Case of toxic epidermal necrolysis occurring after bone marrow transplantation accompanied by engraftment failure.

Toxic epidermal necrolysis (TEN) is a rare condition, causing life-threatening adverse cutaneous reactions. TEN occurrence after bone marrow transplantation (BMT) is a well-known phenomenon; however, to date, only a few cases have been reported in the published work. Here, we describe the case of a 53-year-old woman who experienced TEN after undergoing allogenic BMT for malignant lymphoma. Skin erosion spread across a maximum of 70% of the body surface area and severe mucosal lesions developed. Steroid pulse therapy, plasma apheresis and immunoglobulin therapy were administrated, which resulted in the complete resolution of TEN. However, she developed hemophagocytic lymphohistiocytosis and died 38 days after BMT, owing to rupture of the lower digestive tract complicated by multi-organ failure. In our case, engraftment failure occurred, and the peripheral white blood cell count was less than 100/µL during the TEN course, suggesting that the presence of only a few immune cells could cause TEN. Our findings showed that high mortality rates and widespread skin erosion could be regarded as the most important characteristics of TEN occurring after BMT.

Serum levels of squamous cell carcinoma antigens 1 and 2 reflect disease severity and clinical type of atopic dermatitis in adult patients.

BACKGROUND: Recent studies have indicated that serum levels of squamous cell carcinoma antigen (SCCA) 1 and 2 induced by type 2 cytokines such as IL-4 and IL-13, are increased in patients with atopic dermatitis (AD). However, no clinical studies have analyzed serum levels of SCCA2 in larger series of AD patients or their association with various clinical characteristics. This study was performed to clarify whether serum levels of SCCA2 are associated with disease severity and clinical phenotypes of adult AD patients. METHODS: An enzyme-linked immunosorbent assay was performed to examine serum SCCA2 levels in 240 adult patients with AD and 25 healthy controls in this study. Serum SCCA2 levels were analyzed with clinical characteristics and laboratory parameters including thymus and activation-regulated chemokine (TARC), lactate dehydrogenase (LDH), blood eosinophils, total IgE, and specific IgE (Japanese cedar pollen, Dermatophagoides farina, Candida, malassezia, Staphylococcal enterotoxin B). Expression of SCCA2 in AD eruption was examined by immunohistochemistry. The effect of treatment on serum SCCA2 was also assessed. RESULTS: Serum SCCA2 level showed a positive correlation with disease severity, levels of TARC, LDH, eosinophil counts, and IgE levels. Robust expression of SCCA2 was detected in the supra basal keratinocytes in the epidermis of AD patients. Serial measurements of serum SCCA2 revealed decreased levels of SCCA2 after treatment for AD. CONCLUSIONS: Serum SCCA2 levels reflected disease severity and clinical type of AD. Serum SCCA2 may thus be a relevant biomarker for AD.

Anti-inflammatory effect of collagen tripeptide in atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin disease in which type 2 allergic inflammation plays an important role. Collagen tripeptide (CTP) is a functional collagen fraction with a high content of Gly-X-Y tripeptides. OBJECTIVE: To examine the effect of CTP on inflammation in AD. METHODS: Levels of inflammatory cytokines and chemokines, such as thymus- and activation-regulated chemokine (TARC), macrophage-derived chemokine, and thymic stromal lymphopoietin (TSLP), were examined in human keratinocytes supplemented with or without CTP under AD-like inflammation. To evaluate the functional effect of CTP, a migration assay was performed using the supernatants of cultured keratinocytes treated with CTP. The signaling pathway for CTP inhibitory activity was also determined. Additionally, we conducted a clinical trial with seventeen AD patients who were assigned randomly to receive daily for 12 weeks either 3.9g of a CTP product or normal collagen peptides (CP). The eruption area, severity scoring of atopic dermatitis (SCORAD), skin hydration, transepidermal water loss (TEWL), and itching score were evaluated. The levels of TARC, serum IgE, lactate dehydrogenase, and eosinophil counts at week 12 were also compared with those at the start of administration. RESULTS: In human keratinocytes, TARC and TSLP mRNA and protein levels were inhibited significantly by CTP treatment under AD-like inflammation. Supernatants obtained from CTP-treated keratinocytes inhibited cell migration. STAT1 phosphorylation was significantly decreased by CTP in a dose-dependent manner. In the clinical trial, 13 patients (7 for CTP, 6 for CP) completed the study. The eruption area, SCORAD, and TEWL at week 12 were reduced significantly compared with the initial values in the CTP but not CP group. A significant reduction in the serum TARC level was observed only in the CTP group at week 12. Other blood parameters were not improved in either group. CONCLUSION: CTP may have therapeutic benefit for AD by inhibiting type 2-skewed allergic inflammation.

Case of subepidermal autoimmune bullous disease with psoriasis vulgaris reacting to both BP180 C-terminal domain and laminin gamma-1.

A number of cases of psoriasis vulgaris developing bullous skin lesions have been diagnosed as either bullous pemphigoid with antibodies to the 180-kDa bullous pemphigoid antigen (BP180) non-collagenous 16a (NC16a) domain or anti-laminin-γ1 (p200) pemphigoid. We report a case of subepidermal bullous disease with psoriasis vulgaris, showing antibodies to both BP180 C-terminal domain and laminin-γ1. A 64-year-old Japanese man with psoriasis vulgaris developed exudative erythemas and tense bullae on the whole body but he did not have mucosal involvement. The blistering lesion showed subepidermal blisters histopathologically. In indirect immunofluorescence of 1 mol/L NaCl-split skin, immunoglobulin (Ig)G antibodies reacted with both the epidermal and dermal side. Immunoblotting showed positive IgG with recombinant protein of BP180 C-terminal domain and 200-kDa laminin-γ1 in normal human dermal extract.

Oral administration of collagen tripeptide improves dryness and pruritus in the acetone-induced dry skin model.

BACKGROUND: Dry skin causes pruritus and discomfort in patients with xerosis and atopic dermatitis. General treatment for skin dryness involves the topical application of an emollient. However, more effective, simpler therapies are desired. Collagen tripeptide (CTP) is a highly purified, non-antigenic, low-allergenic collagen fraction that is known to have various biological effects. OBJECTIVE: To clarify the therapeutic effects of CTP for dry skin using acetone-induced dry skin model mice. METHODS: ICR mice were treated with acetone followed by oral administration of CTP (80 or 500mg/kg/day) for 3 days. Hyaluronic acid production induced by CTP was assessed using human dermal fibroblasts in vitro and in an acetone-induced dry skin model mice in vivo. Transepidermal water loss (TEWL) and scratching behavior were evaluated. Furthermore, the effects of CTP on intraepidermal nerve fibers and expression of semaphorin 3A (Sema3A) and nerve growth factor (NGF) were examined by immunohistochemistry and quantitative RT-PCR. RESULTS: CTP enhanced hyaluronic acid production in human dermal fibroblasts in vitro and in murine skin in vivo. Oral administration of CTP in acetone-induced dry skin model mice significantly decreased TEWL and suppressed scratching behavior. Intraepidermal nerve growth was dramatically inhibited in CTP-treated mice. Quantitative PCR analysis and immunohistochemical study revealed that CTP abolished the increased NGF and decreased Sema3A levels induced by acetone treatment. CONCLUSION: Oral administration of CTP improves dry skin and normalizes axon-guidance factors in the epidermis in addition to reducing pruritus. CTP may be used in a new therapeutic strategy against dry skin and pruritus.

[A case of an allergic reaction due to Anisakis simplex after the ingestion of salted fish guts made of Sagittated calamari: allergen analysis with recombinant and purified Anisakis simplex allergens].

A 75-year-old man ingested salted fish guts made of Sagittated calamari which he caught in the daytime, with alcohol and then dozed. Five hours later, he woke up due to itching over his entire body and noticed generalized urticaria and a swollen tongue, which was too large for him to close his mouth. Serum total IgE was 456 IU/ml and ImmunoCAP was positive for anisakis, but negative for squid, shrimp, and ascaris. A skin prick test (SPT) was positive for anisakis extract (10 mg/ml) and house dust mites, but negative for squid and shrimp. He was diagnosed with IgE-mediated allergy due to Anisakis simplex after the ingestion of salted fish guts made of Sagittated calamari, which had been parasitized by Anisakis simplex. Furthermore, we performed SPT with six extracts of purified or recombinant allergens (Ani s 1, 3, 4, 5, 6, and 8) to identify the causative allergens in this case. Only Ani s 3 (tropomyosin) was positive, indicating that Ani s 3 was the causative allergen in this case. Third stage larvae of the nematode Anisakis simplex often parasitize not only marine fish but also invertebrates, including squid. It is necessary to consider Anisakis simplex allergy for urticarial reactions that develop after the ingestion of squid.

[Case of food-dependent exercise-induced anaphylaxis diagnosed by the provocation test with cuttlefish after the pretreatment with 1.5 g of aspirin].

A 29-year-old woman had an episode of urticaria at the age of 17 while exercising after eating fried cuttlefish. For years thereafter, she experienced several episodes of urticaria after eating seafood. At the age of 29, she ate grilled seafood, including cuttlefish for supper after taking loxoprofen for lumbago. One hour later, she developed generalized urticaria accompanied by nausea, abdominal pain, swelling of the lips, and dyspnea while walking; she was taken to a hospital. She was then referred to us for further examination of the etiology of her anaphylactic reactions. The level of specific IgE measured using Immuno CAP was negative for all kinds of foods, including cuttlefish. However, a skin prick test was positive for raw and cooked cuttlefish. Provocation tests were performed on admission by combining the intake of cuttlefish and aspirin under the suspicion of cuttlefish allergy enhanced by nonsteroidal anti-inflammatory drugs and exercise. As a result, she developed no symptoms except for slight itching of the oral mucosa after eating 20 g or 100 g of cuttlefish with or without concomitant administration of 0.5 g of aspirin. Finally, generalized urticaria appeared after challenge with cuttlefish and 1.5 g of aspirin. She was diagnosed with food-dependent exercise-induced anaphylaxis (FDEIA) caused by cuttlefish. She has not developed urticaria since she started to avoid eating cuttlefish. Our results indicated that in provocation tests for the diagnosis of FDEIA, allergic reactions could not only be induced by food intake but could also be enhanced by aspirin in a dose-dependent manner.