Page 895 - Clinical Immunology_ Principles and Practice ( PDFDrive )

866 Part SEVEN Organ-Specific Inflammatory Disease

in patients with progressive ocular MMP whose vision is threat- monomeric and not of gut origin. Immunoelectron microscopy
ened. In some patients, IVIG has arrested the progression of eye most often reveals IgA deposits in the lamina lucida; but IgA
disease, maintaining vision and preventing blindness. However, deposits have also been seen below the lamina densa. Circulating
no controlled studies have yet been performed. Case reports IgA antibodies against the basement membrane zone of stratified
suggest some benefit with plasmapheresis, etanercept, and squamous epithelium are detected in only 10–30% of both adult
infliximab. Growing numbers of case series have suggested that and pediatric patients with linear IgA deposits. Other immuno-
rituximab may effective, with most patients showing complete reactants, especially IgG and C3, have been found in 30–40%
response after a single course, but, again, no controlled trials of patients.
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have been published. A retrospective study of MMP patients
given rituximab showed that all patients achieved disease control, Pathogenesis
compared with 40% of those who received conventional therapy. 48 The paucity and heterogeneity of circulating antibody has made
The clinical course of MMP is difficult to predict, and the it difficult to determine the antigenic target in LABD. Sera from
response to treatment is often suboptimal. Some patients achieve adults and children with linear IgA deposits within the lamina
long-lasting remissions, but MMP frequently recurs, and patients lucida reacted with a 97-kDa protein that is identical to part of
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in remission should be monitored closely. BPAG2. In patients with LABD or linear IgA disease of childhood
Ocular mucosal lesions are often severe in MMP and can with IgA deposits below the lamina densa, antibodies have been
cause significant morbidity. Consultation with an ophthalmologist identified reactive to type VII collagen and an unknown 285-kDa
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is important in managing the potentially severe ocular complica- dermal protein. These findings support the hypothesis that
tions. Physicians should also be aware of the risk of esophageal there are heterogeneous target antigens in LABD and linear IgA
and tracheal involvement; patients with severe disease often need disease of childhood. Regardless of the location of IgA deposits
consultation with relevant specialists. Oral mucosal lesions can or the specific antigenic target, the mechanism of lesion formation
often be managed with frequent application of potent topical in patients with LABD remains unknown.
corticosteroids (0.05% clobetasol propionate or 0.05% fluoci-
nonide). In severe cases, dapsone or systemic glucocorticoids Therapy
may also be needed. Patients with limited skin disease can often Dapsone (25–200 mg/day) is the mainstay of therapy of patients
be managed with topical therapy alone. If this fails, treatment with all forms of LABD. Although dapsone is well tolerated by
as for BP is usually successful. most patients, it has significant pharmacological and idiosyncratic
adverse effects. Occasionally, patients do not respond to dapsone
LINEAR IGA BULLOUS DISEASE alone. In these cases, adding low doses of prednisone (10–20 mg/
day) may result in significant improvement.
Linear IgA bullous disease (LABD) is a clinically heterogeneous
blistering disease in which direct immunofluorescence of peri- tHEraPEUtIC PrINCIPLES
lesional skin biopsies reveals linear deposition of IgA at the
basement membrane zone. The majority of patients with LABD Treatment of Autoimmune Blistering Diseases
presents with pruritic vesicles and papules, localized primarily Systemic corticosteroids are the initial mainstay of treatment.
to the extensor surfaces, similar to the clinical pattern seen in Dapsone is the mainstay of therapy for linear immunoglobulin A (IgA)
patients with dermatitis herpetiformis (DH). Patients with LABD dermatosis and dermatitis herpetiformis.
do not, however, have associated gluten-sensitive enteropathy, Steroid-sparing agents, including azathioprine, mycophenolate mofetil,
their disease is not improved on a gluten-free diet, and they do methotrexate, and intravenous immunoglobulin (IVIG), are often needed
not have the characteristic HLA associations of patients with DH. for treatment.
Other patients with linear IgA deposits present a clinical picture Rituximab and other anti-CD20 biologics have been proven to be very
effective as steroid-sparing agents in clinical studies.
more suggestive of BP, with pruritic tense blisters on an
erythematous base. Other clinical presentations have been
described, with clinical, histological, and immunopathological DERMATITIS HERPETIFORMIS
overlap among patients with LABD, MMP, and EBA. Children
can develop a subepidermal blistering disease with linear IgA Clinical Features
basement membrane deposits, a condition previously termed DH is an intensely pruritic blistering disease that typically presents
chronic bullous disease of childhood. In these juvenile cases, blisters in the second or third decade with erythematous papules and/
occur mainly in flexural surfaces, around the genitalia, and on or vesicles over extensor surfaces (Fig. 63.11). Patients often
the face, especially the perioral region. A drug-induced form of present with a broad spectrum of lesions. The severe pruritus
LABD can occur, mainly in association with vancomycin, but leads to scratching, resulting in erosions that may be the presenting
also with other medications. 49 feature. Patients can also present with urticarial plaques or, less
Histopathology of lesional skin of patients with LABD reflects commonly, frank bullae. Lesions are usually symmetrically
the clinical heterogeneity seen in these patients. Biopsy usually distributed over the extensor surfaces, especially the elbows, knees,
reveals collections of neutrophils in the dermal papillary tips in buttocks, back, and posterior hairline. Symptomatic mucous
a pattern virtually identical to DH. However, subepidermal blisters membrane lesions are rarely present. Extreme pruritus is a clinical
with eosinophils may also be seen, as in BP. hallmark of DH. Patients characteristically report severe burning
Direct immunofluorescence of perilesional skin in patients or stinging 12–24 hours before the appearance of lesions, which
with LABD reveals a linear band of IgA, almost exclusively IgA1, persists until vesicles break and crusts form. DH is generally
at the basement membrane zone. These IgA skin deposits contain considered a life-long dermatosis, although clinical remission
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both κ and λ light chains, indicating that the antibodies are can occur in as many as 12% of patients. The wide variety of
polyclonal. J chain is not present, suggesting that the IgA is clinical presentations of DH often suggests a long differential