Autoimmune diseases of skin

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As rheumatologists, we often work with our colleagues in dermatology to diagnose and treat autoimmune diseases. Rashes can be seen in many of the diseases we treat including scleroderma, vasculitis, lupus and dermatomyositis.

Lupus

Many physicians and patients are aware of the classic malar (over cheeks and nose) rash seen in systemic lupus erythematosus (SLE or lupus) that can be triggered by exposure to sunlight. Many other rashes, however, can be seen in lupus, including a diffuse circular rash known as subacute cutaneous lupus erythematosus (SCLE) and a scarring rash often seen on the scalp called discoid lupus (see images below).

The discoid rash may exist without lupus affecting other parts of the body such as the kidneys and joints. It is often treated by dermatologists with local steroid injections.This rash must be evaluated immediately because, unlike other lupus rashes, it can cause scarring.

Medications used for these lupus rashes include topical steroid creams and, if necessary, medicines that help control an overactive immune system that are taken by mouth such as hydroxychloroquine (Plaquenil), quinicrine, and mycophenolate mofetil (Cellcept).

Dermatomyositis

Dermatomyositis is a systemic autoimmune disease that often begins with arm and leg weakness as well as several different rashes including: a rash on the hands (Gottron’s), around the eyes (heliotrope), and/or across the back and chest (shawl rash; see images at right). Diagnosis can be established with a history and exam, a skin and/ or muscle biopsy and lab tests.

Dermatologists often help to establish this diagnosis and may do a skin biopsy to exclude other potential causes of these rashes including cancer, allergic reactions to medications, and urticaria (hives).

Treatment usually involves steroids taken by mouth and medicines to suppress the immune system such as methotrexate, azathioprine or mycophenolate mofetil (Cellcept).

At Arthritis and Rheumatism Associates, PC, we work closely with your dermatologist to manage any rash that may be part of an autoimmune disease.

What is causing my rash?

1. Bites and stings

Many insects can cause a rash through a bite or sting. Although the reaction will vary depending on the person and the animal, symptoms often include:

  • redness and rash
  • itching
  • pain
  • swelling – either localized to the site of the bite or sting or more widespread

2. Flea bites

Fleas are tiny jumping insects that can live in fabrics within the home. They have a very fast breeding cycle and can take over a home very rapidly.

  • flea bites on humans often appear as red spots
  • the skin can become irritated and painful
  • secondary infections can be caused by scratching

3. Fifth disease

Also known as erythema infectiosum and slapped cheek syndrome, fifth disease is caused by the parvovirus B19. One of the symptoms is a rash, which appears in three stages:

  • A blotchy red rash on the cheeks with groups of red papules.
  • After 4 days, a net of red marks may appear on the arms and trunk.
  • In the third stage, the rash only appears after exposure to sunlight or heat.

4. Impetigo

Impetigo is a highly contagious skin infection that most commonly affects children. The first sign is normally a patch of red, itchy skin. There are two types of impetigo:

  • Non-bullous impetigo – red sores appear around the mouth and nose.
  • Bullous impetigo – less common, generally affects children under 2. Medium to large blisters appear on the trunk, arms, and legs.

5. Shingles

Shingles is an infection of an individual nerve. It is caused by the same virus as chickenpox – the varicella-zoster virus. Symptoms include:

  • A rash similar to chickenpox in a band around the infected nerve.
  • Blisters can merge producing a solid red band.
  • Rash is often painful.

6. Scabies

Scabies is a skin condition caused by a microscopic mite. It is very contagious and spreads easily through person-to-person contact. Symptoms include:

  • Intense itching – often worse at night.
  • Rash – appears in lines as the mite burrows. Blisters are sometimes present.
  • Sores – may appear where the rash has been scratched.

7. Eczema

Eczema is one of the most common skin conditions. It often first develops in childhood. Symptoms depend on the type of eczema and on the age of the individual but they often include:

  • dry scaly patches on the skin
  • intensely itchy rash
  • cracked and rough skin

8. Hay fever

Hay fever, or allergic rhinitis, is an allergic response to pollen. Symptoms can be similar to those of a common cold, such as:

  • runny nose
  • watery eyes
  • sneezing

Hay fever can also cause a rash, similar to hives. These will appear as itchy red patches or eruptions on the skin.

9. Scarlet fever

Scarlet fever is a disease caused by a toxin released by a bacteria – Streptococcus pyogenes – the same bacteria that is responsible for Strep throat. Symptoms include a sore throat, rash, and fever. The rash has the following characteristics:

  • red blotches
  • blotches turn to fine pink-red rash like sunburn
  • skin feels rough

10. Rheumatic fever

Rheumatic fever is an inflammatory reaction to a streptococcal infection, such as Strep throat. It most commonly affects children aged 5-15. Symptoms include:

  • small painless bumps under skin
  • red skin rash
  • swollen tonsils

11. Mono (mononucleosis)

Mono, or mononucleosis, is caused by a virus. It is rarely serious, but symptoms can include:

  • a pink, measle-like rash
  • body aches
  • high fevers

12. Ringworm

Ringworm, despite its name, is caused by a fungus. The fungal infection affects the top layer of the skin, scalp, and nails. Symptoms vary depending on the site of the infection, but can include:

  • itchy, red rash in rings – sometimes slightly raised
  • small patches of scaly skin
  • hair near patches breaks away

13. Measles

Measles is a highly contagious disease caused by the rubeola virus. Symptoms include:

  • a reddish-brown rash
  • small grayish-white spots with bluish-white centers in the mouth
  • dry cough

14. Yeast infection (candidiasis)

Candidiasis is a common fungal infection of the genitals. It affects both sexes, but more commonly, women. Symptoms include:

  • rash
  • pain and soreness in the genital area
  • itching, burning, and irritation

15. Stasis dermatitis

Stasis dermatitis is also known as varicose eczema. It develops due to poor circulation and most commonly affects the lower legs. Symptoms include:

  • varicose veins covered in itchy, dry skin
  • red, swollen, painful skin, which may weep or crust over
  • heavy, aching legs after standing for some time

16. German measles

Also known as rubella, German measles are an infection caused by the rubella virus. Symptoms include:

  • rash – less bright than measles, often begins on the face
  • inflamed, red eyes
  • stuffy nose

17. Sepsis

Sepsis, often called blood poisoning, is a medical emergency. It is the result of a wide scale immune response to an infection. Symptoms vary, but can include:

  • a rash that does not fade under pressure
  • fever
  • increased heart rate

18. West Nile virus

West Nile virus is an infection spread by mosquitos. Often, there are no symptoms, but if they do occur, they can include:

  • raised and/or flat, pink skin rash on the trunk, arms, or legs
  • excessive sweating
  • vomiting

19. Lyme disease

Lyme disease is a bacterial infection transmitted to humans by the bite of an infected tick. The symptoms include an erythema migrans rash that often appears in the early stages of the disease.

  • The rash begins as a small red area that may be warm to the touch but not itchy.
  • The center loses color, giving it a bull’s-eye appearance.
  • The rash does not necessarily appear at the site of the tick bite.

20. Cellulitis

Cellulitis is a bacterial infection of the deep layer of skin – the dermis. It normally occurs when bacteria enter through a break in the skin. Symptoms include:

  • Skin sores or rash that starts suddenly and grows quickly.
  • Warm skin around the redness.
  • Fever and fatigue.

21. MRSA

MRSA (methicillin-resistant staphylococcus aureus) is a contagious bacterial infection that is resistant to a range of antibiotics. This makes it difficult to treat. Symptoms include:

  • rash
  • swelling and tenderness in the affected part of the body
  • wounds that do not heal

Photo credit: National Institute of Allergy and Infectious Diseases (NIAID)

22. Chickenpox

Chickenpox is an infection by the varicella zoster virus. It is unpleasant, but most people recover within a couple of weeks. Symptoms include:

  • An itchy rash of small red spots first appears on the face and trunk, and then spreads across the body.
  • Spots then develop blisters on top.
  • After 48 hours, the blisters cloud and start to dry out.

23. Lupus

Lupus is an autoimmune disease, meaning that the immune system attacks healthy tissue. Symptoms vary widely from person to person, but can include:

  • Butterfly-shaped rash across the cheeks and the bridge of the nose.
  • Flaky red spots or a purple, scaly rash on the face, neck, or arms.
  • Skin sensitivity to the sun.

24. Toxic shock syndrome

Toxic shock syndrome is a rare condition sparked by a bacterial infection. It develops quickly and can be life-threatening. All people who have toxic shock syndrome have fever and a rash with the following characteristics:

  • looks similar to sunburn and covers most of the body
  • flat not raised
  • turns white when pressed

25. Acute HIV infection

During the first stages of HIV, levels of the virus in the blood are very high because the immune system has not yet started tackling the infection. Early symptoms include a rash with the following features:

  • mostly affects the upper part of the body
  • flat or barely raised small red dots
  • not generally itchy

26. Hand, foot, and mouth

Hand, foot, and mouth is a childhood illness resulting from a viral infection. Symptoms include:

  • Rash – flat, non-itchy red blisters on the hands and soles of the feet.
  • Loss of appetite.
  • Ulcers on the throat, tongue, and mouth.

Image credit: KlatschmohnAcker

27. Acrodermatitis

Acrodermatitis, a type of pustular psoriasis, is also known as Gianotti-Crosti syndrome. It is associated with viral infections. Symptoms include:

  • itchy purple or red blisters
  • swollen lymph nodes
  • bloated abdomen

28. Hookworm

Hookworm is a common intestinal parasite. It can cause a range of complications. Symptoms include:

  • Skin rash in one particular area that is red, itchy, and raised.
  • Breathing complications.
  • Extreme tiredness.

29. Kawasaki disease

Kawasaki’s disease is a rare syndrome that affects children. It is characterized by an inflammation of the walls of the arteries throughout the body. Symptoms include:

  • A rash on the legs, arms, and torso and between the genitals and anus.
  • A rash on the soles of the feet and palms of the hand, sometimes with peeling skin.
  • Swollen, chapped, and dry lips.

30. Syphilis

Syphilis is a sexually transmitted bacterial infection. The disease is treatable, but will not go away on its own. Symptoms vary depending on the stage of the disease and include:

  • Initially – painless, firm, and round syphilitic sores (chancres).
  • Later – non-itchy red/brown rash that starts on the trunk and spreads across the body.
  • Oral, anal, and genital wart-like sores.

31. Typhoid

Typhoid is caused by a bacterial infection. It is spread quickly by contact with the feces of an infected person. If untreated, 25 percent of cases end in death. Symptoms can include:

  • Rash – rose-colored spots, especially on the neck and abdomen.
  • Fever – up to 104 degrees Fahrenheit.
  • Abdominal pain, diarrhea, and constipation.

Image credit: Charles N. Farmer, CDC/ Armed Forces Institute of Pathology, 1964

32. Dengue fever

Dengue fever, also called breakbone fever, is transmitted by mosquitos. The condition ranges from mild to severe. Symptoms can include:

  • Initially a flat, red rash appears over most of the body.
  • Later, a secondary rash appears, similar to measles.
  • Severe joint and muscle aches.

Image credit: calliopejen, 2009

33. Ebola

Ebola is a serious viral disease; it spreads rapidly through families and friends and can often be fatal. Often, a rash is one of the symptoms:

  • Initially, a short-lived mild rash may be present.
  • Rashes begin to peel and look like sunburn.
  • Later in the disease, the rash may turn to abscesses.

34. SARS

Severe acute respiratory syndrome (SARS) is a contagious and sometimes fatal respiratory illness. Symptoms can include:

  • skin rash
  • chills
  • stiff muscles

35. Contact dermatitis

Contact dermatitis occurs when the skin comes in contact with an irritant; it is relatively common, and can be unpleasant. Symptoms include:

  • red, flaky rash that stings
  • blistered skin
  • burning sensation
  • cracked skin

36. Fungal infection

Although some fungi live naturally on the human body, sometimes, they can overtake. Symptoms depend on where the infection strikes, but can include:

  • a red rash with a circular shape and raised edges
  • cracking, flaking, or dry peeling of the skin in the infected area
  • chafing, irritation, itching, or burning in the infected area

37. Drug allergy

Certain people have allergic reactions to prescribed drugs. The body’s immune system mistakenly attacks the medication as if it were a pathogen. Symptoms vary depending on the individual and the drug, but can include:

  • Rash, including hives
  • Itchy skin or eyes
  • Swelling

38. Atypical pneumonia

Also called walking pneumonia, atypical pneumonia is less severe than the typical form. Symptoms can include:

  • rashes (uncommon)
  • weakness and fatigue
  • chest pain, especially when breathing deeply

39. Erysipelas

Erysipelas is a skin infection. It is a form of cellulitis, however, unlike cellulitis, it only affects the upper layers of the skin, rather than deeper tissue. The skin in a particular area becomes:

  • swollen, red, and shiny
  • tender and warm to the touch
  • red streaks above the affected area

Image credit: CDC/Dr. Thomas F. Sellers/Emory University

40. Reye’s syndrome

Reye’s syndrome is rare and most commonly occurs in children. It can cause serious damage to the body’s organs, particularly the brain and liver (image opposite shows fat accumulation in liver cells). Early symptoms include:

  • Rash on the palms of the hands and feet.
  • Repeated, heavy vomiting.
  • Lethargy, confusion, and headaches.

41. Addisonian crisis

Addisonian crisis – also known as an adrenal crisis and acute adrenal insufficiency – is a rare and potentially fatal condition where the adrenal glands stop working correctly. Symptoms include:

  • skin reactions, including rashes
  • low blood pressure
  • fever, chills, and sweating

42. Chemical burns

Chemical burns are relatively common; they can occur when a person comes in direct contact with a chemical or its fumes. Symptoms vary but can include:

  • skin that appears black or dead
  • irritation, burning, or redness in the affected area
  • numbness and pain

43. Colorado tick fever

Colorado tick fever, also known as mountain tick fever and American tick fever is a viral infection that develops after a bite from a Rocky Mountain wood tick. Symptoms can include:

  • a flat or pimply rash
  • skin or muscle pain
  • fever

44. Accidental poisoning by soap products

Some soap products contain strong chemicals. If they are ingested or inhaled, they can cause serious damage. Symptoms can include:

  • chemical burns on the skin
  • swelling of the throat, lips, and tongue
  • difficulty breathing

45. Adult-onset Still’s disease

Adult-onset Still’s disease is a rare inflammatory disorder that usually affects people in their 30s. Symptoms include:

  • A pink rash, mostly affecting the chest and thighs, which tends to fade quickly.
  • Joint and muscle pain, commonly affecting the knees, wrists, and ankles.
  • Enlarged spleen, liver, or lymph nodes.

46. Juvenile idiopathic arthritis

Juvenile idiopathic arthritis is the most common form of arthritis in children; it used to be called juvenile rheumatoid arthritis. Symptoms vary depending on the subtype, but can include:

  • fleeting rashes
  • a scaly psoriasis-like rash
  • spiking fever

47. Histoplasmosis

Histoplasmosis is a fungal infection of the lungs. Sometimes, it presents no symptoms, but in other cases, it produces pneumonia-like symptoms; these include:

  • rash
  • chest pain
  • red bumps on lower legs

48. Dermatomyositis

Dermatomyositis is a medical condition that causes muscle weakness and rashes. The rash may be red and patchy or bluish-purple in color; it appears in a number of places, including:

  • shoulders and upper back
  • knuckles
  • palms and fingers
  • around the eyes

49. Graft-versus-host disease

People being treated for certain cancers may sometimes undergo a stem cell transplant; in some cases, the donor cells attack the recipient’s healthy cells instead of the cancer cells. Symptoms can include:

  • Rashes affecting the palms of the hands, soles of the feet, ears, or face.
  • Other skin changes, such as drying, scaling, scarring, hardening, and darkening.
  • Hair loss.

50. Icthyosis vulgaris

Ichthyosis vulgaris is a hereditary skin condition that often begins in childhood. It is caused by a mutation in the gene that codes for the protein filaggrin; features include:

  • The skin’s surface becomes dry, thick, and scaly.
  • The dryness is often accompanied by fine, white, or skin-colored scales.
  • It commonly affects the elbows, shins, face, scalp, and torso.

51. Pemphigoid

Pemphigoid is a group of rare autoimmune conditions that primarily cause rashes and skin blistering; there are three main types:

  • Bullous pemphigoid – blistering on the lower torso, groin, armpits, inner thighs, soles, and palms.
  • Cicatricial pemphigoid – mostly affects mucous membranes.
  • Pemphigoid gestationis – develops during pregnancy and mostly affects the upper body.

52. Sarcoidosis

Sarcoidosis is a condition involving the growth of persistent or inappropriate granulomas or clumps of inflammatory cells. Symptoms include:

  • Erythema nodosum – a raised red rash on the lower extremities.
  • Nodules or growths under the skin, especially around scar tissue.
  • Skin discoloration.

53. Phenylketonuria

Phenylketonuria is a genetic condition that affects how phenylalanine is broken down by the body. It affects around 1 in 10,000 babies in the U.S. If left untreated, phenylalanine builds up, causing:

  • skin rashes, such as eczema
  • lighter skin and eyes due to abnormal levels of melanin
  • seizures

54. Porphyria

Porphyria refers to a group of genetic disorders that can affect the nervous system or the skin; symptoms are varied but can include:

  • redness and swelling on the skin
  • burning pain on the skin
  • changes in skin pigmentation

55. Dermatitis neglecta

Dermatitis neglecta is a skin disorder that arises when an individual does not clean themselves sufficiently. It can look similar to other allergic conditions. Symptoms include patches of scaly skin that are collections of:

  • sweat and moisture
  • dirt
  • bacteria and other germs

Image credit: Dr. Piotr Brzezinski Ph.D.

56. Heliotrope rash

Heliotrope rash is often the first noticeable symptom of an inflammatory muscle disease called dermatomyositis. The rash often includes:

  • raised and bumpy skin
  • red patches
  • skin looks dry and irritated

Image credit: Elizabeth M. Dugan, Adam M. Huber, Frederick W. Miller, Lisa G. Rider, 2010.

57. Uric acid skin rash

A person may develop a rash when high levels of uric acid in the blood cause crystals to form and accumulate in and around a joint. This can also lead to gout. Symptoms include:

  • A dotted rash on the surface of the skin
  • Redness, tenderness, and swelling of the joints
  • Prolonged joint pain for weeks following the reaction

Image credit: WNT.

Autoimmune diseases in dermatology

What is the immune system?

The immune system is made up of the cells, molecules, and structures that defend the body from skin infections and monitor for tissue damage .

Immune responses can be divided into innate immunity and adaptive immunity.

Innate immunity

Innate immunity describes generalised measures to ward off infection. These include:

  • Physical barriers, such as the skin and mucous membranes, which stop the majority of microorganisms entering
  • White blood cells, such as macrophages, which recognise microorganisms and release chemicals to stimulate and attract other immune cells
  • Neutrophils, which envelope and digest invading microorganisms by a process called phagocytosis (cellular ‘eating’).

Innate immune responses are often accompanied by inflammation .

Adaptive immunity

Adaptive immunity describes slower immune responses, including the production of immune cells that produce specific antibodies to target and remove a particular microorganism .

  • In cell-mediated immunity, T lymphocytes are produced that are conditioned to eliminate intracellular pathogens (viruses and bacteria) .
  • In humoral immunity, antibody-producing B lymphocytes deal with extracellular pathogens (bacteria in a polysaccharide capsule) .

Adaptive immunity results in the production of memory T lymphocytes (cells that have previously encountered an antigen and have “experience” fighting infections) and B lymphocytes (which produce antibodies) that are able to specifically target a particular infection. These lymphocytes continue to circulate and quickly recognise and remove the particular virus or bacteria when they are next encountered .

What is autoimmunity?

Autoimmunity is an immune response against the self that usually involves T and B lymphocytes. The particular protein or structure targeted by the T and B lymphocytes is called the self-antigen .

Autoimmunity may result in autoimmune disease with tissue damage or impaired physiological function. Autoimmune responses may also occur without causing disease .

Antibodies that react against self-antigens are called autoantibodies. In some autoimmune diseases, autoantibodies are the direct cause of tissue damage. In others, autoantibodies may be present without causing injury .

Examples of autoimmune diseases include:

  • Graves disease (a cause of hyperthyroidism)
  • Rheumatoid arthritis
  • Insulin-dependent diabetes
  • Multiple sclerosis
  • Systemic lupus erythematosus .
Autoimmune skin diseases

Autoimmune blistering skin conditions diseases include:

  • Pemphigus vulgaris and other forms of pemphigus
  • Bullous pemphigoid and other forms of pemphigoid
  • Epidermolysis bullosa acquisita
  • Dermatitis herpetiformis.
Autoimmune bullous diseases

Autoimmunity and deregulation of the immune system also contribute to many skin diseases, such as:

  • Systemic sclerosis
  • Dermatomyositis
  • Psoriasis
  • Vitiligo
  • Alopecia areata
  • Lichen sclerosus.

Who gets autoimmune diseases?

Autoimmune diseases affect around 5% of the population .

  • Most autoimmune diseases are more common in women .
  • People with a family history of autoimmune disease are at higher risk of developing an autoimmune disease themselves .
  • Some studies show autoimmune diseases to be more common among patients from higher socioeconomic groups and northern latitudes .
  • Autoimmune blistering skin diseases are rare and have fairly similar rates in both men and women .

What causes autoimmune diseases?

Autoimmune disease occurs when the responses that normally prevent autoimmunity fail . There are several protective mechanisms.

  • Maturing T lymphocytes in the thymus (a lymphoid organ found between the lungs where the T cells develop and mature) are removed if they react strongly against self-antigens .
  • Circulating T-regulatory cells suppress immune responses .
  • B lymphocytes that react strongly against self-antigens can undergo receptor editing and change their B-cell receptors .
  • T and B lymphocytes in the circulation need co-stimulation by other immune cells to become active .

The exact cause of a particular autoimmune disease is often not fully understood. Risk factors for many autoimmune diseases include genetic factors, infections, hormones, and drugs.

  • Genetic factors are most commonly polygenic (ie, multiple genes combine to increase risk) .
  • Infections may trigger an autoimmune process by mimicking a self-antigen or by increasing co-stimulatory molecules .
  • Genes on the Y chromosome may protect men from autoimmune disease, and oestrogen may play a role in the increased susceptibility of women to autoimmune diseases .
  • Certain drugs (eg, penicillamine, captopril, and vancomycin) can precipitate pemphigus vulgaris and pemphigus foliaceus .

Well-designed trials have concluded that there is no evidence that vaccines cause autoimmune disease .

Autoimmune blistering diseases

The autoimmune cause of this class of blistering skin conditions is confirmed by positive direct immunofluorescence microscopy revealing the deposition of antibodies in the skin.

Pemphigus

Pemphigus is a group of rare blistering disorders caused by circulating autoantibodies that bind to adhesion molecules in the skin, which disrupts keratinocytes from sticking together, causing intraepidermal blisters . The main types of pemphigus are pemphigus vulgaris, pemphigus foliaceus, and paraneoplastic pemphigus .

  • Pemphigus vulgaris is characterised by blisters and erosions inside the mouth as well as on the skin. There are circulating autoantibodies against desmoglein 3, which is a protein important in keratinocyte cell-to-cell adhesion .
  • Pemphigus foliaceus causes superficial blisters typically on the trunk, scalp, and face. There are autoantibodies against desmoglein–1, a molecule that adheres skin cells to each other .
  • Paraneoplastic pemphigus causes blistering and ulceration in the mouth and sometimes the skin; it arises in association with malignancy, most often a non-Hodgkin lymphoma. The multiple autoantibodies seen in paraneoplastic pemphigus include those targeting desmoplakin proteins .

Pemphigoid

The pemphigoid group of diseases includes bullous pemphigoid, mucous membrane pemphigoid, and pemphigoid gestationis. Pemphigoid blisters are subepidermal and are caused by autoantibodies that bind in the area of the dermal-epidermal

junction .

  • Bullous pemphigoid predominantly affects older people who present with large tense fluid-filled blisters and erosions, often preceded by urticated or eczematous plaques . There are antibodies against bullous pemphigoid antigen (BP180), a hemidesmosome-associated protein involved in keratinocyte to basement membrane adhesion, and against bullous pemphigoid antigen 230 (BP230), a protein found in basal keratinocytes .
  • Mucous membrane pemphigoid is characterised by recurrent blistering and ulceration of mucous membranes, particularly in the mouth and eyes, and can also affect the skin . The split occurs lower in the dermal-epidermal junction, leading to scarring. Several autoantibodies have been associated with different presentations of mucous membrane pemphigoid including BP180, BP230, laminin 332, integrin alpha 6 and beta 4, and type VII collagen.
  • Pemphigoid gestationis affects women during pregnancy or shortly after delivery. Pemphigoid gestationis often starts as an intensely itchy urticaria-like rash around the belly button and then may spread to involve the entire skin surface, but not mucous membranes. It later typically progresses to tense blisters resembling those of bullous pemphigoid . BP180 antibodies may be detected. The primary site of autoimmunity is thought to be the placenta.

Other rare blistering diseases

Dermatitis herpetiformis is an itchy blistering skin disease that typically affects the elbows, knees, and buttocks. It is associated with coeliac disease and the symptoms heal with a gluten-free diet . It is characterised by blisters with a subepidermal deposition of immunoglobulin A (IgA) and a neutrophilic infiltrate. In dermatitis herpetiformis, the antibodies in the autoimmune response target the coagulation enzyme epidermal transglutaminase .

Linear IgA bullous dermatosis is a very rare autoimmune blistering disorder that can be acquired or drug-induced (eg, by vancomycin). The blisters are sometimes arranged in rings (known as the ‘pearl necklace’ sign) . There is subepidermal deposition of IgA antibodies which target a portion of the BP180 antigen, type VII collagen, or other basement membrane proteins.

Epidermolysis bullosa acquisita is also very rare. In its classical form, blisters and erosions form at areas of minor trauma . In epidermolysis bullosa acquisita, the autoimmune reaction is directed against type VII collagen in the basement membrane zone of the skin and mucosa.

Bullous systemic lupus erythematosus is a rare presentation of subepidermal blistering in a patient with systemic lupus erythematosus.

How are autoimmune diseases in dermatology diagnosed?

A biopsy is usually needed for a definitive diagnosis of autoimmune skin disease, although a characteristic appearance may be suggestive of a particular condition .

Blood tests may include:

  • Tests for circulating skin autoantibodies (indirect immunofluorescence)
  • Tests for coeliac antibodies, such as IgA tissue transglutaminase antibodies
  • Nonspecific tests for inflammatory markers (eg, C-reactive protein)
  • An autoimmune screen (eg, anti-nuclear antibodies).

Swabs may be taken of a ruptured blister to look for signs of a bacterial infection or herpes virus infection.

What is the differential diagnosis for autoimmune blistering skin diseases?

Blistering skin rashes associated with systemic illness may present with fever and ‘flu-like’ symptoms . These disorders can include:

  • Steven–Johnson syndrome / toxic epidermal necrolysis
  • Staphylococcal scalded skin syndrome
  • Varicella-zoster infection
  • Disseminated herpes zoster, eczema herpeticum, or herpes simplex in immunocompromised patients
  • The bullous form of systemic lupus erythematosus
  • Acute febrile neutrophilic dermatosis.

Other generalised blistering disorders that present with autoimmune skin disease symptoms include:

  • Bullous impetigo
  • Miliaria crystallina .

The blistering of mucous membranes is also a common symptom in these conditions:

  • Erythema multiforme
  • Viral skin infection (eg, herpes simplex, herpes zoster, or enteroviral stomatitis)
  • Aphthous ulcers
  • Behçet syndrome .

What is the treatment for autoimmune skin diseases?

The treatment of autoimmune skin diseases depends on the specific condition.

Pemphigus and pemphigoid are mainly treated with systemic corticosteroids and immunosuppressive treatments .

Dermatitis herpetiformis is treated with dapsone and a gluten-free diet .

Autoimmune Skin Disorders

The body reacts in a variety of ways to autoimmune disorders, which cause a person’s immune system to attack its own tissues.

Depending on the condition, an autoimmune disorder can affect a variety of organs, joints and muscles, or other bodily tissues. One tissue that’s commonly affected by autoimmune disorders is the skin.

There are many different types of skin-related autoimmune disorders, including scleroderma, psoriasis, dermatomyositis, epidermolysis bullosa, and bullous pemphigoid.

Scleroderma. The skin is just one area that is affected by scleroderma, which is actually a widespread condition that affects all of the body’s connective tissue. Since this autoimmune disorder extends throughout the body, patients can experience not only skin changes, but also symptoms in blood vessels, muscles, and organs. A localized form of scleroderma results in patches of thickened skin, while systemic scleroderma is the form that has the greatest impact on people’s lives.

There are two forms of systemic scleroderma: progressive systemic sclerosis (PSS), sometimes known as just systemic sclerosis (SS), and CREST syndrome. Patients with systemic scleroderma may experience symptoms that affect that the esophagus, intestines, lungs, heart, and kidneys. CREST syndrome is named after its symptoms: calcinosis (calcium accumulation under the skin), Raynaud phenomenon (redness or blueness of fingers and toes), esophageal dysfunction, sclerodactyly (thickening and tightness of the skin that surrounds the fingers and toes), and telangiectasia (red skin blotches causes by dilated blood vessels). In addition to the skin symptoms caused by scleroderma, patients may experience joint pain, shortness of breath, wheezing, constipation or diarrhea, bloating, weight loss, heartburn, or eye itching and burning.

Men and women are both at risk for scleroderma, but the majority of cases occur in women in their thirties and forties. Occupational exposure to silica dust and polyvinyl chloride are considered risk factors for this autoimmune disorder. According to the Scleroderma Foundation, an estimated 300,000 people in the United States live with scleroderma; about 33 percent of them have the systemic type.

Psoriasis. Psoriasis is a chronic autoimmune disorder that manifests as skin redness and irritation. There are five different types of psoriasis: guttate, plaque, inverse, erythrodermic, and pustular. The most common is plaque psoriasis, in which raised, red skin patches are covered by flaky, silver-white patches of dead skin, known as scales. Current research indicates that psoriasis is most likely an inherited disorder — commonly, psoriasis patients have a family member with the same disease or another autoimmune disorder.

Psoriasis symptoms can come and go through a person’s life. Episodes of this autoimmune disorder may be triggered by infections, skin injuries, sun exposure, medications, alcohol, or even stress. People whose immune systems are already compromised, such as those with HIV or undergoing chemotherapy, are at risk for more severe attacks of psoriasis.

The National Institutes of Health reports that approximately 7.5 million Americans are living with psoriasis. Usually, signs of this autoimmune disorder appear between the ages of 15 and 35, although people of all ages can be affected. An estimated 30 percent of people with psoriasis also have arthritis — a condition known as psoriatic arthritis.

Dermatomyositis. This autoimmune disorder is primarily muscular in nature, but because dermatomyositis also affects the skin, it is sometimes categorized with skin-related autoimmune conditions. Dermatomyositis goes hand-in-hand with polymyositis, an autoimmune disease that causes muscle weakness, soreness, and stiffness. Patients with these conditions also may experience difficulty swallowing and shortness of breath. Dermatomyositis and polymyositis share these symptoms, but dermatomyositis is distinguished by a skin rash, normally on the upper body, as well as thickening and tightening of the skin in many areas. Dermatomyositis patients may also have purple colored eyelids.

Childhood dermatomyositis is differentiated from the adult form, with symptoms including fever, fatigue, rash, and weakness. In children, the disorder normally shows up between the ages of 5 and 15, and in adults, people 40 to 60 are most at risk. The condition is more prevalent among women.

Epidermolysis bullosa.There are many forms of epidermolysis bullosa, but only one, epidermolysis bullosa acquisita, is considered autoimmune in nature. All forms of epidermolysis bullosa cause fluid-filled skin blisters to develop in response to injuries that don’t normally warrant that type of reaction. For example, gentle rubbing of the skin or even an increase in room temperature can cause blisters to form.

Diagnosing the correct form of epidermolysis bullosa can be challenging. However, one distinguishing characteristic of epidermolysis bullosa acquisita is that it normally doesn’t develop until later in life — after age 50 — while non-autoimmune forms of epidermolysis bullosa typically show up at birth or soon after. The condition can still be difficult to diagnose, because it’s hard to differentiate from mucous membrane pemphigoid, another autoimmune disorder characterized by blistering.

Bullous pemphigoid. This chronic autoimmune disorder involves skin blisters that range in severity. In some cases, the patient may experience only mild redness or irritation of the skin, while other, more severe cases involve multiple blisters that can break open and form ulcers. Bullous pemphigoid patients normally develop blisters on their arms, legs, or torso, and in about one-third of cases, blisters form in the mouth. Some but not all people with this condition also experience itching and bleeding gums.

Cases of bullous pemphigoid have been reported in all age groups, but the disorder most commonly affects the elderly. Men and women are equally at risk for bullous pemphigoid. It is difficult to pin down the incidence of this disease because symptoms come and go, with many patients seeing the condition completely disappear after six years. One estimate is that roughly 5 or 10 new cases of bullous pemphigoid are seen in a typical large hospital each year.

If you have symptoms of any of these autoimmune disorders of the skin, see your doctor. She can help you determine what is causing your symptoms and start you on the appropriate treatment.

Rare Disease Database

The skin is the largest organ of the body. In addition to serving as a protective barrier, the skin is involved in many additional functions of the body such as regulating internal body temperature. Five distinct layers make up the skin; each layer is filled with specialized cells. The two main structural layers of the skin are the epidermis – the outermost, protective layer of skin – and the dermis – an underlying layer that contains numerous specialized cells, tissues and structures. Specialized proteins and structures are required for the dermis and epidermis to stick together. When the epidermis separates from the dermis a blister (bulla) may form.

A blister can be either tiny or large and consists of a fluid-filled bubble that forms underneath the surface of damaged or dead skin. Most blisters develop in response to irritation or injury of the skin. In autoimmune blistering diseases, blisters form because the body creates antibodies that attack certain proteins required for the proper health and function of the skin. In many cases, blisters can rupture becoming open sores or wounds.

In some autoimmune blistering diseases, blisters or lesions can also form on the mucous membranes, the thin, moist coverings of many of the body’s internal surfaces. Mucous membranes line the esophagus and anus, the inside of the mouth, the nasal passageways, the genitals and the throat. Associated symptoms depend on the location of blister formation, but can include gastrointestinal bleeding, difficulty swallowing or difficulty breathing.

There are several different categories of autoimmune blistering diseases including pemphigus, pemphigoid, IgA-mediated dermatoses and epidermolysis bullosa acquista. Pemphigus, pemphigoid and IgA-mediated dermatoses can be further broken down into additional subtypes.

Pemphigus
The term pemphigus is a general term for a group of related autoimmune blistering diseases. The two main types of pemphigus are pemphigus vulgaris and pemphigus foliaceus. Each type has additional subtypes.

Pemphigus vulgaris is the most common form of pemphigus. It is characterized by blisters that rupture easily and cause painful erosions. In most cases, pemphigus vulgaris first develops in the mouth, followed by blistering of the skin. Any area may potentially be affected. The blisters are usually not itchy.

Pemphigus foliaceus is characterized by multiple small, blisters that quickly break apart to form itchy (pruritic), scaly, crusted lesions that affect the uppermost layer of the skin. The scalp and face are usually affected first. Eventually, the chest, upper back may become involved. The lesions are usually not painful. The mucous membranes are usually not affected.

Additional disorders are sometimes classified as subtypes of pemphigus including paraneoplastic pemphigus and pemphigus IgA. Some physicians consider these disorders similar, yet distinct, autoimmune blistering diseases.

Paraneoplastic pemphigus is a rare disease that occurs in individuals who have cancer, especially blood (hematologic) cancers such as leukemia or lymphoma. Paraneoplastic pemphigus is characterized by painful lesions affecting the mucous membranes, especially those found in the mouth and the lips. The mucous membrane lining the inside of the eyelids (conjunctiva) is also frequently affected. In other cases, the lesions can affect the linings of the gastrointestinal or respiratory tracts and potentially cause life-threatening complications. In some cases, lesions affecting the skin may develop. These lesions may vary from case to case and may appear as small, reddened bumps (erythematous macules), non-firm (flaccid) blisters, scaly plaques, pustules, or erosions.

Pemphigus IgA, also known as intraepidermal neutrophilic IgA dermatosis, is characterized by the development of fluid-filled blisters on the skin. The mucous membranes are usually not affected. In most cases, the trunk and the upper arms or legs are affected. The scalp can be extensively affected in some people.

Pemphigoid
Pemphigoid is a general term for a group of related diseases characterized by blistering skin eruptions. The main forms of pemphigoid are bullous pemphigoid, mucous membrane pemphigoid, and pemphigoid gestationis.

Bullous pemphigoid is a chronic skin disease usually affecting the elderly that is characterized by firm, large blisters that develop on normal-appearing or reddened skin on the trunk or skin folds, sometimes around cuts or scars. Within weeks, blisters often spread to the groin, armpit, abdomen, and the skin where muscle contracts or flexes (flexor muscles). In some cases, the lesions may become widespread covering a significant portion of the skin and blisters may form inside the mouth. In most cases, the mucous membranes are not affected and, when they are, they tend to heal quickly. The lesions of bullous pemphigoid are often associated with intense itching.

Mucous membrane pemphigoid (MMP) is a rare group of chronic autoimmune diseases characterized by blistering lesions that primarily affect the various mucous membranes of the body. The mucous membranes of the mouth and eyes are most often affected. The mucous membranes of the nose, throat, genitalia, and anus may also be affected. The symptoms of MMP vary among affected individuals depending upon the specific site(s) involved and the progression of the disease. Blistering lesions eventually heal, sometimes with scarring. Progressive scarring may potentially lead to serious complications affecting the eyes and throat. In some cases, blistering lesions also form on the skin, especially in the head and neck area. Mucous membrane pemphigoid has been known by many different names within the medical literature including benign mucous membrane pemphigoid, cicatricial (scarring) pemphigoid, and ocular cicatricial pemphigoid.

Pemphigoid gestationis occurs in women during pregnancy or shortly after birth (postpartum period). Affected individuals develop reddish bumps or hives usually around the navel (umbilicus) and the arms and legs. The rash may spread to affect other areas of the body and may be extremely itchy. Eventually, the skin lesions progress to form blisters. Pemphigoid gestationis usually resolves within three months without treatment (spontaneously).

IgA Mediated Bullous Dermatoses
IgA-mediated bullous dermatoses are disorders characterized by elevated levels within the body of a specialized protein known as immunoglobulin A (IgA). In these disorders, IgA has a particular tendency to accumulate in the skin. Dermatitis herpetiformis and linear IgA disease are IgA-mediated bullous dermatoses. When liner IgA disease affects children, it may be known as chronic bullous disease of childhood.

Dermatitis herpetiformis, also known as Duhring disease, is characterized by red clusters of extremely itchy (pruritic) blisters. The elbows, knees, scalp and buttocks are most often affected. The mucous membranes are rarely involved. The symptoms of dermatitis herpetiformis tend to come and go. Most cases of dermatitis herpetiformis are associated with Celiac disease, a digestive disorder characterized by intolerance to dietary gluten, which is a protein found in wheat, rye and barley.

Linear IgA disease is characterized by blistering eruptions on the skin. The elbows, knees and buttocks are most often affected. New blisters may arise in areas where older blisters are – a finding that creates a small group of blisters that may be described as a “cluster of jewels”. In some cases, itching (pruritis) may be develop and may occur before the development of skin lesions. In approximately 50 percent of cases the mucous membranes are affected as well, especially the mucous membranes of the mouth and eyes. Eye involved can cause blurred vision, irritation, light sensitivity, and corneal scarring.

Epidermolysis Bullosa Acquista
Epidermolysis bullosa acquista is a rare autoimmune disorder of the skin that typically affects middle-aged and elderly people. The skin of affected individuals is extremely fragile. Trauma to the skin can cause blisters to form. The elbows, knees, pelvis, buttocks, and/or scalp are most often affected. Increased levels of a specialized protein known as immunoglobulin G are usually found around the blisters. After the blisters heal, scars and small white bumps or cysts (milia) may remain. The mucous membranes are rarely involved. A subset of patients with epidermolysis bullosa acquista has a widespread, inflammatory form of the disorder that develops rapidly and often involves the mucous membranes.

Vascular, Lymphatic and Systemic Conditions

Systemic lupus erythematosus (SLE) is an autoimmune condition that affects mostly women beginning in their 20s or 30s. Autoimmune disease occurs when the immune system attacks the body’s own tissues. Lupus may affect almost every organ and system in the body including the skin, heart, lungs, blood vessels, nervous system, joints, and kidneys. A combination of genetic and environmental factors is believed to play a role in triggering lupus. The disease may be progressive or undergo periods of remission. Potential triggers include viruses, sunlight, and allergies to medications. People of Asian and African American descent are more likely to get lupus than individuals in other ethnic groups. They may also be more likely to suffer from more severe cases of lupus.

Lupus is diagnosed when four of the following 11 criteria are present in a patient:

  • Malar “butterfly” rash across the nose and cheeks
  • Rash consisting of raised red patches (discoid rash)
  • Rash resulting from sensitivity to the sun (photosensitivity)
  • Ulcers in the nose or mouth
  • Two or more joints affected by arthritis with swelling, tenderness, or effusion
  • Inflammation of the heart (pericarditis) or lungs (pleuritis)
  • Neurological symptoms like seizures or psychosis
  • Kidney problems including excess protein in the urine or reduced kidney function
  • Positive antinuclear antibody (ANA) test
  • Presence of antibodies such as antiphospholipid antibodies, anti-double-strand DNA, or anti-Smith antibodies

Presence of abnormalities in blood counts (low white blood cells, low platelets, or anemia)

Dermatology – Autoimmune Skin Diseases

Autoimmune Skin Diseases

Autoimmune connective tissue diseases such as lupus erythematosus, dermatomyositis, and scleroderma are chronic conditions often associated with skin findings such as rashes, sun sensitivity, hair loss, mouth sores, or nail changes. For some patients, the skin is the only or the most severely affected organ, while for others, the skin is one of many organs affected. Skin changes are often among the earliest signs of these diseases. The cause of these diseases is unknown.

Dermatologists perform complete skin examinations to detect early signs of autoimmune connective tissue diseases. Skin biopsies and/or laboratory testing may be performed to aid in making the diagnosis and to monitor for evidence of internal organ damage associated with these diseases.

Treatment of the skin manifestations of lupus erythematosus, dermatomyositis, and scleroderma must be tailored to the individual patient and frequently involves both topical and systemic medications. You will be closely monitored for medication side effects and signs of systemic manifestations of your condition. Your dermatologist will work closely with other physicians involved in your care to ensure that you are receiving the safest and most effective therapy.

Learn more about autoimmune diseases.

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