case_images: PMC9583697_01
case_images: Clinical, histological, and genetic features of Case 1. (A) Pedigree of the family with HHD. Affected individuals are represented by a solid square or circle, depending upon the gender, and the proband (the present case) is indicated by an arrow. (B, C) Clinical findings at the first visit to our hospital. (D) Pathological features of the lesion on the right axilla. Hematoxylin and eosin staining (scale bars, 100 mum). (E) The patient is heterozygous for a nonsense mutation (C) c.457C > T (p. Arg153Ter) in ATP2C1. (F, G) The most severe state, at the third hospitalization. (H, I) Clinical improvement after a month of treatment with apremilast following the initial 2-week treatment with oral corticosteroid.
case_images: fgene-13-884359-g001.jpg
case_images: PMC9583697_01_fgene-13-884359-g001.jpg
case_images: F1
case_images: He had a family history of similar symptoms (Figure 1A) and had been histologically diagnosed with HHD. Physical examination revealed well-circumscribed and painful erosions and erythema on the axillae and inguinal areas (Figures 1B,C). Our histological re-evaluation showed prominent spinous layer acantholysis (Figure 1D). Arg153Ter) in ATP2C1 and the HHD diagnosis was confirmed (Figure 1E). At the third hospitalization, the lesions had spread to around 50% of the body surface area (BSA) (Figures 1F,G). He started taking 30 mg apremilast twice daily after completing a 6-days titration period, resulting in drastic improvement of the lesions within a month (Figures 1H,I).
case_images: PMC9583697_02
case_images: Clinical and histological features of Case 2. (A, B) Clinical findings at the first visit to our hospital. (C) Pathological features of the lesion on the right axilla. Hematoxylin and eosin staining (scale bars, 100 mum). (D) Gene expression levels of ATP2C1 in whole skin samples taken from HHD patients and healthy controls. Statistical significance was calculated using one-way ANOVA with multiple comparisons test. Error bars represent SD. ***p < 0.001; ns, not significant. (E, F) No improvement after three months of treatment with apremilast.
case_images: fgene-13-884359-g002.jpg
case_images: PMC9583697_02_fgene-13-884359-g002.jpg
case_images: F2
case_images: Clinically, he had painful erosions on the axillae and inguinal areas with strong odour (Figures 2A,B). Histologic findings from right axilla showed obvious acantholysis and hyperkeratosis (Figure 2C). Case 1 compared to healthy controls, suggesting other factors affecting ATP2C1 expression (Figure 2D). Considering the fact that ATP2C1 mutations have not been identified in a few HHD cases, this case was also considered to be consistent with HHD.