PMC6598597_01
(A-D) Clinical manifestations of the patient during clinical observational period. (A) Initially pemphigus foliaceus with involvement of the seborrheic skin areas and ptosis in myasthenia gravis, (B) lichenoid eruption at the time of thymoma recurrence, (C) erythroderma with lichenoid eruption right after thymectomy, and (D) resolution of the lichenoid eruption.
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F1
Physical examination revealed erythematous plaques with shallow erosions and overwhelming yellow-to-brown crusts, involving the trunk, mainly back, upper and, to lesser extent, lower limbs, dorsal aspect of hands, face, and scalp (Figure 1A). Several months later, she developed diffuse erythroderma (Figure 1B). Erythematous targetoid plaques, resembling erythema multiforme (EM), and hyperkeratotic plaques appeared at her lower limbs and soles, respectively (Figure 1B). After tumor resection, erythroderma with multiform lesions gradually regressed (Figure 1C) and eventually disappeared (Figure 1D). Due to the strong immunosuppressive therapy, it was impossible to systematically study peripheral blood T cell responses against distinct cutaneous autoantigens (Supplementary Figure 1).
Immune serological characteristics of the patient, (A) direct immunofluorescence (DIF) at time of pemphigus foliaceus, which showed IgG and C3 deposits at the surface of epidermal keratinocytes and (B) DIF at time of GVHD-like dermatitis which showed IgG C3 deposits along the BMZ. (C) positive DIF controls of perilesional BP skin, showing linear deposition of IgG along the BMZ (above), and positive DIF from perilesional PV skin presenting deposits at the surface of epidermal keratinocytes.
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F2
Initially, after surgical removal of the thymoma, direct immunofluorescence (DIF) from perilesional biopsy of the scaly erythematous skin rash revealed deposits of both IgG and C3 on the surface of epidermal keratinocytes (Figures 2A,C). IgG and C3 along the dermal-epidermal basement membrane zone (BMZ) (Figures 2B,C).
(A) Immunohistochemical analysis of T cell subsets in pemphigus foliaceus (PF) and lichenoid skin lesions during the observational period. (A) CD3+/Tbet+ and CD4+/GATA3+ T cell skin infiltrate in PF, the lichenoid eruption at thymoma recurrence, and after thymectomy. (B) Percentage of CD4+/GATA3+, T-Bet+, IL17A+, and FoxP3+ T cells in PF skin lesions, at thymoma recurrence and after thymectomy, (C) expression pattern of FoxP3+ T cells in adult thymus, indolent thymoma, and in PAMS-associated thymoma (present case).
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F3
A skin biopsy from the erythrodermic skin revealed liquefactive degeneration and apoptotic keratinocytes and a band-like lymphocytic infiltrate along the BMZ (Figure 3A). A third skin biopsy revealed findings consistent with GVHD-like erythroderma (Figure 3A). Th2 cells than CD3+T-Bet+ compared to the Th1-dominated GVHD-like skin lesions which inversely showed a stronger presence of CD3+T-Bet+ Th1 cells than CD4+GATA-3+ Th2 cells (Figures 3A,B). The numbers of IL-17+ T cells and of FoxP3+ Treg cells were not different between PF and GVHD-like skin lesions (Figure 3B). Moreover, the number of FoxP3+ Treg cells in the patient's thymoma at the time of recurrence was significantly lower compared to adult persistent thymus and indolent thymoma without associated autoimmune syndromes (Figure 3C).