of developing osteoarticular tuberculosis.

A possible association between rheumatoid arthritis and SLE has been suggested, and SLE may be associated with an increased risk of bone fractures in relatively young women.

Hematological

Anemia may develop in up to 50% of cases. Low platelet and white blood cell counts may be due to the disease or a side effect of pharmacological treatment. People with SLE may have an association withantiphospholipid antibody syndrome (a thrombotic disorder), wherein autoantibodies to phospholipids are present in their serum. Abnormalities associated with antiphospholipid antibody syndrome include a paradoxical prolonged partial thromboplastin time (which usually occurs in hemorrhagic disorders) and a positive test for antiphospholipid antibodies; the combination of such findings have earned the term “lupus anticoagulant-positive”. Another autoantibody finding in SLE is the anticardiolipin antibody, which can cause a false positive test for syphilis.

Cardiac

A person with SLE may have inflammation of various parts of the heart, such as pericarditis, myocarditis, and endocarditis. The endocarditis of SLE is characteristically noninfective (Libman-Sacks endocarditis), and involves either the mitral valve or the tricuspid valve. Atherosclerosis also tends to occur more often and advances more rapidly than in the general population.

Pulmonary

Lung and pleura inflammation can cause pleuritis, pleural effusion, lupus pneumonitis, chronic diffuse interstitial lung disease, pulmonary hypertension, pulmonary emboli, pulmonary hemorrhage, and shrinking lung syndrome.

Renal

Painless hematuria or proteinuria may often be the only presenting renal symptom. Acute or chronic renal impairment may develop with lupus nephritis, leading to acute or end-stage renal failure. Because of early recognition and management of SLE, end-stage renal failure occurs in less than 5% of cases.

A histological hallmark of SLE is membranous glomerulonephritis with “wire loop” abnormalities. This finding is due to immune complex deposition along the glomerular basement membrane, leading to a typical granular appearance in immunofluorescence testing.

Neuropsychiatric

Neuropsychiatric syndromes can result when SLE affects the central or peripheral nervous systems. The American College of Rheumatology defines 19 neuropsychiatric syndromes in systemic lupus erythematosus. The diagnosis of neuropsychiatric syndromes concurrent with SLE is one of the most difficult challenges in medicine, because it can involve so many different patterns of symptoms, some of which may be mistaken for signs of infectious disease or stroke.

The most commoeuropsychiatric disorder people with SLE have is headache,although the existence of a specific lupus headache and the optimal approach to headache in SLE cases remains controversial. Other commoeuropsychiatric manifestation of SLE include cognitive dysfunction, mood disorder, cerebrovascular disease, seizures, polyneuropathy, anxiety disorder, and psychosis. It can rarely present with intracranial hypertension syndrome, characterized by an elevated intracranial pressure, papilledema, and headache with occasional abducens nerve paresis, absence of a space-occupying lesion or ventricular enlargement, and normalcerebrospinal fluid chemical and hematological constituents.

More rare manifestations are acute confusional state, Guillain-Barré syndrome, aseptic meningitis, autonomic disorder, demyelinating syndrome, mononeuropathy (which might manifest as mononeuritis multiplex), movement disorder (more specifically, chorea), myasthenia gravis, myelopathy, cranial neuropathy and plexopathy.

Neurological

Neural symptoms contribute to a significant percentage of morbidity and mortality in patients with lupus. As a result, the neural side of lupus is being studied in hopes of reducing morbidity and mortality rates. The neural manifestation of lupus is known as neuropsychiatric systematic lupus erythematosus (NPSLE). One aspect of this disease is severe damage to the epithelial cells of the blood–brain barrier.

Lupus has a wide range of symptoms which span the body. The neurological symptoms include headaches, depression, seizures, cognitive dysfunction, mood disorder, cerebrovascular disease,  polyneuropathy, anxiety disorder, psychosis, and in some extreme cases, personality disorders. In certain regions, depression reportedly affects up to 60% of women suffering from SLE.

Reproductive

Further information: Systemic lupus erythematosus and pregnancy

SLE causes an increased rate of fetal death in utero and spontaneous abortion (miscarriage). The overall live-birth rate in SLE patients has been estimated to be 72%. Pregnancy outcome appears to be worse in SLE patients whose disease flares up during pregnancy.

Neonatal lupus is the occurrence of SLE symptoms in an infant born from a mother with SLE, most commonly presenting with a rash resembling discoid lupus erythematosus, and sometimes with systemic abnormalities such as heart block or hepatosplenomegaly.Neonatal lupus is usually benign and self-limited.

Systemic

Fatigue in SLE is probably multifactorial and has been related to not only disease activity or complications such as anemia or hypothyroidism, but also to pain, depression, poor sleep quality, poor physical fitness and perceived lack of social support.

Genetics

The first mechanism may arise genetically. Research indicates SLE may have a genetic link. SLE does run in families, but no single causal gene has been identified. Instead, multiple genes appear to influence a person’s chance of developing lupus when triggered by environmental factors. The most important genes are located in the HLA region on chromosome 6, where mutations may occur randomly (de novo) or may be inherited. HLA class I, class II, and class III are associated with SLE, but only classes I and II contribute independently to increased risk of SLE. Other genes which contain risk variants for SLE are IRF5, PTPN22, STAT4, CDKN1A, ITGAM, BLK, TNFSF4 and BANK1. Some of the susceptibility genes may be population specific.

Pathophysiology

One manifestation of SLE is abnormalities in apoptosis, a type of programmed cell death in which aging or damaged cells are neatly disposed of as a part of normal growth or functioning.

Laboratory tests

Antinuclear antibody (ANA) testing and anti-extractable nuclear antigen (anti-ENA) form the mainstay of serologic testing for SLE. Several techniques are used to detect ANAs. Clinically the most widely used method is indirect immunofluorescence. The pattern of fluorescence suggests the type of antibody present in the patient’s serum.

ANA screening yields positive results in many connective tissue disorders and other autoimmune diseases, and may occur iormal individuals. Subtypes of antinuclear antibodies include anti-Smith and anti-double strandedDNA (dsDNA) antibodies (which are linked to SLE) and anti-histone antibodies (which are linked to drug-induced lupus). Anti-dsDNA antibodies are highly specific for SLE; they are present in 70% of cases, whereas they appear in only 0.5% of people without SLE. The anti-dsDNA antibody titers also tend to reflect disease activity, although not in all cases.Other ANA that may occur in SLE sufferers are anti-U1 RNP (which also appears in systemic sclerosis), SS-A (or anti-Ro) and SS-B (or anti-La; both of which are more common in Sjögren’s syndrome). SS-A and SS-B confer a specific risk for heart conduction block ieonatal lupus.

Other tests routinely performed in suspected SLE are complement system levels (low levels suggest consumption by the immune system), electrolytes and renal function (disturbed if the kidney is involved), liver enzymes, and complete blood count.

The lupus erythematosus (LE) cell test was commonly used for diagnosis, but it is no longer used because the LE cells are only found in 50–75% of SLE cases, and they are also found in some people with rheumatoid arthritis, scleroderma, and drug sensitivities. Because of this, the LE cell test is now performed only rarely and is mostly of historical significance.

Criteria for individual diagnosis

Recursive partitioning has been used to identify more parsimonious criteria.This analysis presented two diagnostic classification trees:

1.     Simplest classification tree: SLE is diagnosed if a person has an immunologic disorder (anti-DNA antibody, anti-Smith antibody, false positive syphilis test, or LE cells) or malar rash. It has sensitivity = 92% and specificity = 92%.

2.     Full classification tree: Uses 6 criteria. It has sensitivity = 97% and specificity = 95%.

Treatment

The treatment of SLE involves preventing flares and reducing their severity and duration when they occur.

Treatment can include corticosteroids and anti-malarial drugs. Certain types of lupus nephritis such as diffuse proliferative glomerulonephritis require bouts of cytotoxic drugs. These drugs include cyclophosphamide and mycophenolate.

Hydroxychloroquine (HCQ) was approved by the FDA for lupus in 1955. Some drugs approved for other diseases are used for SLE ‘off-label’. In November 2010, an FDA advisory panel recommended approving Benlysta (belimumab) as a treatment for the pain and flare-ups common in lupus. The drug was approved by the FDA in March 2011.

Also, immunosuppressive drugs, disease-modifying antirheumatic, analgesics and  intravenous Immunoglobulins can be used.

 

 

Erythema multiforme

Erythema multiforme (EM) is an acute, self-limited, and sometimes recurring skin condition that is considered to be a type IV hypersensitivity reaction associated with certain infections, medications, and other various triggers.

Symptoms:

•         Fever

•         General ill feeling

•         Itching of the skin

•         Joint aches

•         Multiple skin lesions:

–       Start quickly and may return

–       May spread

–       May appear as a nodule, papule, or macule and may look like hives

–       Central sore surrounded by pale red rings, also called a “target”, “iris”, or “bulls-eye”

–       May have vesicles and blisters of various sizes (bullae)

–       Located on the upper body, legs, arms, palms, hands, or feet

–       May involve the face or lips

–       Usually even on both sides (symmetrical)

•         Bloodshot eyes

•         Dry eyes

•         Eye burning, itching, and discharge

•         Eye pain

•         Mouth sores

•         Vision problems

 

History:

•         In EM, there may be no prodrome or a mild upper respiratory tract infection.

•         The rash starts abruptly, usually within 3 days. It starts on the extremities, being symmetrical and spreading centrally.

•         Half of children with the rash have recent herpes labialis.

•         It usually precedes the erythema multiforme by 3 to 14 days but it can sometimes be present at the onset.

Examination:

•         The iris or target lesion is the classical feature of the disease.

•         Initially there is a dull red flat spot or wheal that enlarges slightly up to 2 cm over 24 to 48 hours.

•         In the middle, a small bump, vesicle, or bulla develops, flattens, and then may clear. The intermediate ring forms and becomes raised, pale, and swollen. The periphery slowly becomes purple and forms a concentric lesion, resembling a target. Some lesions are atypical targets with only 2 concentric rings.

•         The Koebner phenomenon may occur. This is where a lesion occurs along the line of trauma and it is typical of psoriasis and lichen planus.

•         Lesions appear first on the extensor surfaces of the periphery and extend centrally. The palms, neck and face are often involved but the soles and flexures of the extremities less often.

•         There may be mucosal involvement in 70% of patients but it tends to be mild and limited to just one mucosal surface (for example mouth or vulva).

•         Oral lesions are most common with lips, palate and gingiva affected. There may be red conjunctivae and tearing, but eye involvement tends to be mild.

•         Genital involvement can produce painful hemorrhagic bullae and erosions.

Investigations:
No specific investigations are indicated.

•         Nikolsky’s sign is negative

•         A punch biopsy may be required to confirm diagnosis.

Management:
In recurrent disease due to HSV, antiviral therapy is helpful.

•         Symptomatic treatment may include analgesics, mouth wash and local skin care.

•         Steroid creams may be used. If the mouth is very sore, attention may have to be given to hydration and nutrition.

•         Lubricating drops for eyes may be required.

 

Stevens–Johnson syndrome:

•         Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are two forms of a life-threatening skin condition, in which cell death causes the epidermis to separate from the dermis

•         The syndrome is thought to be a hypersensitivity complex that affects the skin and the mucous membranes. Although the majority of cases are idiopathic (without a known cause), the main class of known causes is medication, followed by infections and, rarely, cancers.

Symptoms

•         SJS usually begins with fever, sore throat, and fatigue, which is misdiagnosed and usually treated with antibiotics.

•         Ulcers and other lesions begin to appear in the mucous membranes, almost always in the mouth and lips but also in the genital and anal regions.

•         Those in the mouth are usually extremely painful and reduce the patient’s ability to eat or drink.

•          Conjunctivitis of the eyes occurs in about 30% of children who develop SJS.

•         A rash of round lesions about an inch across arises on the face, trunk, arms and legs, and soles of the feet, but usually not the scalp.

Stevens-Johnson syndrome – affection of the tongue

Lips lesions in SJS

Treatment:

•         SJS constitutes a dermatological emergency. All medications should be discontinued, particularly those known to cause SJS reactions. Patients with documented mycoplasma infections can be treated with oral macrolide or oral doxycycline.

•         Initially, treatment is similar to that for patients with thermal burns, and continued care can only be supportive (e.g. intravenous fluids and nasogastric or parenteral feeding) and symptomatic (e.g.,analgesic mouth rinse for mouth ulcer). 

•         Dermatologists and surgeons tend to disagree about whether the skin should be debrided.

•         Beyond this kind of supportive care, there is no accepted treatment for SJS. Treatment with corticosteroids is controversial.

•          Early retrospective studies suggested that corticosteroids increased hospital stays and complication rates. There are no randomized trials of corticosteroids for SJS, and it can be managed successfully without them.

•         Intravenous immunoglobulin (IVIG) treatment has shown some promise in reducing the length of the reaction and improving symptoms. Other common supportive measures include the use of topical pain anesthetics and antiseptics, maintaining a warm environment, and intravenous analgesics. An ophthalmologist should be consulted immediately, as SJS frequently causes the formation of scar tissue inside the eyelids, leading to corneal vascularization, impaired vision and a host of other ocular problems.

 

 

References:

1.      Danilevskiy M.F. et al. “ Diseases of the mucous membrane of the mouth.” – K.: “Medytsyna”, 2010.

2.      Bruch J.M. Clinical oral medicine and pathology/ J.M. Bruch, N.S. Treister// London.:Humana Press, 2010

3.      Cawson R. E. Cawson’s essentials of oral pathology and oral medicine. Seventh edition/ Cawson R. E. et. al. //Elsevier science limited, 2002.

4.      Slootweg P. Dental pathology – a practical introduction/ P.J. Slootweg// Berlin.: Springer, 2007.

5.      Da Silva J.D. Oxford American Handbook of Clinical Dentistry (Oxford American Handbooks in Medicine) / J.D. Da Silva et al.// Oxford University Press, 2007.

.

 

 

Information was prepared by Sukhovolets I.O.