Dermatology Online Journal

Cutaneous small-vessel vasculitis with unexpected circulating and in situ bound pemphigus autoantibodies
Miloš D Pavlović MD, and Radoš D Zečević MD
Dermatology Online Journal 11 (3): 19

Department of Dermatology, Military Medical Academy, Belgrade, Serbia & Montenegro. mdpavlovic2004@yahoo.com

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Abstract

Pemphigus or pemphigus-related autoantibodies have been found in sera of patients with diverse diseases, such as toxic epidermal necrolysis, thermal burns, and penicillin reactions. Here we report a patient with a typical cutaneous necrotizing vasculitis in whom immunofluorescence studies revealed the presence of circulating and tissue-bound pemphigus autoantibodies.

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Clinical synopsis

History

A 53-year-old woman was referred to our Department for recurrent palpable purpura and cutaneous ulcers over her lower legs. Her disease started 3 years ago with erythematous papules and palpable purpuric lesions located over her lower legs including the dorsa of her feet. The lesions were intensely pruritic. They usually evolved into shallow skin ulcers, some of them preceded with a short-lived bullous phase. Lesions used to crop in the late autumn and winter, then subside in the spring leaving hyper- and hypopigmented atrophic scars. In the second year of her disease, she experienced similar lesions located on the upper back. The disease responded well to mid-potency topical steroids only to recur shortly after stopping them. Otherwise she feels healthy and denies any other health-related problems, including Raynaud phenomenon. Family history was negative for autoimmune illness, including rheumatic and blistering diseases.

Physical examination

Figure 1
Figure 1. Cutaneous changes on lower legs

On her lower legs we found several cutaneous ulcers covered with hemorrhagic crusts along with hyper- and hypopigmented atrophic scars and a few excoriated papules (Fig. 1). A multitude of hypopigmented oval atrophic scars were distributed over her upper back. The rest of physical examination including accessible mucosal surfaces and peripheral pulses was normal.

Laboratory data

Complete blood cell count with the differential, urinalysis, routine biochemical blood tests, liver and renal function tests, liver and muscle enzymes, autoantibody screen, immunoglobulins, complement, cryoglobulins, RF, syphilis serology, antiphospholipid antibodies, lupus anticoagulant, blood viscosity, serum protein electrophoresis, throat swabs, ASO titers, chest X-rays, abdominal ultrasound, gynecologic exam, and stool examination for occult blood were all negative or within a normal range. ESR was elevated at 45 mm/h. Her blood was checked up for pemphigus antibodies upon monkey esophagus and they were found in a titer of 1: 320.

Figure 2	Figure 3
Figures 2 and 3. Endothelial cell swelling, fibrinoid necrosis, neutrophil infiltration, sparse karyorrhexis, erythrocyte extravasation, and some eosinophil infiltration around vessels.

Figure 4
Figure 4. Intercellular deposits of IgG within the epidermis of the clinically uninvolved skin.

Histopathology and immunofluorescence

Biopsy was taken from a periphery of the most recent, partially ulcerated, lesion and processed for routine histopathology and direct immunofluorescence (DIF) study. Histopathology showed partly ulcerated epidermis and foci of collagen necrosis with leukocytoclastic vasculitis of the dermal blood vessels (Figs. 2, 3). Surprisingly, DIF disclosed intercellular deposits of IgG in the epidermis along with IgG, IgM, C3 and fibrinogen deposits around dermal blood vessels in her lesional skin. Only epidermal intercellular IgG deposits were found in the clinically uninvolved skin (Fig. 4).

Management

She was instructed to have a period of bed rest and to avoid cold environment. She was given a topical steroid ointment and oral pentoxiphylline (400 mg, t.i.d). A complete remission was achieved 2 weeks later.

Comment

Cutaneous small-vessel vasculitis (CSVV) refers to a group of disorders usually characterized by palpable purpura and the result of necrotizing, mostly leukocytoclastic, vasculitis of dermal postcapillary venules [1]. It is believed that the majority of cutaneous necrotizing vasculitides are a consequence of immune-complex deposition in the walls of the affected blood vessels. Yet the etiology of the disorder remains elusive in up to 60-70 percent of patients [1, 2, 3]. Pemphigus is a group of acquired autoimmune bullous dermatoses resulting from the production of autoantibodies directed to an array of epithelial adhesion molecules, which in turn result in disruption of intercellular cohesion clinically manifesting as cutaneous or mucosal bullae and erosions [4]. Pemphigus or pemphigus-related autoantibodies have been found in sera of healthy relatives of patients with this disease as well as in some other diseases, such as toxic epidermal necrolysis, thermal burns, and penicillin reactions [5, 6].

The case presented is unusual in several respects. The seasonal appearance of her vasculitic lesions was reminiscent of livedo vasculopathy but her condition lacked some common features of the disease, i.e., livedo reticularis, atrophie blanche changes, and fibrin thrombi within the superficial blood vessels [7]. Additionally, pain but not pruritus is a usual symptom in livedo vasculopathy. Several episodes of presumably vasculitic lesions over her upper back are quite unusual for livedo vasculopathy and even for CSVV [1, 7]. The cause of her vasculitis could not be found despite a thorough examination.

The incidental finding of intraepidermal intercellular deposits of IgG together with circulating pemphigus autoantibodies in a relatively high titer was surprising. Histologic examination of her lesional skin did not show any signs of acantholysis, and her history did not disclose any relatives with pemphigus. Occasional blisters she did notice surmounting some of her purpuric lesions might be a consequence of her pemphigus antibodies as well as of the vasculitic process. It may be argued that indirect immunofluorescence (IIF) testing may give many false positives at some laboratories. However, a recent study comparing serodiagnosis of pemphigus vulgaris by standard IIF testing on monkey esophagus and a commercially available enzyme-linked immunosorbent assays (ELISA) showed that, with IIF, none of 50 controls was positive [8]. In a quality control survey at our own laboratory, we did not detect a single positive IIF test among 30 tested sera of patients with other inflammatory dermatoses (unpublished data).

We believe that CSVV should be added to the list of skin conditions which might be accompanied by the appearance of pemphigus autoantibodies without overt clinical manifestations of pemphigus.

References

1. Lotti T, Ghersetich I, Comacchi C, Jorizzo JL. Cutaneous small-vessel vasculitis. J Am Acad Dermatol 1998; 39: 667-87.

2. Callen JP. A clinical approach to the vasculitis patient in the dermatologic office. Clin Dermatol 1999; 17: 549-53.

3. Chua SH, Lim JT, Ang CB. Cutaneous vasculitis seen at a skin referral centre in Singapore. Singapore Med J 1999; 40: 147-50.

4. Stanley JR. Pemphigus. In: Freedberg IM, Eisen AZ, Wolff K, Austen KF, Goldmsith LA, Katz SI, Fitzpatrick TB, editors. Dermatology in general medicine. New York: McGraw-Hill; 1999. p. 654-65.

5. Brandsen R, Frusic-Zlotkin M, Lyubimov H, Yunes F, Michel B, Tamir A, et al. Circulating pemphigus IgG in families of patients with pemphigus: Comparison of indirect immunofluorescence, direct immunofluorescence, and immunoblotting. J Am Acad Dermatol 1997; 36: 44-52.

6. Wojnarowska F, Eady RAJ, Burge SM. Bullous eruptions. In: Champion RH, Burton JL, Burns DA, Breathnach SM. Textbook of dermatology. Oxford: Blackwell Science; 1998. p.1817-98.

7. Jorizzo JL. Livedoid vasculopathy: what is it? Arch Dermatol 1998; 134: 491-3.

8. Zagorodniuk I, Weltfriend S, Shtruminger L, Sprecher E, Kogan O, Pollack S, Bergman R. A comparison of anti-desmoglein antibodies and indirect immunofluorescence in the serodiagnosis of pemphigus vulgaris. Int J Dermatol 2005; 44: 541-4.

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