Deep cutaneous candidiasis of the lip in a patient with acute myelogenous leukemia

IntroductionMucocutaneous lesions may be the presenting sign in superficial and deep cutaneous fungal disease, presenting with various morphologies ranging from papulopustular to necrotic papules or plaques. Invasive candidiasis typically presents as disseminated acneiform-appearing papules in a patient with fevers and myalgias.1Kullberg B.J. Arendrup M.C. Invasive candidiasis.N Engl J Med. 2015; 373: 1445-1456https://doi.org/10.1056/NEJMRA1315399Crossref PubMed Scopus (0) Google Scholar,2Guarana M. Nucci M. Acute disseminated candidiasis with skin lesions: a systematic review.Clin Microbiol Infect. 2018; 24: 246-250https://doi.org/10.1016/j.cmi.2017.08.016Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar Here, we discuss a case of deep cutaneous candidiasis presenting as a single indurated necrotic plaque of the upper vermillion lip, with the clinical presentation initially more suggestive of mucormycosis.3Castrejón-Pérez A.D. Miranda I. Welsh O. Welsh E.C. Ocampo-Candiani J. Cutaneous mucormycosis.An Bras Dermatol. 2017; 92: 304-311https://doi.org/10.1590/ABD1806-4841.20176614Crossref PubMed Google ScholarCase reportA 56-year-old female with acute myeloid leukemia was admitted for induction chemotherapy with cytarabine and daunorubicin. Dermatology was consulted for an indurated purpuric ulcerating plaque of the upper vermillion lip that had been tender and enlarging for 2 weeks (Fig 1, A). On examination, the patient was also noted to have a painful angulated ulcerated plaque with a violaceous rim on her hard palate (Fig 1, B). She had no history of orolabial herpes simplex virus infection. The differential diagnosis included infiltrative leukemic involvement of skin/mucosa, lymphoma, melanoma, neutrophilic dermatosis, and invasive fungal infection.A skin biopsy of the vermillion lip was performed, with amphotericin B initiated thereafter given clinical concern for mucormycosis. A potassium hydroxide preparation performed on skin tissue showed numerous pseudohyphae and yeast forms. Dermatopathologic examination revealed deep periodic acid Schiff plus diastase + budding yeast forms suggestive of Candida species without angioinvasion (Fig 2). Tissue culture grew numerous Candida dubliniensis. Beta-d-glucan and galactomannan tests were both negative. Admission blood cultures remained negative. The patient was transitioned to voriconazole once susceptibilities returned with complete resolution over 3 months.Fig 2Dermatopathology findings of deep cutaneous candidiasis of the lip. A, Sections stained with hematoxylin and eosin demonstrate a necrotizing panniculitis (magnification ×20). B, In the deep necrotic area, periodic acid Schiff plus diastase staining reveals budding yeast forms with pseudohyphae suggestive of Candida morphology. No angioinvasion is apparent.View Large Image Figure ViewerDownload Hi-res image Download (PPT)DiscussionPrimary deep cutaneous candidiasis describes a rare phenomenon in which candida is found in deeper cutaneous structures but has not yet disseminated.4Fang S.Y. Wei K.C. Chen W.C. et al.Primary deep cutaneous candidiasis caused by Candida duobushaemulonii in a 68-year-old man: the first case report and literature review.Mycoses. 2016; 59: 818-821https://doi.org/10.1111/MYC.12540Crossref PubMed Google Scholar Invasive candidiasis comprises both candidemia and deep-seated candidiasis.1Kullberg B.J. Arendrup M.C. Invasive candidiasis.N Engl J Med. 2015; 373: 1445-1456https://doi.org/10.1056/NEJMRA1315399Crossref PubMed Scopus (0) Google Scholar Though candidemia is generally more common, deep-seated disease may arise from either direct inoculation of a sterile site or hematogenous spread.1Kullberg B.J. Arendrup M.C. Invasive candidiasis.N Engl J Med. 2015; 373: 1445-1456https://doi.org/10.1056/NEJMRA1315399Crossref PubMed Scopus (0) Google Scholar,5Salazar S.B. Simões R.S. Pedro N.A. Pinheiro M.J. Carvalho M.F.N.N. Mira N.P. An overview on conventional and non-conventional therapeutic approaches for the treatment of candidiasis and underlying resistance mechanisms in clinical strains.J Fungi (Basel). 2020; 6: 23https://doi.org/10.3390/jof6010023Crossref Scopus (21) Google Scholar Invasive candidiasis should be considered in patients with neutropenia and have unexplained fever unresponsive to antibiotics.6Mays S.R. Bogle M.A. Bodey G.P. Cutaneous fungal infections in the oncology patient: recognition and management.Am J Clin Dermatol. 2006; 7: 31-43https://doi.org/10.2165/00128071-200607010-00004Crossref PubMed Scopus (86) Google Scholar,7Pappas P.G. Lionakis M.S. Arendrup M.C. Ostrosky-Zeichner L. Kullberg B.J. Invasive candidiasis.Nat Rev Dis Primers. 2018; 4: 18026https://doi.org/10.1038/NRDP.2018.26Crossref PubMed Scopus (0) Google Scholar Ocular involvement is common in disseminated disease and should be evaluated when there is a suspicion and/or when ocular symptoms are present.7Pappas P.G. Lionakis M.S. Arendrup M.C. Ostrosky-Zeichner L. Kullberg B.J. Invasive candidiasis.Nat Rev Dis Primers. 2018; 4: 18026https://doi.org/10.1038/NRDP.2018.26Crossref PubMed Scopus (0) Google Scholar Our patient presented with a deep cutaneous infection as shown by her biopsy, and her negative blood cultures and lack of additional symptoms and organ involvement suggested her disease was not yet invasive.Diagnosing deep cutaneous candidiasis involves biopsy with tissue culture to isolate the fungal organism.1Kullberg B.J. Arendrup M.C. Invasive candidiasis.N Engl J Med. 2015; 373: 1445-1456https://doi.org/10.1056/NEJMRA1315399Crossref PubMed Scopus (0) Google Scholar,8Richardson M.D. Kokki M.H. Diagnosis and prevention of fungal infection in the immunocompromized patient.Blood Rev. 1998; 12: 241-254https://doi.org/10.1016/S0268-960X(98)90006-6Crossref PubMed Scopus (37) Google Scholar Historically, albicans species accounted for the majority of isolates. However, nonalbicans Candida species are becoming increasingly prevalent and account for about half of all isolates detected in recent surveys.1Kullberg B.J. Arendrup M.C. Invasive candidiasis.N Engl J Med. 2015; 373: 1445-1456https://doi.org/10.1056/NEJMRA1315399Crossref PubMed Scopus (0) Google Scholar,5Salazar S.B. Simões R.S. Pedro N.A. Pinheiro M.J. Carvalho M.F.N.N. Mira N.P. An overview on conventional and non-conventional therapeutic approaches for the treatment of candidiasis and underlying resistance mechanisms in clinical strains.J Fungi (Basel). 2020; 6: 23https://doi.org/10.3390/jof6010023Crossref Scopus (21) Google Scholar Our patient’s tissue culture grew C dubliniensis, a species first described in 1995 that is seen in immunocompromised hosts, is associated with fluconazole resistance, and is similar to Candida albicans.9Sullivan D.J. Westerneng T.J. Haynes K.A. Bennett D.E. Coleman D.C. Candida dubliniensis sp. nov.: phenotypic and molecular characterization of a novel species associated with oral candidosis in HIV-infected individuals.Microbiology (Reading). 1995; 141: 1507-1521https://doi.org/10.1099/13500872-141-7-1507Crossref PubMed Scopus (650) Google Scholar Candida species are generally treated with azoles though this class is not recommended as initial therapy in patients with neutropenia given possibility of azole-resistant candida species or other nonresponsive organisms.5Salazar S.B. Simões R.S. Pedro N.A. Pinheiro M.J. Carvalho M.F.N.N. Mira N.P. An overview on conventional and non-conventional therapeutic approaches for the treatment of candidiasis and underlying resistance mechanisms in clinical strains.J Fungi (Basel). 2020; 6: 23https://doi.org/10.3390/jof6010023Crossref Scopus (21) Google Scholar Instead treatment should be initiated promptly with broad-spectrum agents such as amphotericin B and narrowed if and when appropriate, such as with our patient who completed her course on voriconazole.5Salazar S.B. Simões R.S. Pedro N.A. Pinheiro M.J. Carvalho M.F.N.N. Mira N.P. An overview on conventional and non-conventional therapeutic approaches for the treatment of candidiasis and underlying resistance mechanisms in clinical strains.J Fungi (Basel). 2020; 6: 23https://doi.org/10.3390/jof6010023Crossref Scopus (21) Google ScholarHerein, we described a case of primary deep cutaneous candidiasis in a patient with neutropenia presenting as a single indurated, ulcerated plaque mimicking mucormycosis rather than the more typical diffuse erythematous papular eruption often seen in disseminated disease1Kullberg B.J. Arendrup M.C. Invasive candidiasis.N Engl J Med. 2015; 373: 1445-1456https://doi.org/10.1056/NEJMRA1315399Crossref PubMed Scopus (0) Google Scholar,2Guarana M. Nucci M. Acute disseminated candidiasis with skin lesions: a systematic review.Clin Microbiol Infect. 2018; 24: 246-250https://doi.org/10.1016/j.cmi.2017.08.016Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar or white patches seen in superficial oral disease. To the best of our knowledge, this individual represents the first case of deep cutaneous candidiasis with C dubliniensis in an oncology patient. Although there is no specific amount of time before dissemination can be expected, it is important not to delay treatment as 1-2 day delays in initiation of therapy portend increased mortality.6Mays S.R. Bogle M.A. Bodey G.P. Cutaneous fungal infections in the oncology patient: recognition and management.Am J Clin Dermatol. 2006; 7: 31-43https://doi.org/10.2165/00128071-200607010-00004Crossref PubMed Scopus (86) Google Scholar While initial antifungal treatment for the clinical presentation and morphology presented herein should still include coverage for mucormycosis molds, patients confirmed to have candidiasis alone after careful clinicopathologic correlation can be narrowed to azoles or echinocandins upon speciation. Ultimately, our patient’s cultures were susceptible to azoles, and she did well on voriconazole alone. IntroductionMucocutaneous lesions may be the presenting sign in superficial and deep cutaneous fungal disease, presenting with various morphologies ranging from papulopustular to necrotic papules or plaques. Invasive candidiasis typically presents as disseminated acneiform-appearing papules in a patient with fevers and myalgias.1Kullberg B.J. Arendrup M.C. Invasive candidiasis.N Engl J Med. 2015; 373: 1445-1456https://doi.org/10.1056/NEJMRA1315399Crossref PubMed Scopus (0) Google Scholar,2Guarana M. Nucci M. Acute disseminated candidiasis with skin lesions: a systematic review.Clin Microbiol Infect. 2018; 24: 246-250https://doi.org/10.1016/j.cmi.2017.08.016Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar Here, we discuss a case of deep cutaneous candidiasis presenting as a single indurated necrotic plaque of the upper vermillion lip, with the clinical presentation initially more suggestive of mucormycosis.3Castrejón-Pérez A.D. Miranda I. Welsh O. Welsh E.C. Ocampo-Candiani J. Cutaneous mucormycosis.An Bras Dermatol. 2017; 92: 304-311https://doi.org/10.1590/ABD1806-4841.20176614Crossref PubMed Google Scholar