Junko Murata

Increased soluble Fas ligand levels in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis preceding skin detachment

BACKGROUND It is difficult to distinguish the early phase of Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) from other ordinary types of drug-induced skin reactions (ODSRs). Levels of several serum soluble factors, including soluble Fas ligand (sFasL), have been reported to be increased in patients with SJS/TEN; however, the marker to predict the onset of SJS/TEN before the development of skin detachment or mucosal lesions has not been identified. OBJECTIVE We sought to determine whether sFasL might be a useful marker in the early stages of SJS/TEN. METHODS Sera of 19 patients with SJS and 16 patients with TEN at 1 or multiple time points were obtained from Japanese multiple hospitals. The disease onset (day 1) was defined when erosion/ulceration of the mucocutaneous or ocular lesion first developed. For the investigation of soluble factors, including sFasL, TNF-alpha, IFN-gamma, IL-6, and sCD40 ligand, we used ELISAs and Cytometric Bead Arrays. RESULTS Before disease onset (day -4 to approximately -2), 7 samples were available, and we detected the highest concentrations of sFasL in 5 (71.4%) of 7 patients. Increased sFasL levels decreased rapidly within 5 days of disease onset. In all 32 patients with ODSRs and 33 healthy control subjects, no increase of sFasL levels was detected. Other soluble factor concentrations did not show significant difference with those seen in patients with SJS/TEN before disease onset and ODSRs. CONCLUSION The sFasL levels of sera in patients with SJS/TEN are significantly increased before development of skin detachment, mucosal lesions, or both.

Prolonged elevation of serum granulysin in drug‐induced hypersensitivity syndrome

and soluble CD40 ligand in serum and plasma. J Thromb Haemost 2004; 11:2067–9. 6 Kasperska-Zajac A, Sztylc J, Machura E, Jop G. Plasma IL-6 concentration correlates with clinical disease activity and serum C-reactive protein concentration in chronic urticaria patients. Clin Exp Allergy 2011; 41:1386–91. 7 Toubi E, Adir-Shani A, Kessel A et al. Immune aberrations in B and T lymphocytes derived from chronic urticaria patients. J Clin Immunol 2000; 20:371–8. 8 Hermes B, Worm M, Nowak F et al. Upregulation of CD40 and CD40 ligand expression in IgE-associated cutaneous diseases. Acta Derm Venereol 1997; 77:441–5. 9 Kasperska-Zajac A, Rogala B. Platelet activation during allergic inflammation. Inflammation 2007; 30:161–6. 10 Kasperska-Zając A, Rogala B, Nowakowski M. Assessment of platelet activity as expressed by plasma levels of platelet factor 4 and b-thromboglobulin in patients with chronic idiopathic urticaria. Exp Dermatol 2005; 14:515–18. 11 Kasperska-Zajac A, Brzoza Z, Rogala B. Platelet function in cutaneous diseases. Platelets 2008; 19:317–21. 12 Kasperska-Zajac A. Acute phase response in chronic urticaria. J Eur Acad Dermatol Venereol 2011; (in press). 13 Kasperska-Zając A, Grzanka A, Czecior E, Misiolek M, Rogala B, Machura E. Acute phase inflammatory markers in patients with non-steroidal anti-inflammatory drugs (NSAIDs)-induced acute urticaria ⁄angioedema and after aspirin challenge. J Eur Acad Dermatol Venereol 2012; 21 February. doi: 10.1111/j.1468-3083.2012. 04486.x.

Bone Marrow-Derived Cells Are Not the Origin of the Cancer Stem Cells in Ultraviolet-Induced Skin Cancer

Several lines of evidence have demonstrated that various cancers are derived from cancer stem cells (CSCs), which are thought to originate from either tissue stem or progenitor cells. However, recent studies have suggested that the origin of CSCs could be bone marrow-derived cells (BMDCs); for example, gastric cancer, which follows persistent gastric inflammation, appears to originate from BMDCs. Although our previous research showed the capability of BMDCs to differentiate into epidermal keratinocytes, it has yet to be determined whether skin CSCs originate from BMDCs. To assess the possibility that BMDCs could be the origin of CSCs in skin squamous cell carcinoma (SCC), we used a mouse model of UVB-induced skin SCC. We detected a low percentage of BMDCs in the lesions of epidermal dysplasia (0.59%), SCC in situ (0.15%), and SCC (0.03%). Furthermore, we could not find any evidence of clonal BMDC expansion. In SCC lesions, we also found that most of the BMDCs were tumor-infiltrating hematopoietic cells. In addition, BMDCs in the SCC lesions lacked characteristics of epidermal stem cells, including expression of stem cell markers (CD34, high alpha6 integrin) and the potential retention of BrdU label. These results indicate that BMDCs are not a major source of malignant keratinocytes in UVB-induced SCC. Therefore, we conclude that BMDCs are not the origin of CSCs in UVB-induced SCC.

Coexistence of a systemic lupus erythematosus and porphyria cutanea tarda: case successfully improved by avoidance of sun exposure

A 46-year-old Japanese woman pr esented with vesicles on her nose and the dosal aspect of her hands since 3 months. Physical examination revealed tense blisters and atrophic erythematous plaques on her arms and the dosal side of her hands (Fig. 1a). Erosions were also scattered on the face (Fig. 1b). She also had hypertrichosis on her face. The patient was first diagnosed as having systemic lupus erythematosus (SLE) in 1997 at the age of 41 years, when she presented with alopecia, fever, arthralgia, Raynaud’s phenomenon, hemolytic anemia and lymphadenopathy. Liver transamirase levels were slightly elevated. She had no sign of hepatitis including autoimmune hepatitis, drug-rela ted hepatotoxity, al coholic hepatitis, or viral infection. Systemic lupus eryhtematosus was well-controlled with a daily 5-mg dose of prednisolone (PSL). At age of 43 years she developed erythematous plaques with scaling on the back of her hands. Clinically the skin erupution at that time appeared to be discoid lupus erythematodes. She was treated with a steroid ointment and her eruptions gradually improved, but new skin lesions repeatedly appeared on her hands. Laboratory investigations at age 46 years while taking PSL 5mg disclosed the following results: white cell count 3.9 ×10

Recurrent Course and CD30 Expression of Atypical T Lymphocytes Distinguish Lymphomatoid Papulosis From Primary Cutaneous Aggressive Epidermotropic CD8 + Cytotoxic T-cell Lymphoma

© 2014 The Authors. doi: 10.2340/00015555-1806 Journal Compilation