Inflammatory Diseases of the Skin
Moderator: Dr. Lorenzo Cerroni
Case 7 -
Linear IgA Bullous Dermatosis Due to Vancomycin Therapy
James W. Patterson, M.D.
Linear IgA disease for a time was considered a variant of dermatitis herpetiformis, as there are
(sometimes) clinical as well as histopathologic resemblances. However, it is now considered a separate
condition with a different set of target antigens and immunopathology and a lack of association with
gluten sensitive enteropathy. Linear IgA disease is generally divided into two types: a juvenile form,
sometimes termed chronic bullous dermatosis of childhood, and an adult
variety. In the juvenile type, large tense blisters occur, particularly in the periorbital and genital
regions or on the lower abdomen. Polycyclic arrangements of blisters are sometimes referred to as
"clusters of jewels". Remission occurs over several months or years. The adult variety can resemble
bullous pemphigoid, dermatitis herpetiformis, or other bullous dermatoses and has a different
distribution pattern, with common involvement of trunk, extremities, and mucous membranes. Underlying
disease associations in adult cases include colitis, rheumatoid arthritis, and lymphoma or other
malignancies. However, drug is a particularly common triggering factor. Antimicrobial agents are
leading causes, and vancomycin is among the best known of these. Other implicated drugs include
captopril, atorvastatin, carbamazepine, diclofenac, naproxen, piroxicam, and lithium. Bullae develop
several days to two weeks following exposure to the drug and heal several weeks after discontinuation of
the offending agent.
Case 7 - Slide 1
Microscopically, papillary neutrophilic microabscesses are found, as seen in dermatitis herpetiformis,
some examples of pemphigoid, epidermolysis bullosa acquisita, and bullous lupus erythematosus. A few
eosinophils can be identified, but neutrophils tend to predominate. Few differences from these other
disorders can be seen, although foci of subepidermal separation tend to be larger than those in
dermatitis herpetiformis, and neutrophilic infiltration tends to be more diffuse and not necessarily as
concentrated at tips of dermal papillae. Definitive diagnosis is dependent upon direct immunofluorescent
study, which shows linear IgA deposits along the basement membrane zone. IgA is the only immunoglobulin
in about 80% of cases. When other immunoglobulins are also present, IgA staining is strongest in cases
of linear IgA disease. However, when C3 is also present in cases that express more than one
immunoglobulin, consideration should be given to other immunobullous disorders, such as bullous
pemphigoid. Circulating IgA directed to basement membrane components can be identified by indirect
immunofluorescence in some cases.
The target antigens in drug-induced cases of linear IgA disease are heterogeneous, and can be located
in the upper lamina lucida (resembling bullous pemphigoid) or the sublamina densa zone (resembling
epidermolysis bullosa acquisita). This has also been reflected in the findings on immunoelectron
microscopy. In the majority of cases, characterization reveals 97 kd (ladinin) or 120 kd (LAD-1)
antigens, degradation products of the 180 kd bullous pemphigoid antigen. In a smaller number of cases
with target antigens in the sub-lamina densa zone, the NC-1 domain of type VII collagen appears to be
involved. This may explain why some cases of linear IgA disease have a clinical picture more closely
resembling epidermolysis bullosa acquisita. It appears that "linear IgA disease" may actually consist of
several different disorders that share basement membrane zone IgA deposition.
- Armstrong AW, Fazeli A et al: Vancomycin-induced linear IgA disease manifesting as bullous erythema multiforme. J Cutan Pathol 2004; 31: 393-397.
- Leonard JN, Haffenden GP et al: Linear IgA disease in adults. Br J Dermatol 1982; 107: 301-316.
- Mutasim DF, Cummings MP: Linear IgA disease with clinical and immunopathological features of epidermolysis bullosa acquisita.
- Paul C, Wolkenstein P et al: Drug-induced linear IgA disease: target antigens are heterogeneous. Br J Dermatol 1997; 136: 406-411.