Linear immunoglobulin A (IgA) dermatosis is also referred to as Linear IgA Bullous Disease (LABD or LAD). The childhood version is called Linear IgA Bullous Disease of Childhood (LABDC), and is immunologically identical to the adult disease.
Drug-induced cases resolve once the causative drug is withdrawn. The most common causative agent for LAD is Vancomycin. Seventeen case reports have implicated vancomycin in LAD. Of all reported causative drugs, it is the best-documented agent in the literature. Other potential triggers and their respective number of published case reports (listed in parentheses) include the following:
Onset may be slow and insidious but is more usually sudden. Symptoms vary from mild to severe pruritis (itching), accompanied by a burning sensation, and blisters. Contact from such articles as clothes, labels, shoes, waistbands and spectacles can cause blistering. Surgery and medical procedures also excite blistering, for example, use of airway apparatus during anaesthesia, skin biopsies, dental work or pap smears. As with most autoimmune diseases, patients report tiredness, with some patients also reporting fevers and digestive problems.
Clinically, LAD has a heterogeneous (mixed) presentation, the lesions comprising urticated plaques, papules and vesicles and blisters. Blisters can arise from normal skin and from urticated plaques. Blisters appear in two distinct ways, either in a linear presentation like a string of beads, or in a ring. Once the first blister has scabbed over, a second ring of blisters will form around it, forming the “crown of jewels” effect. Blisters can vary in size from small (2mm in diameter) to much larger (up to about 5 cm). They can be tense and full of clear fluid, or reddish lumps.
LAD affects all types of skin including mucous membranes. Mucosal involvement is common, causing ulcers and erosions and can involve the mouth, gums, (thereby damaging teeth), pharynx, larynx, nose, rectum, vagina, oesophagus and eyes.
Lesions in mucous membranes heal with scarring and therefore pose considerable morbidity, as scarring in this type of tissue continues to grow, and can cause serious problems if in the throat or gullet, and if in the eyes, blindness. Cutaneous lesions normally heal without scarring.
Hoarseness is an indication of throat involvement; stuffiness, crustiness and bleeding an indication of nasal involvement. Involvement of the eyes is different and far more serious, in that changes, such as fine scarring, may be present in the absence of ocular complaints and can lead to blindness. The progression of ocular LAD can prove to be rapid and is indistinguishable from Cicatricial Pemphigoid.
The mean duration of idiopathic LAD of childhood is 3.9 years, ranging from 2.1-7.9 years, and remission has been reported to occur in approximately 64% of these cases within 2 years.
LAD in adults can commence at any age from post puberty to the ninth decade, most commonly occurring after the age of 60 years. It can last for anywhere between 1-15years, and the remission rate is much less than in children, around 48%. The disease tends to wax and wane in severity and is totally unpredictable.
The immune system is the body's secret army, protecting the body from invasion from bacteria, viruses, fungi, etc. All the cells in the immune system come from the same basic stem cells in the bone marrow, and they in turn produce white blood cells called lymphocytes. These fall into two categories: B lymphocytes and T lymphocytes. It is the B lymphocytes that are involved in this disease.
B Lymphocytes are made in the bone marrow and produce antibodies, also called immunoglobulins. These antibodies are large proteins, not cells. Invading bacteria and virus cells have proteins on their surfaces (as do all cells) called antigens, and antibodies can recognise intruders and latch onto them and destroy them.
There are five groups of antibodies: IgG, IgA, IgM, IgE and IgD, with IgG and IgM being most involved in fighting infection. It is the IgA antibody in LAD that is abnormal.
Every line of defence is heavily reliant on good communication between its commanders and officers, and the immune system is no exception. It has chemical messengers known as cytokines, which tell the immune cells when they need to attack and when they may leave.
When the immune system malfunctions and attacks its own body tissues, it produces abnormal antibodies, called autoantibodies. This response is called an autoimmune reaction, which results in inflammation and tissue damage. In the case of LAD, the IgA autoantibody attacks a normal protein (found in all human skin), which is in the lower layer of the epidermis, (the outer layer of skin) known as the BMZ. These proteins are important in maintaining the integrity of skin, and when the autoantibody binds with this protein it causes the cells to come apart (acantholysis) leading to fluid accumulation between layers of skin and forms blisters, which are the manifestation of the disease. The target antigen for LAD is as yet unidentified.
The exact mechanisms causing these changes are not fully understood, but scientists are working to understand the events that precede the production of the antibody, and what causes the IgA antibody to be abnormal. The cells that control antibody production, (B lymphocytes - a type of white blood cell) may malfunction and produce this IgA antibody abnormally (now referred to as an IgA autoantibody).
It is accepted that individuals having this disease possess a genetic make-up that renders them susceptible to the disease, and it is theorized that the inflammation initiated by bacteria, viruses, toxins, some drugs and other environmental agents may play a role in provoking or triggering the autoimmune response, in someone who is genetically predisposed to develop such a disorder.
Linear IGA disease cannot be cured or made to “disappear” with treatment. Treatment is a drug regime designed to suppress the immune system.
Specialised treatment is required for all aspects of this disease: dermatologists who specialise in bullous diseases, pathology blood reports to monitor drug side effects, dentists, endocrinologists and, in particular, ophthalmologists, all of whom monitor the patient closely and at regular intervals. A general practitioner is usually the coordinator of the treatment regime, referring the patient to various specialists and monitoring side effects of the drug regime.
The goals of treatment are control of the autoimmune reaction by balancing the suppression of the immune system, reducing the symptoms of the autoimmune process to self-tissues, while maintaining the body’s normal immune response to infection.
The mainstay of the treatment regime is corticosteroids and dapsone or sulfasalazine. If this is not satisfactory, corticosteroids are added to a long-term immunosuppressant and, sometimes, an antibiotic.
Corticosteroids such as prednisolone or prednisone are used as short term immunosuppressants and anti inflammatories, at the start of treatment, or if symptoms become worse. Once the long term immunosuppressants take effect, corticosteroid doses can be reduced. It is seen as desirable to reduce the prednisone as it has more toxic side effects than the long term immunosuppressants.
Dapsone is usually combined with the corticosteroids. Sulfasalazine is sometimes used as an alternative to dapsone.
Some long-term immunosuppressant drugs used in the treatment of LAD are Dapsone, Cyclophosphamide, Cyclosporine, Azathioprine, or Methotrexate. These are usually administered in conjunction with prednisone. An additional antibiotic may also be prescribed. The antibiotics are used for their anti-inflammatory effects.
Intravenous immunoglobulins may also be used in treatment.
Drugs used to control the autoimmune reaction (immunosuppressants) interfere with the body’s ability to fight disease, the drugs suppressing not only the autoimmune reaction but also the body’s ability to defend itself from microorganisms that cause infection and cancer cells. All of these drugs have side effects, which in themselves may require additional treatment, such as calcium supplementation to reduce bone thinning, Omeprazole (Acimax) to prevent possible stomach ulcers and/or bleeding from corticosteroids, and Vitamin E 800mg to reduce dapsone-induced headache. Anti-fungal medication may also be necessary as immunosuppressed patients are vulnerable to fungal infections.
Topical steroids are usually prescribed to relieve itching and to dry up sores left by blisters. Wet dressing treatment using topical steroids may be used to control bad outbreaks of lesions. This treatment increases absorption of the steroid cream to lower levels of the skin and helps prevent blister formation.
Patients on these drug regimes require close monitoring via regular blood tests, blood pressure monitoring and weight monitoring.
Controlling and minimising the severity of the outbreaks is the goal of treatment. Some cases report total remission periods of the disease, but these reports are mainly confined to younger patients. Childhood LABDC may go into complete remission before puberty.