PMC9554596_01
Clinical image. (A) Skin lesions of the patient during the initial visit. (B) Skin lesions of the patient after 4 months of oral terbinafine and itraconazole treatment. (C) Skin lesions of the patient after 15 months of combination treatment with oral terbinafine, itraconazole, and ALA-PDT. (D) Skin lesions of the patient after 14 months of oral voriconazole. (E) Skin lesions of the patient after 4 months of oral posaconazole.
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The ulcer had an irregular edge, and its lower portion was covered with scab and contained pus ( Figure 1A ). After one month of combined therapy, the treatment for the lesion showed a good progress ( Figure 1B ). The patient was then administered combined oral itraconazole (400 mg daily) and terbinafine (250 mg daily) therapy for eight months ( Figure 1C ); these lesions remained unresponsive. Then, the therapeutic regimen was changed to voriconazole (400 mg daily), according to the in vitro antifungal susceptibility test results. Then, we tried topical amphotericin B with hydropathic compress and the ulcer on the abdomen relapsed. The skin lesions continued to deteriorate, nearly penetrating through the abdominal wall ( Figure 1D ). The condition of the lesion improved gradually and the ulcers healed after four months of this therapeutic regimen ( Figure 1E ).
Pathological diagnosis of deep dermatophytes. (A, B) Hematoxylin and eosin staining of the deep dermatophytes revealed pseudoepitheliomatous hyperplasia; neutrophilic microabscesses, epithelioid cells, and multinucleated giant cells were observed within the dermis (Magnification: A, 40x; B, 400x). (C) Periodic acid-Schiff stains showed septate fungal hyphae (black arrow) in the stratum corneum or within giant cells (Magnification: 400x).
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Neutrophilic microabscesses, epithelioid cells, and multinucleated giant cells were observed within the dermis ( Figures 2A, B ). Periodic acid-Schiff stains showed septate fungal hyphae in the stratum corneum or within giant cells ( Figure 2C ).
Results of etiological examination. (A) Direct fluorescence of multiple skin lesions were positive for pseudohyphae (Magnification: 40x). (B) Macroscopic appearance of T. tonsurans: white, villiform colony on SDA after 7 d of incubation at 28 C. (C) Microscopic examination of the morphology of mycelium.
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Direct microscopic examination of both the brown patch and the ulcer were positive for the fungal hyphae ( Figure 3A ), and tissue culture isolated a white, villiform colony on Sabouraud Dextrose Agar after seven days of incubation at 28 C ( Figure 3B ). Microscopic examination of the culture revealed hyphae with membranes and lateral interval growth of rod-shaped conidium ( Figure 3C ).
Results of immunological examination. (A) Sanger sequencing of CARD9 exon 4 reveals the heterozygous replacement of c.596A>R (red frame); F, forward chain; R, reverse chain. (B) Western blot of PBMCs showed decreased CARD9 levels, compared to healthy control; HC1, HC2, HC3, healthy control (C) Comparison of IL-1beta, IL-6, and IL-17A production between the patient and healthy control after stimulation with heat-killed isolates of patient strain (C4) and T. tonsurans wild-type strain (CMC), *P < 0.05, differences between groups were analyzed using Mann-Whitney U test. P-values reported in the study were based on a two-sided test.
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Exon 4 showed a novel c.596A>R (K196E) mutation ( Figure 4A ). Western blot of peripheral blood mononuclear cells (PBMCs) isolated from the patient showed decreased CARD9 levels, compared to that in healthy controls ( Figure 4B ). IL-6, IL-1beta and IL-17A levels were distinctly lower after stimulation, compared that in healthy controls ( Figure 4C ).