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If at first you don't succeed: A difficult case of Linear IgA

  • Author(s): Krejci-Mawaring MD, Jennifer
  • West, MD, Daniel A
  • Tonkovic-Capin, MD, Viseslav
  • et al.
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If at first you don't succeed: A difficult case of Linear IgA
Jennifer Krejci-Manwaring MD1, Daniel A West MD2, Viseslav Tonkovic-Capin MD2
Dermatology Online Journal 15 (9): 16

1. University of Texas Health Science Center San Antonio, San Antonio, Texas
2. University of Kansas Medical Center, Division of Dermatology, Kansas City, Kansas


Abstract

We present a patient with Linear IgA who was both difficult to diagnose and treat. Numerous biopsies were needed before a positive result could be returned. Trials of multiple systemic agents failed. Eventually, a second trial of dapsone was successful and well-tolerated. The case exemplifies the determination and perseverance that is often required by both patient and physician in pursuit of symptom relief.



Introduction

Linear IgA bullous dermatosis (LABD) is a vesiculobullous skin disorder caused by circulating autoreactive immunoglobulins. In children, lesions tend to favor flexural areas; the disease usually remits in two to four years. In adults, the clinical presentation varies, and the course is less predictable [1]. Diagnosis of LABD requires clinical suspicion and corresponding skin biopsy. Classic lesions of LABD demonstrate subepidermal separation with neutrophils along the dermoepidermal junction (DEJ) or in the dermis with or without eosinophils. Direct immunofluorescence (DIF) reveals linear deposits of IgA and occasionally IgG [2]. First-line treatment is either dapsone or sulfapyridine and may require prednisone.


Case presentation

A 42-year-old Caucasian female initially sought treatment with her primary care physician for blisters on her groin, breasts, and face. She received three courses of topical and systemic antibiotics for impetigo. Lesions persisted; she was then diagnosed with herpes zoster and given valacyclovir. Upon referral to a dermatologist, a biopsy displayed a subepidermal bulla with eosinophils on H&E, but DIF and Gram stain were negative. The diagnosis was elusive, but topical therapy for a bullous dermatosis was initiated with hydrocortisone and clobetasol ointment. There was no improvement until she began prednisone 40 mg daily, which caused significant weight gain.

A third and fourth biopsy demonstrated a subepidermal split, this time with numerous neutrophils and occasional eosinophils. Again, DIF was negative. Dapsone 25 mg and cimetidine 300 mg twice daily were implemented empirically and resulted in improvement, however, the patient experienced intolerable headaches and dysphoria, so both were discontinued after two months.


Figure 1
Figure 1. Grouped, annular papulovesicles with central crusting on the face

After one year, she presented to our institution. On exam she had crusted erosions and a few scattered, tense bulla on a background of post-inflammatory hyperpigmentation in the inguinal, axillary, and inframammary areas. There was a lesser degree of involvement of the neck and face (Fig. 1). Prior to onset, she was otherwise healthy and did not take any medications, including over-the-counter medications and supplements.


Figure 2Figure 3
Figures 2-4. Sections with magnification of 4, 10, and 20. The biopsies show subepidermal blistering with extensive neutrophil involvement. (H&E)

Figure 4

We performed a biopsy (Figs. 2-4) for DIF and ordered indirect immunofluorescence (IIF). While awaiting results, we treated her with permethrin 5 percent cream to cover bullous scabies and fluconazole 200 mg once weekly for two doses for possible bullous tinea. Ultimately, DIF revealed linear deposits of IgA at the DEJ, IIF was negative, and a definitive diagnosis of LABD was made.

Because of her unpleasant experience with dapsone, we opted to treat with tetracycline 500 mg and niacinamide 500 mg three times daily in addition to prednisone and topical therapy. She improved only partially, reporting hair loss and more weight gain. We discontinued tetracycline and niacinamide and started sulfapyridine 250 mg four times daily. She showed improvement with this regimen, but flared when prednisone was lowered below 30 mg. We stopped sulfapyridine and started mycophenolate mofetil. Despite doses of up to 2 g daily, she was unable to taper off prednisone.

Because LABD is sometimes associated with underlying malignancy [3], we elected to perform computed tomography of the head, chest, abdomen, and pelvis. All studies were negative. There are rare reports of gluten-sensitive LABD [4], but strict adherence to a gluten-free diet did not change her symptoms.

After much frustration we discussed reverting back to dapsone, and she agreed to a second trial. She persevered through six weeks of headaches and dysphoria, but these side effects finally abated. Her disease continued to clear, even during the prednisone taper. Her disease has now been stable for more than one year on dapsone.


Discussion

This was a difficult case of LABD that exemplifies the adage, "If at first you don't succeed: try, try, try again." It also underlines the importance of keeping an open mind when considering different diagnoses. Four physicians, five biopsies, and three labs were required to make the diagnosis. Numerous treatments failed, but in the end, persistence paid off and the patient had relief.

References

1. Wojnarowska F, Marsden RA, Bhogal B, Black MM. Chronic bullous disease of childhood, childhood cicatricial pemphigoid and linear IgA disease of adults: A comparative study demonstrating clinical and immunopathologic overlap. J Am Acad Dermatol. 1988 Nov;19(5 Pt 1):792-805. [PubMed]

2. Nie Z, Nagata Y, Joubeh S, Hirako Y, Owaribe K, Kitajima Y, Hashimoto T. IgA antibodies of linear IgA bullous dermatosis recognize the 15th collagenous domain of BP180. J Invest Dermatol. 2000 Dec;115(6):1164-6. [PubMed]

3. Lai-Cheong JE, Groves RW, Banerjee P. Linear IgA bullous dermatosis associated with adenocarcinoma of the ascending colon. J Eur Acad Dermatol Venereol. 2007 Aug;21(7):978-9. [PubMed]

4. Egan CA, Smith EP, Taylor TB, Meyer LJ, Samowitz WS, Zone JJ. Linear IgA bullous dermatosis responsive to a gluten-free diet. Am J Gastroenterol. 2001 Jun;96(6):1927-9. [PubMed]

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