Vancomycin-associated neutrophilic dermatitis histologically mimicking Cryptococcus
Authors: Alan S. Boyd, Melanie Ortleb
Journal: Journal of the American Academy of Dermatology (2014)

To the Editor: Morphologic mimic of Cryptococcus in a neutrophilic dermatitis (MMCND) is a recently described entity that is virtually indistinguishable from cutaneous cryptococcal infection when routine histopathology is used.Case: A 63-year-old man with recurrent Cryptococcus difficile colitis was treated with oral vancomycin; 24 hours later, an eruption on his back with "burning" symptoms developed. This eruption spread to involve his arms and thighs. The next day, 2 tense bullae appeared on his abdomen. The patient had hemodialysis-dependent end-stage renal disease, chronic obstructive pulmonary disease, and coronary artery disease. He took numerous medications, with vancomycin being the only recent addition. His physical examination revealed edematous, erythematous papules coalescing into a plaque on his back (Fig 1), similar lesions on his chest, upper extremities, and thighs with 2 tense bullae on his abdomen. He was afebrile with a normal white blood cell count.Histopathologic evaluation demonstrated basophilic bodies with surrounding clear spaces occupying the upper reticular and papillary dermis (Fig 2). Dermal edema was also appreciated, with scattered lymphocytes, histiocytes, and neutrophils. Gomori methenamine silver and mucin stains were unremarkable. Lysozyme, CD15, and myeloperoxidase stains highlighted numerous neutrophils. A direct immunofluorescence study was negative.Fig 2Vancomycin-associated neutrophilic dermatitis histologically mimicking Cryptococcus. Histologic images from our patient's biopsy. Diffuse dermal inflammation with neutrophils, neutrophilic nuclear debris, and basophilic bodies with surrounding clear spaces (arrows). (Hematoxylin-eosin stain; original magnification: ×40.)View Large Image Figure ViewerDownload Hi-res image Download (PPT)The patient's vancomycin was discontinued and he was begun on oral metronidazole. Application of topical triamcinolone 0.1% cream ameliorated the symptoms, with the eruption slowly fading over the ensuing week.Comment. Ko et al1Ko J.S. Fernandez A.P. Anderson K.A. Burdick L.M. Billings S.D. Procop G.W. et al.Morphologic mimickers of Cryptococcus occurring within inflammatory infiltrates in the setting of neutrophilic dermatitis: a series of three cases highlighting clinical dilemmas associated with a novel histopathologic pitfall.J Cutan Pathol. 2013; 40: 38-45Crossref PubMed Scopus (17) Google Scholar reported three MMCND patients with acute myeloid leukemia, chronic lymphocytic leukemia/small lymphocytic lymphoma, and questionable systemic lupus erythematosus. Two had cutaneous biopsies demonstrating leukocytoclastic vasculitis early in their clinical course and failed to respond to systemic steroid therapy; eventually both died of their diseases. The authors concluded that both patients' biopsies represented Sweet syndrome or a variant thereof. The third patient was treated with topical metronidazole and experienced improvement.The clinical morphology of these lesions varies. Most consist of erythematous to dusky red papules/plaques which may develop hemorrhagic necrosis and ulceration. They were described as painful and pruritic.The most salient histologic feature of MMCND is the basophilic bodies with surrounding vacuolated spaces resembling the capsule of cryptococcal organisms. Tissue stains for fungus, however, are negative, as are stains for mucopolysaccharides. Ko et al1Ko J.S. Fernandez A.P. Anderson K.A. Burdick L.M. Billings S.D. Procop G.W. et al.Morphologic mimickers of Cryptococcus occurring within inflammatory infiltrates in the setting of neutrophilic dermatitis: a series of three cases highlighting clinical dilemmas associated with a novel histopathologic pitfall.J Cutan Pathol. 2013; 40: 38-45Crossref PubMed Scopus (17) Google Scholar employed transmission electron microscopy on affected tissue, concluding that these bodies represented degenerating cell nuclei undergoing autolysis and apoptosis. The presence in our patient of smaller debris more characteristic of the karyorrhexis associated with neutrophil nuclear destruction would support this contention.The association between vancomycin administration and linear IgA disease has been proposed.2Carpenter S. Berg D. Sidhu-Malik N. Hall 3rd, R.P. Rico M.J. Vancomycin-associated linear IgA dermatosis. A report of three cases.J Am Acad Dermatol. 1992; 26: 45-48Abstract Full Text PDF PubMed Scopus (85) Google Scholar However, an evaluation of the literature failed to disclose any described cases of vancomycin association with any of the well-recognized neutrophil-rich dermatoses including Sweet syndrome, pyoderma gangrenosum, Behçet syndrome, or periodic fever syndromes. Moreover, vancomycin administration is more commonly linked to neutropenia than an increased presence of neutrophils.3Sanche S.E. Dust W.N. Shevchuk Y.M. Vancomycin-induced neutropenia resolves after substitution with teicoplanin.Clin Infect Dis. 2000; 31: 824-825Crossref PubMed Scopus (18) Google Scholar Given the rarity of MMCND it would be speculative to hypothesize as to its etiopathogenesis. As subsequent cases are reported, hopefully greater insight on the nature of this condition can be elucidated. To the Editor: Morphologic mimic of Cryptococcus in a neutrophilic dermatitis (MMCND) is a recently described entity that is virtually indistinguishable from cutaneous cryptococcal infection when routine histopathology is used. Case: A 63-year-old man with recurrent Cryptococcus difficile colitis was treated with oral vancomycin; 24 hours later, an eruption on his back with "burning" symptoms developed. This eruption spread to involve his arms and thighs. The next day, 2 tense bullae appeared on his abdomen. The patient had hemodialysis-dependent end-stage renal disease, chronic obstructive pulmonary disease, and coronary artery disease. He took numerous medications, with vancomycin being the only recent addition. His physical examination revealed edematous, erythematous papules coalescing into a plaque on his back (Fig 1), similar lesions on his chest, upper extremities, and thighs with 2 tense bullae on his abdomen. He was afebrile with a normal white blood cell count. Histopathologic evaluation demonstrated basophilic bodies with surrounding clear spaces occupying the upper reticular and papillary dermis (Fig 2). Dermal edema was also appreciated, with scattered lymphocytes, histiocytes, and neutrophils. Gomori methenamine silver and mucin stains were unremarkable. Lysozyme, CD15, and myeloperoxidase stains highlighted numerous neutrophils. A direct immunofluorescence study was negative. The patient's vancomycin was discontinued and he was begun on oral metronidazole. Application of topical triamcinolone 0.1% cream ameliorated the symptoms, with the eruption slowly fading over the ensuing week. Comment. Ko et al1Ko J.S. Fernandez A.P. Anderson K.A. Burdick L.M. Billings S.D. Procop G.W. et al.Morphologic mimickers of Cryptococcus occurring within inflammatory infiltrates in the setting of neutrophilic dermatitis: a series of three cases highlighting clinical dilemmas associated with a novel histopathologic pitfall.J Cutan Pathol. 2013; 40: 38-45Crossref PubMed Scopus (17) Google Scholar reported three MMCND patients with acute myeloid leukemia, chronic lymphocytic leukemia/small lymphocytic lymphoma, and questionable systemic lupus erythematosus. Two had cutaneous biopsies demonstrating leukocytoclastic vasculitis early in their clinical course and failed to respond to systemic steroid therapy; eventually both died of their diseases. The authors concluded that both patients' biopsies represented Sweet syndrome or a variant thereof. The third patient was treated with topical metronidazole and experienced improvement. The clinical morphology of these lesions varies. Most consist of erythematous to dusky red papules/plaques which may develop hemorrhagic necrosis and ulceration. They were described as painful and pruritic. The most salient histologic feature of MMCND is the basophilic bodies with surrounding vacuolated spaces resembling the capsule of cryptococcal organisms. Tissue stains for fungus, however, are negative, as are stains for mucopolysaccharides. Ko et al1Ko J.S. Fernandez A.P. Anderson K.A. Burdick L.M. Billings S.D. Procop G.W. et al.Morphologic mimickers of Cryptococcus occurring within inflammatory infiltrates in the setting of neutrophilic dermatitis: a series of three cases highlighting clinical dilemmas associated with a novel histopathologic pitfall.J Cutan Pathol. 2013; 40: 38-45Crossref PubMed Scopus (17) Google Scholar employed transmission electron microscopy on affected tissue, concluding that these bodies represented degenerating cell nuclei undergoing autolysis and apoptosis. The presence in our patient of smaller debris more characteristic of the karyorrhexis associated with neutrophil nuclear destruction would support this contention. The association between vancomycin administration and linear IgA disease has been proposed.2Carpenter S. Berg D. Sidhu-Malik N. Hall 3rd, R.P. Rico M.J. Vancomycin-associated linear IgA dermatosis. A report of three cases.J Am Acad Dermatol. 1992; 26: 45-48Abstract Full Text PDF PubMed Scopus (85) Google Scholar However, an evaluation of the literature failed to disclose any described cases of vancomycin association with any of the well-recognized neutrophil-rich dermatoses including Sweet syndrome, pyoderma gangrenosum, Behçet syndrome, or periodic fever syndromes. Moreover, vancomycin administration is more commonly linked to neutropenia than an increased presence of neutrophils.3Sanche S.E. Dust W.N. Shevchuk Y.M. Vancomycin-induced neutropenia resolves after substitution with teicoplanin.Clin Infect Dis. 2000; 31: 824-825Crossref PubMed Scopus (18) Google Scholar Given the rarity of MMCND it would be speculative to hypothesize as to its etiopathogenesis. As subsequent cases are reported, hopefully greater insight on the nature of this condition can be elucidated.