Cutaneous mucormycosis caused by Mucor irregularis in a patient with CARD 9 deficiency

Dear Editor, Cutaneous mucormycosis is a rare disease caused by opportunistic fungi, which usually affects patients with immunosuppression. Mucor irregularis is a distinctive pathogenic fungus in the order Mucorales, which prevails in China. Unlike in common mucormycosis, it mostly involves nonimmunocompromised individuals.1 Gene deficiency of patients with cutaneous mucormycosis has never been reported to our knowledge. We report the first case of cutaneous mucormycosis caused by M. irregularis with CARD9 deficiency. A 46‐year‐old otherwise healthy woman presented with a gradually enlarging plaque on the left frontal area for 5 months (Fig. 1a). She noted a red papule appearing 5 months earlier, with occasional itch and without pain and discomfort of her eyes and head. She had undergone a resection of the skin lesion 4 months earlier with a diagnosis of eyelid tumour in the local hospital. However, the skin lesion relapsed and enlarged rapidly after the surgery. She worked as a farmer and had no clear trauma history. Dermatological examination revealed a 4 × 6‐cm well‐demarcated erythematous mass on her left frontal and periorbital area, with a 2‐cm scar on the upside of the eyebrow. Histopathological examination showed infiltration with multiple inflammatory cells (histocytes, neutrophils and multinucleated giant cells) with thin, short hyphae in the dermis (Fig. 1b). Microscopic examination of a direct scraping showed branched nonseptate hyphae (Fig. 1c), and tissue culture showed a yellowish white cotton‐like colony (Fig. 1d). The internal transcribed spacer regions of ribosomal DNA of the strain were sequenced. The sequence showed homology with type strain F3‐3‐8 in GenBank (KX349458) and was confirmed as M. irregularis. (a) A 4 × 6‐cm well‐demarcated erythematous mass on the patient's left frontal and periorbital area. (b) On haematoxylin and eosin staining (original magnification × 400), there is infiltration with multiple inflammatory cells with thin, short hyphae in the dermis. (c) Direct scraping microscopic examination, showing branched nonseptate hyphae. (d) Tissue culture, showing a yellowish white cotton‐like colony. (e) After 2 months of treatment with itraconazole and amphotericin B. (f, g) A heterozygous substitution c.692C>T and a heterozygous amino acid deletion mutation c.905_907delTCT were found. A diagnosis of cutaneous mucormycosis caused by M. irregularis was made and itraconazole 400 mg per day was given as treatment, combined with amphotericin B gradually increasing from 3 mg per day to 25 mg per day in 10 days and then maintained at 25 mg per day. After 2 months of treatment, the skin lesion of the patient improved to an extent (Fig. 1e). The patient suspended the amphotericin B infusion therapy due to persistent hypokalaemia and has continued taking itraconazole 400 mg per day until the present. We identified a heterozygous substitution c.692C>T (Fig. 1f) and a heterozygous amino acid deletion mutation c.905_907delTCT (Fig. 1g) in the CARD9 gene of the patient. Mucormycosis is an emerging fungal infection, with high morbidity and mortality, which mostly affects immunocompromised individuals. Unlike common mucormycosis, most M. irregularis infections affect immunocompetent patients, and progress chronically, seldom causing angioinvasion.2 Gene deficiency of patients with cutaneous mucormycosis has never been reported. The CARD9 gene, which is a key adaptor molecule in the downstream signalling of several C‐type lectin receptors, is an important factor in host defence against fungi. CARD9 deficiency has been reported in many fungal infections, such as deep dermatophytosis, mucocutaneous or invasive candidiasis, extrapulmonary aspergillus infection and dematiaceous fungal infections.3 However, CARD9 deficiency has never been found in mucormycosis, and the genetic aetiology remains to be elucidated. Lipid formulation of amphotericin B is the first‐line therapy for cutaneous mucormycosis, especially for immunocompromised patients. Surgical debridement could also be performed to increase survival rates. Posaconazole, itraconazole and the combination of lipid‐based amphotericin B plus caspofungin are also thought to be effective.4 For our patient we combined amphotericin B with itraconazole for treatment, which showed obvious effect. However, due to the patient's persistent hypokalaemia, which is one of the most severe adverse reactions of amphotericin B, we suspended the amphotericin B therapy. The patient has continued taking itraconazole, and is attending follow‐up visits in our department. Funding sources: none. Conflicts of interest: none to declare.