PMC4357681_01
a Pedigree of the case. The present case (I-1) had had psoriasis vulgaris for 31 years and developed GPP at 78 years of age. Her brother (I-2) had psoriasis vulgaris and her daughter (II-1) had arthritis with a high titer of ANA. Her niece (II-2) had psoriatic arthritis. b Clinical course of the lesion on her right lower leg before and after GMA. Left: The patient showed diffuse edema and severe erythema and desquamations at her first visit, 1 week before treatment with GMA. The severity score of GPP was 12. Center: Edema, erythemas and scales were markedly improved at 6 days after three sessions of GMA. The severity score was 5. Right: The skin conditions were well controlled at 19 days after the last GMA session. The severity score was 4.
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F1
Her daughter had arthritis with a high anti-nuclear antibody (ANA) titer (x1,240), but her diagnosis was not established (fig. 1a). On examination, edematous generalized erythroderma with exudations and scales was seen, but pustules were absent (fig. 1b, left). At 6 days after the last GMA, the severity score for GPP had improved to 5 (fig. 1b, center). Further sessions of GMA were held, and neutrophils recovered to normal levels by 19 days, at which time the GPP severity score was 4 (fig. 1b, right).
a Erythemas with multiple pustules and pus lakes at the onset of GPP. b Histology of a lesion. Infiltrates of neutrophils into the epidermis and a spongiform pustule of Kogoj are evident. Scale bar = 50 microm.
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F2
Cyclosporine was effective and the dose was decreased to 100 mg daily, but 2 weeks later, a sudden fever, generalized edema, erythroderma with multiple pustules and lakes of pus occurred (fig. 2a). A skin biopsy showed infiltrates of neutrophils into the upper spinous and subcorneal layers of the epidermis which formed a Kogoj spongiform pustule (fig. 2b).
IL-36RN mutations of the present case (a) and her daughter (b). Arrows indicate each mutation of c.[28C>T];[28C>T] (a) and c.[28C>T];[=] (b), respectively, in IL36RN.
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F3
Genetic analysis revealed homozygous mutations c.[28C>T];[28C>T] which led to p.[Arg10Ter];[Arg10Ter] in the patient (fig. 3a). Her daughter had a heterozygous mutation c.[28C>T];[=] in IL36RN (fig. 3b).
Serum cytokine levels in the course of the case. Blood was sampled 1 week and 1 day before the first session of GMA, 2 days after the second session of GMA and 19 days after the last session of GMA. Concentrations of serum cytokines, IL-6, TNF-alpha, IL-1beta and IL-8 were measured using Bio-Plex Pro human cytokine multiplex assay kits (Bio-Rad, Hercules, Calif., USA) and a Bio-Plex 200 System with high-throughput fluidics (Bio-Rad). The severity score of GPP for each day is indicated. The serum levels of IL-1 and IL-6 decreased with the improvement of GPP.
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F4
TNF-alpha were examined at the patient's first visit, 1 day before the first session of GMA, 2 days after the second session of GMA and 19 days after the last session of GMA (fig. 4).