Introduction

Linear immunoglobulin A (IgA) dermatosis (LAD) is an autoimmune condition in which there is a linear deposition of IgA at the basement membrane zone. The disease affects both children and adults. It may be drug-related or non drug-related. In the non drug-related category the cause is mostly unidentified. However, several cases have been reported following an episode of infection (eg typhoid, brucella, tuberculosis, varicella, herpes zoster, gynaecological infections, upper respiratory infections). In children, the condition has been known historically as chronic bullous dermatosis of childhood.

Histopathology

LAD is an autoimmune disease histopathologically characterised by the linear deposition of IgA at the basement membrane zone (BMZ). One function of the BMZ is to maintain the contiguity of the dermal-epidermal junction; antibody deposition causes complement fixation and neutrophil chemotaxis (rapid migration of neutrophils to sites of inflammation), eventually resulting in blister formation.

Antibody deposition leads to complement activation and neutrophil chemotaxis, which eventuates in loss of adhesion at the dermal-epidermal junction and in blister formation. At the molecular level, a variety of antigens have been identified, some of which are also seen in patients with bullous pemphigoid. LAD may thus be an umbrella term for a wide range of conditions, each involving a different antigen; however, further research is needed. ^[1]

The immune pathology appears to be identical in adults and children.

Epidemiology^[1]

This is a rare condition.The incidence in adults in southern England has been estimated to be 1 case in 250,000 population per year. There are no figures for the incidence in children. Some studies have reported a slight preponderance of women.

The distribution of the age of onset seems to follow a bimodal pattern. In children, the age range is from 6 months to 10 years, with a mean of 3.3-4.5 years. In adults, the range is from 14-83 years with a mean of 52 years. Drug-induced disease is more prevalent in older people, probably because they are most likely to be on medication.

Presentation^[1][2][3]

History

Before the appearance of the rash, there may be chronic pruritus or acute itching or burning. Patients developing ocular lesions may initially note pain, grittiness or discharge.

As with any patient presenting with a rash, a detailed medication history should be taken. The rate of spread of the blisters is variable. They tend to appear quickly in drug-induced cases. In vancomycin-induced cases the onset ranges from 1-13 days after the first dose.

Examination

Several skin presentations may occur:

• Clear round or oval blisters on normal underlying skin
• Small blisters (vesicles) or large ones (bullae), often target-shaped, surmounting an erythematous area of skin which is flat or raised
• New vesicles developing in a ring around the old one (the 'string of beads' sign)
• A crop of vesicles developing close together ('cluster of jewels' sign)
• Crusts, scratch-marks, sores and ulcers
• Lesions which mimic erythema multiforme, bullous pemphigoid and dermatitis herpetiformis.
• 50% of patients have blisters and ulcers around the mouth and lips
• Ophthalmological findings may include subconjunctival fibrosis and shrinkage of the fornices

The distribution of the skin lesions varies between children and adults. Children tend to get them on the lower abdomen, anogenital areas, perineum, hands, feet and face. In adults, lesions tend more commonly to develop on the trunk and limbs. In both age groups the distribution may be symmetrical or asymmetrical.

Differential diagnosis

A number of skin conditions have an almost identical appearance. These include:

• Bullous pemphigoid
• Dermatitis herpetiformis
• Lupus erythematosus
• Epidermolysis bullosa acquisita

Investigations^[1][2][3]

• Histopathology of a skin biopsy shows subepidermal blistering, differentiating the condition from diseases in which blistering occurs within the epidermis (eg pemphigus).
• Direct immunofluorescence reveals IgA deposition along the basement membrane.
• Serum IgA levels may be raised but this occurs more often in the childhood version.
• Techniques to identify individual antigens within the BMZ are available but these are more research tools than diagnostic investigations.

Associated diseases^[3]

• Chronic renal failure
• Immune complex glomerulonephritis
• Lymphocytic colitis
• Lymphoma
• Other malignant tumours
• Psoriasis
• Rheumatoid arthritis
• Sarcoidosis
• Ulcerative colitis

Associated drugs

• Amiodarone
• Atorvastatin
• Captopril
• Cefamandole
• Ceftriaxone
• Furosemide
• Glibenclamide
• Interleukin-25
• Lithium carbonate
• Metronidazole
• Non-steroidal anti-inflammatory drugs
• Penicillin
• Phenytoin
• Somatostatin
• Trimethoprim-sulfamethoxazole
• Vancomycin

Management^[1][2]

Ruptured lesions and erosions may require sterile dressings. Large bullae do not require any particular treatment if intact. Infection lesions should be treated with topical mupirocin and sterile dressings twice-daily.
Dapsone or sulfapyridine are the treatments of choice for non drug-related dermatitis. Sulfapyridine causes fewer adverse effects but is not as effective as dapsone in all cases.
Other treatments which have been reported to help some patients include:

• Corticosteroids (prednisone or prednisolone)
• Tetracycline antibiotics
• Erythromycin
• Colchicine
• Mycophenolate mofetil
• Intravenous immunoglobulins

In drug-related disease, removal of the offending drug usually results in resolution, although this can take up to two weeks. Corticosteroids have been required to hasten resolution in severe cases.

Hospital referral

• Dermatological referral will be required for the initial diagnosis.
• An ophthalmological opinion will be required once diagnosis has been made, irrespective of whether the patient has any eye symptoms, as changes may be detected on examination (eg subconjunctival fibrosis) before complications arise.

Complications^[1]

Complications are usually the result of scarring. Lesions on the gums can result in desquamative gingivitis resulting to damage to the teeth. Ocular linear IgA may mimic cicatricial pemphigoid and lead to blindness. There have been reports of involvement of the pharynx, larynx, nose, rectum and oesophagus.

Prognosis^[1]

In children, most idiopathic cases resolve within two years. In adults the disease is more protracted. Resolution does eventually occur; the mean duration is 5.6 years but it has been known to last for 15 years. The condition tends to wax and wane in severity.

One study of twelve women found that the condition was improved during pregnancy. No fetal damage was found as a result of the treatment (dapsone) or the disease.