Zosteriform zygomycosis

Journal of the AmericanAcademyof Dermatology

Woods and Elewski

Volume32,Number2, Part 2

357

12. BorradoriL, SaadaV, RybojadM, et al. Oral intraepider-

21. IwatsukiK, ImaizumiS,TakagiM, et al. IntercellularIgA

ma1IgA pustulosis and Crohn’sdisease. Br J Dermatol 1992;126:383-6. 13. Wallach D, JanssenF, Vignon-Pennamen M-D, et al. Atypical neutrophilicdermatosis with subcorneal IgA deposits.Arch Dermatol1987;123:790-5. 14. Stolz W, BieberT, Meurer M. Is the atypicalneutrophilic dermatosis with subcorneal IgA deposits a variant of pemphigusfoliaceus?Br J Dermatol1989;121:276-9. 15. Wallach D, CottenotF, PelboisG, et al. Subcornealpustular dermatosisand monoclonalIgA. Br J Dermatol 1982;107:229-34. 16. NishikawaT, ShimizuH, HashimotoT. Roleof IgA intercellularantibodies: reportof clinicallyandimmunopathologicallyatypical cases.In: OrfanosCE, StadlerR, Gollnick H, eds.Proceedings of the XVII World Congress of Dermatology.Berlin: Springer-Verlag,1987:383. 17. TagamiH, IwatsukiK, IwaseY, et al. Subcornealpustular dermatosis with vesiculo-bullous eruption.Demonstration of subcorneal IgA deposits anda leukocytechemotactic factor. Br J Dermatol1983;109:581-7. 18. ProstC, Intrator L, WechslerJ, et al. IgA autoantibodies bindto pemphigus vulgarisantigenin a caseof intraepiderma1neutrophilicIgA dermatosis. J AM ACADDERMATOL

depositionin patientswith clinicalfeaturesof subcorneal pustulardermatosis. Br J Dermatol1988;119:545-7. 22. BernardP,Amici JM, BedaneC, et al. Dermatose neutrophiliquea IgA intra-kpidermique asso&ea un myklomea IgA. Ann DermatolVenereal1990;117:890-2. 23. ZillikensD, Miller K, HartmannAA, et al. IgA pempbigusfoliaceus: acasereport.Dermatologica 1990;181:304-7. 24. ChorzelskiTP, BeutnerEH, KowalewskiC, et al. IgA pemphigus foliaceuswith a cl&Cal presentationof pemphigusherpetiformis.JAMAcADD~~~~~0~1991;24:83944. 25. Koulu L, KusumiA, SteinbergMS, et al. Human autoantibodies againsta desmosomal coreproteinin pemphigusfoliaceus.J Exp Med 1984;160:1509-18. 26. Rappersberger K, RoosN, StanleyJR. Immunomorphclogicandbiochemical identificationof the pemphigus foliaceusautoantigenwithin desmosomes. J InvestDermatol 1992;99:323-30. 27. BuxtonRS, CowinP, FrankeWW, et al. Nomenclature of the desmosomal cadherins.J Cell Biol 1993;121:481-3. 28. Koch PJ, GoldschmidtMD, WalshMJ, et al. Complete aminoacidsequence of the epidermaldesmoglein precursorpolypeptideandidentificationof a secondtype of desmogleingene.Eur J Cell Biol 1991;55:200-8. 29. NeumannE, Dmochowski M, BowszycJ, et al.The occurrenceof IgA pemphigus foliaceuswithout neutiophilicinfiltration. Clin Exp Dermatol199+19:56-X.

1991;25:846-8.

19. BurrowsB, BinghamEA. Subcorneal pustulardermatosis andIgA gammopathy.Br J Dermatol1984;lll (suppl26): 91-3. 20. Todd DJ, BinghamEA, WalshM, et al. S&cornea1pustular dermatosis andIgA paraproteinemia: response to both etretinateandPUVA. Br J Dermatol1991;125:387-9.

Zosteriform zygomycosis Susan G. Woods, MD, and Boni E. Elewski, MD Cleveland,

Ohio

We describe a patient with zygomycosis that resembled herpes zoster infection. The diagnosis was readily made with a potassium hydroxide preparation that revealed sparsely to nonseptate hyphae. The patient responded to combination antifungal therapy with amphotericin B and fluconazole. The clinical response correlated with antifungal susceptibility test results. (J AM ACADDERMATOL 1995;32:357-61.) Zygomycosis is an opportunistic fungal infection in patients with specific predisposing conditions such as diabetes, malnutrition, and immunosuppression. A review of the literature since 1985 revealed that 28

cases of primary cutaneous zygomycosis have been reported in the United States. The clinical features included necrotic lesions, cellulitis, and ulceration. We describe a liver transplant recipient with cutaneous zygomycosis that resembled herpes zoster.

From the Department of Dermatology, University Hospitals of Cleveland, Case Western Reserve University. Reprint requests: Susan G. Woods, MD, University Hospitals of Cleveland, Department of Dermatology, Lakeside 3,2078 Abington Rd., Cleveland, Ohio 44106. Copyright @ 1995 by the American Academy of Dermatology, Inc. 0190-9622/95 $3.00 + 0 16,‘4,‘56466

CASE REPORT A 37-year-old woman underwent liver transplantation for sclerosingcholangitis.After transplantation, pustules

developed on her abdomen near a surgical drain site. The pustules rapidly spread in a zosteriform pattern acrossthe left sideof the abdomento the middle of the back and was

358

Journal of the American Academy of Dermatology February 1995

Woods and Elewski

Fig. 1. Clinical examination reveals a broad erythematous plaque studded with pustules, necrosis, and ulceration in a dermatomal distribution on lower portion of the abdomen.

associated with intense pain. The preliminary diagnosis was herpes zoster, but the patient did not respond to intravenously administered acyclovir. Skin examination revealed a broad, erythematous plaque studded with pustules, necrotic areas, and ulcer-

Shortly after the addition of fluconazole, 200 mg/day, to the treatment regimen, clinical improvement was noted. After 6 months of amphotericin B and fluconazole therapy, there was significant resolution of the lesions. However, later skin biopsy specimens showed persistent

ations in a dermatomal distribution on the lower portion

fungal granulomas, and these areas were excised. Use of

of the abdomen (Fig. 1). Results of a Tzanck preparation, viral cultures, and varicella zoster antibody titer were negative. A potassium hydroxide preparation revealed nonseptate hyphae. A biopsy specimen revealed a suppurative granulomatous infiltrate in the dermis with histiocytes, lympocytes, and a fungal organism (Fig. 2). Tissue culture grew an organism identified as Rhizopus arrhizus. Computed tomography of the abdomen and pelvis showed cellulitis of the soft tissues of the left lower quadrant with no evidence of intraabdominal extension. The patient wastreated with intravenous amphotericin B, 60 mg/day, and topical amphotericin B lotion three times a day. After 3 months of therapy there was only moderate improvement; therefore antifungal susceptibility testing was performed (Dr. Michael Rinaldi, University of Texas Health Science Center). This revealed susceptibility to amphotericin B (minimal inhibitory concentration [MIC] < 0.14 pg/ml) and resistance to fluconazole and itraconazole (MIC > 80 bgg/ml; MIC > 10 pg/ml). Synergy studies with amphotericin B and fluconazole demonstrated atavism (MIC < 0.14 + < 1.25 pg/ml); therefore the patient was given both fluconazole and amphotericin B.

amphotericin B was discontinued after surgery. The patient received a total dose of 100 gm of amphotericin B and 360 gm of fluconazole. There has been no recurrence 12 months after excision. DISCUSSION

Zygomycosis (mucormycosis) is an acute, often fatal opportunistic infection caused by fungi from the phylum Zygomycota, usually of the genera Absidia, Rhizotnucor, or Rhizopus.’ These organisms are ubiquitous saprophytic molds found in decaying matter and soil.2 The agents of zygomycosis cause infections in patients who are predisposed by disorders such as diabetic ketoacidosis,leukemia, lymphoma, burns, drug-induced immunosuppression, and malnutrition.3

The major types of infection can be classified into rhinocerebral, pulmonary, gastrointestinal, primary cutaneous, and disseminated.3>4

five categories:

Primary

cutaneous zygomycosis is the least com-

Journal of the American Academy of Dermatology Volume 32, Number 2, Part 2

Woods and Elewski

359

Fig. 2. Skin biopsyspecimentakenfrom abdomen.Hematoxylin-eosinstainrevealsa sup-

purative granulomatousinfiltrate in the dermiswith a fungal organismmarked by CLYTOW.

mon fortn5 By 1971 Baker6 reported that only 8 of 255 casesof zygomycosiswere of the primary cutaneous form. In the late 1970s there was an outbreak of cutaneous zygomycosisthat was attributed to the useof elastic bandages.7-13A review of the literature since 1985 revealed that 28 casesof primary cutaneouszygomycosishave been reported in the United States.Of these cases,25% of the patients were immunocompromised and 39% involved trauma. Primary cutaneous zygomycosisusually results from traumatic inoculation (intravenous injection site, catheters), burns, or from the application of contaminated materials. l4 In the casesof primary cutaneous zygomycosisassociatedwith elastic bandages, Rhizopus rhizopodiformis and Rhizopus oryzae were the cause,and R. rhizopodiformis was recovered from culture of a swab from the tape.13 The clinical lesions of cutaneous zygomycosisare typically necrotic, but cellulitis and ulceration may also occur.15,l6 Our case was unusual because the patient had minimal necrosisand a predominance of granulation tissueand inflammatiqn. The necrosisis caused by the organism’s invasion of blood vessel walls that leads to infarction. l7 Other fungi that are angioinvasive and can produce a diseaseresembling zygomycosisinclude the Aspergillus species.‘* The differential diagnosis includes ecthyma gan-

grenosum, staphylococcal cellulitis, cutaneous aspergillosis,vasculitis, and pyoderma gangrenosum.l9 The diagnosis of cutaneous zygomycosis can readily be made from a potassium hydroxide preparation showing sparselyto nonseptate,thick-walled hyphae with right-angle branching. l7 These hyphae can also be seen in hematoxylin-eosin-stained sections. The hyphae also stain with periodic acidSchiff and Gomori’s methenamine silver.‘*>2oThe diagnosis is made lessfrequently by fungal culture becausethe organism may be difficult to grow from tissue.21 The treatment of zygomycosisincludes antifungal agents, surgical debridement, and control of the underlying risk factors or disease.3The organisms of zygomycosisare usually recalcitrant to most antifungal treatment. Intravenous amphotericin B is the only agent currently recommended.22The antifungal agents most recently available (5-fluorocytosine, the imidazoles,and triazoles) have little consistentin vitro or in vivo activity against zygomycetes and have no current indication for monotherapy of zygomycosis.22-24 The optimal duration and total amount of amphotericin B that should be given for zygomycosis are unknown, thus therapy should be individualized according to the patient’s clinical response and the

360 Woods and Elewski rate of clearing of the infection.25 In most studies,a total dose of 2 gm has been administered, although some patients may need up to 4 gm.4>25-27 Several investigators have shown in vitro additive to synergistic antifungal activity when amphotericin B (a polyene) is combined with triazole antifungal drugs in murine candidiasis.28However, there are essentially no in vitro studies supporting combination antifungal treatment of zygomycosis.In our patient there was a correlation between the in vivo outcome and the in vitro results. The patient’s condition improved more with combined amphotericin B and fluconazole therapy than with amphotericin B therapy alone. The clinical improvement was noted shortly after the introduction of fluconazole, suggesting that the addition of fluconazole was important. We hypothesize that amphotericin B binds to the fungus cell wall to destabilizethis membrane and thereby allows better uptake of fluconazole into the organism. When fluconazole is internalized, it can inhibit the cytochrome P-450 system and prevent ergosterol synthesis and cytochrome respiration needed for repair of the fungal cell wall. There are reports of cure among several patients with cutaneous zygomycosisafter surgical excision alone.2gl3oThe authors of these reports emphasize the importance of early and, if necessary,repeated surgical treatment. These patients usually had early diagnoses and had a localized infection. Most patients have more widespread infection; thus surgery should be combined with amphotericin B therapy.3 In our patient surgery could not be done before antifungal treatment becausethe area of affected skin was too extensive. The control of underlying disorders is also important, especially in a diabetic patient.4$31Serum from patients with diabetic ketoacidosis lack the inhibitory activity against R arrhizus found in normal serum. This inhibitory activity was restored after correction of the acidosis.32 As in all forms of zygomycosis,the primary cutaneous variety can disseminate and cause death.18 However, the prognosis of all forms of zygomycosis has improved in recent years with a 73% survival rate among casesdiagnosed since 1970 compared with a 6% survival rate before 1970.33The improved prognosis can be attributed to earlier diagnosis that leads to aggressive surgical debridement and amphotericin B administration. A high index of suspicion for zygomycosis is needed in immunocompromised patients because

Journal of the American Academy of Dermatology February 1995

the clinical presentation may be atypical as in our patient. REFERENCES

1. RipponJW. Medical mycology:the pathogenicfungi and the pathogenicactinomycetes. 3rd ed. Philadelphia:WB Saunders,1988:681-713. 2. PrevooRLMA, Starink TM, de HaanP.Primary cutaneousmucormycosis in a healthy young girl. J AM ACAD DERMATOL1991;24:882-5. Lehrer RI. Mucormycosis.Ann Intern Med 1980;93:93107. Mayer RD, ArmstrongD. Mucormycosis-changingstatus.CRC Crit Rev Clin Lab Sci 1973;4:412-51. Umbert IJ, DanielSu WD. Cutaneousmucormycosis. J AM ACADDERMATOL1989;21:1232-4. BakerRD. The epidemiology of mucormycoses. In: Yousef AD, ed. The epidemiologyof human mycotic disease. Springfield,IlI CharlesC Thomas,1975:197-204. 7. Follow-upon Rhizopus infectionassociated with Elastoplast bandages.United States.MMWR Morb Mortal Wkly Rep 1978;27:243-4. 8. Nosocomialoutbreaksof Rhizopus infectionsassociated with Elastoplastwounddressings: Minnesota.MMWR Morb Mortal Wkly Rep 1978;27:33-4. 9. GartenbergG, BottoneEJ, KeuschGT, et al. Hospital-acquiredmucormycosis. (Rhizopus rhizopodijbrmis) of skin and subcutaneous tissue:epidemiology,mycology, and treatment.N Engl J Med 1978;299:115-8. 10. Everett ED, PearsonS, RogersW. Rhizopus surgical woundinfectionassociated with elasticizedadhesivetape dressings. Arch Surg 1979;114:738-9. 11. HammondDE, WinkehnannRK. Cutaneous phycomycosis.Reportof threecaseswith identificationof Rhizopus. Arch Dermatol1979;115:990-2. 12. Mead JH, Lupton GP, Dillavou CL, et al. Cutaneous Rhizopus infectionoccurrenceasa postoperative complication associated with an elasticizedadhesivedressing. JAMA 1979;242:272-4. 13. DennisJE, RhodesKH, CooneyDR, et al. Nosocomial Rhizopus infection(zygomycosis)in Children,J Pediatr 1980;96:824-8. 14. Radentz WH, ElewskiBE. Opportunisticmycoses.In: ElewskiBE, ed. Cutaneous fungal infection.1sted. New York: Igaku-ShoinMedical Publishers,1992184-211. 15. RadentzWH. Opportunisticfungalinfectionsin immunocompromisedhosts.J AhlAc~~D~~~~~0~1989;20:9891003. 16. BatemanCP, UmlandET, BeckerLE. Cutaneouszygomycosisin a patientwith lymphoma.J AM ACADDERMATOL 1983;8:890-4. 17. Rinaldi MG. Zygomycosis.Infect Dis Clin North Am 1989;3:19-41. 18. WilsonCB, Siber GR, O’Brien TF, et al. Phycomycotic gangrenous cellulitis-a reportof two cases anda reviewof the literature.Arch Surg 1976;111:532-7. 19. Hall JC, Brewer JH, Reed WA, et al. Cutaneousmucormycosisin a heart transplantpatient. Cutis 1988; 42183-6. 20. BakerRD. Pulmonarymucormycosis. Am J Path011956; 32:287-313. 21. RobertsSO,Hay RJ, MacKenzieDR. A clinician’sguide to fungal disease.Infectiousdiseases and antimicrobial agents.New York Marcel DekkerInc, 1984;~015.

Journal of the American Academy of Dermatology Volume 32, Number 2, Part 2

Matsuoka

22. Hammer GS, Bottone EJ, Hirschman SZ. Mucormycosis in a transplant recipient. Am J Clin Path011975;64:389-98. 23. Bennett JE. Chemotherapy of systemic mycosis. N Engl J Med 1974;290:30-2. 24. Stevens DA. Miconazole in the treatment of systemic fungal infections. Am Rev Respir Dis 1977;116:801-6. 25. Abramson E, Wilson D, Arky RA. Rhinocerebral phycomycosis in association with diabetic detoacidosis. Report of two cases and a review of clinical and experimental experience with amphotericin B therapy. Ann Intern Med 1967;66:735-42. 26. Battock DJ, Grausz H, Bobrowsky M, et al. Alternate-day amphotericin B therapy in the treatment of rhinocerebral phycomycosis (mucormycosis). Ann Intern Med 1968; 68:122-37. 27. Pillsbury HC, Fischer ND. Rhinocerebral mucormycosis. Arch Otolaryngol 1977;103:600-4. 28. Sugar AM. Interactions of amphotericin B and SCH 39304

in the treatment of experimental murine candidiasis: lack of antagonism of a polyene-azole combination. Antimicrob Agents Chemother 1991;35:1669-71. 29. Bruck HM, Nash G, Foley FD, et al. Opportunistic fungal infection in the burn wound with phycomycetes and Aspergillus. A clinical-pathologic review. Arch Surg 1971; 102:476-80. 30. ThomfordJW, WhittleseyD, EllnerJJ, et al. Invasiveprimary cutaneous phycomycosis in diabeticlegulcers.Arch Surg 1980;115:770-1. 31. BakerRD. Mucormycosis-a newdisease. JAMA 1957; 163:805-g. 32. GaleGR, WelchAM. Studieson opportunisticfungi. Inhibitionof Rhizopus oryzae by humanserum.Am J Mcd

Sci 1961;241:604-12. 33. Parfrey NA. Improveddiagnosisand prognosisof mucormycosis. A clinicopathologic studyof 33cases. Medicine 1986;65:113-23.

Neoplastic erythema nodosum Lois Y. Matsuoka,

MD Philadelphia,

Pennsylvania

We performed immunohistologicstudieson a 75-year-old white woman with erythema nodosum(EN) and a systemic lymphoma. A skin biopsy specimen from an EN lesion showed

lobular and septal pannicular infiltration by atypical lymphocytes. The cutaneous lymphocytic infiltrate wascomposed of a monoclonal population of B cells with X light chains. Atypical lymphocytes were alsoseenin the peripheral blood, and flow cytometry showeda pre-

dominance of the same phenotype of B cells with X light chains. Chemotherapy for systemic B-cell lymphoma resulted in the simultaneous resolution of EN and the lymphoma. This is the first documentation of EN representing direct cutaneous invasion by a B-cell lymphoma. (J AM ACAD DERMATOL1995;32:361-3.) Erythema nodosum (EN) is rarely associated with an internal malignancy.‘-11 Of these, the most common is a lymphoma, although the EN lesions demonstrate a characteristic septal lymphohistiocytic infiltrate similar to nonmalignant EN. 1-l 1 This article describes a patient with EN whose cutaneous lymphocytic infiltration was produced by atypical B lymphocytes of the X light chain type. Further investigations revealed a systemic lymphoma, and in addition, abundant atypical B lymphocytes with X light chains in peripheral blood. From the Department of Dermatology, Thomas Jefferson University. Repriit requests: Lois Y. Matsuoka, 211 South 9th St., PhiladeIphia, Copyright

Jefferson

MD, Department PA 19107.

@ 1995 by the American Academy 0190-9622/95 $3.00 + 0 16/4/57558

Medical

College,

of Dermatology,

of Dermatology,

CASE REPORT

A 75-year-old white woman had recurrent tender erythematous nodules of the lower legs for 8 months. She also had progressive fatigue and a weight loss of 8 pounds. According to the patient, hematologic tests and a bone marrow biopsy had been performed previously but the results (unavailable) had been “inconclusive.” Examination showed lesions typical of EN in the pretibial areas. Results of laboratory investigations were as follows: hemoglobin, 11.7 gm/dl; hematocrit, 34.7%; platelets, 12 1,000/mm3; white blood cell count, 9500/ mm3 with a differential of 13% neutrophils, 5% bands, 8 1% lymphocytes with 36% atypical forms, and 1% monocytes. Serum protein electrophoresis demonstrated a monoclonal peak in the y region. Computed tomographic scan of the abdomen showed splenomegaly and enlargedintraabdominal lymph nodes.

Inc.

A biopsy specimen of a skin nodule showed a septal and lobular panniculitis. The cellular infiltrate consisted of 361