Pemphigus foliaceus

Physical exam showed thickened, gray plaques on the scalp and erythematous, hyperkeratotic plaques on the cheeks, trunk, genitals, and bilateral lower extremities with excoriated papules. No intact vesicles or bullae were seen. No other mucous membranes were involved.


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Differential diagnosis included Darier’s disease and pemphigus foliaceus. A 4-mm punch biopsy showed a neutrophil-containing scale crust and areas of wedge-shaped eosinophilia of the epidermis suggesting an excoriation effect. Focally, corps ronds and grains were identified along with a sparse dermal perivascular lymphoid infiltrate. There was no suggestion of a Darier-like acantholytic process, and the stratum spinosum appeared to be intact. Direct immunofluorescence showed moderate-to-intense granular pericellular deposition that was panepidermal along keratinocyte cell membranes. Immunoglobulin (Ig)G was more abundantly present than C1q complement, which was more abundantly present than C3 complement. IgA/fibrin was negative, and IgM showed colloid bodies. Pathology confirmed that the immunofluorescence findings were consistent with a pemphigus state.

This patient was diagnosed with pemphigus foliaceus (PF), a disease that usually presents with cutaneous blistering and erosions attributable to antibodies against desmoglein 1.1 PF differs from the more common pemphigus vulgaris (PV) in that antibodies against desmoglein 3 are not usually seen, and the blister formation is more superficial than in PV. Thus, erosions are seen more than blisters.2 In PF, primary lesions are small, superficial blisters that quickly become erosions.3 Typical presentation includes scaly, crusted erosions on an erythematous base often first found on the trunk with future spread to other seborrheic areas, such as the face and scalp.3 The erosions may be accompanied by a burning sensation and local pain.3 Physical exam often shows a positive Nikolsky sign, which means that physical trauma can shear the pathologic epidermis, causing clinical lesions.3 Clinically, the Nikolsky sign can be demonstrated by twisting a pencil eraser against the skin. If positive, a blister will form in the area. Atrophic changes of the nails and hair may be seen, as can erythroderma.3 Mucous membranes are rarely involved in PF, unlike PV.3 The most common age of onset for PF is between 50 and 60 years.3 Unlike PV, PF is not seen more commonly in Jews or in people of Mediterranean descent.3 PF sometimes develops in patients with PV and, more rarely, PV has been shown to develop in patients with PF.4

PF is seen throughout the world but has an endemic form known as Fogo Selvagem (FS), which is found in high frequency in Colombia and central and southwestern Brazil.3 This form of PF shares similar clinical, histologic, and immunologic features with the nonendemic form.1 Patients with FS are typically outdoor workers, and the most common time of onset is at the end of the rainy season, suggesting that a prevalence of insects is associated with increased FS.1 Areas with high rates of FS are also found to overlap with the endemic areas of Chagas disease, leishmaniasis, and onchocerciasis, all of which are vector-borne diseases transmitted by insects.1 FS is thought to be induced by an insect-transmitted viral infection.3 PF has been seen in all races, and its prevalence among men and women is about equal.3 FS can occur at any age but is usually found in those between the ages of 20 and 30 years.3

PF can also be drug-induced, which has been best documented with penicillamine and ACE inhibitors (most commonly captopril).5 These two drugs are chemically related, both having sulfhydryl groups, and can potentially cause PF.5 Patients with drug-induced pemphigus fall into two groups: those whose symptoms are relieved after discontinuation of the drug and those who continue to have active disease even after drug withdrawal.5 Most patients with drug-induced PF have circulating auto­antibodies against the PF antigen complex.5 Symptoms that are relieved by discontinuing the drug are thought to be attributable to the ability of both penicillamine and captopril to cause acantholysis.5 This has been shown by both drugs’ ability to cause acantholysis in vitro in absence of autoantibody.5 There has been one report of lisinopril-induced PF; lisinopril is a nonsulfhydryl ACE inhibitor.6 Although our patient was on lisinopril, the timeline makes the drug a highly unlikely culprit.

The course of PF is usually chronic without treatment, although spontaneous remission may sometimes occur.3 Proper treatment involves immunosuppression using systemic glucocorticoids and/or other immunomodulatory adjuvants.2 Systemic glucocorticoids currently play a major role in treatment, but the optimal regimen is still unknown.2 Mycophenolate mofetil displays superior disease control compared with azathioprine.7 However, azathioprine and cyclophosphamide showed superior steroid-sparing capacity compared with mycophenolate.2 When treating with immunomodulatory agents, watch for such adverse side effects as thrombocytopenia, neutropenia, anemia, and potential liver and kidney damage. Immunosuppression places a patient at increased risk for infection and cancer.

In this patient, lisinopril was discontinued. We initiated prednisone 80 mg daily with taper down to a present dose of 20 mg daily plus dapsone 100 mg daily. The man’s skin is clear except for erythema and scale on the cheeks. Because of the patient’s decrease in renal function with elevated creatinine and blood urea nitrogen, we were not able to utilize azathioprine or cyclophosphamide. More research is needed to determine the optimal treatment for PF.

Mr. Weingartner is a third-year medical student at the University of Oklahoma College of Medicine in Oklahoma City. Dr. Allen, associate professor, and Ms. Hennigan work in the Department of Dermatology at the University of Oklahoma Health Sciences Center in Oklahoma City. They have no relationships to disclose relating to the content of this article.


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References

  1. Culton DA, Qian Y, Ning L, et al. Advances in pemphigus and its endemic pemphigus foliaceus (Fogo Selvagem) phenotype: a paradigm of human autoimmunity. J Autoimmun. 2008; 31:311-324.
  2. Korman NJ, Eyre RW, Zone J, Stanley JR. Drug-induced pemphigus: autoantibodies directed against the pemphigus antigen complexes are present in penicillamine and captopril-induced pemphigus. J Invest Dermatol. 1991;96:273-276.
  3. Martin LK, Agero AL, Werth V, Villanueva E, et al. Interventions for pemphigus vulgaris and pemphigus foliaceus. Cochrane Database Syst Rev. 2009;1:CD006263.
  4. Mimouni D, Anhalt GJ, Cummins DL, et al. Treatment of pemphigus vulgaris and pemphigus foliaceus with mycophenolate mofetil. Arch Dermatol. 2003;139:739-742.
  5. Park SG, Chang JY, Cho YH, et al. Transition from pemphigus foliaceus to pemphigus vulgaris: case report with literature review. Yonsei Med J. 2006;47:278-281.
  6. Patterson CRS, Davies MG. Pemphigus foliaceus: an adverse reaction to lisinopril. J Dermatolog Treat. 2004;15:60-62.
  7. Emedicine. Pemphigus foliaceus.

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