Eosinophilic fasciitis (EF) with generalized sclerodermiform skin lesions developed over a 19-month period in a previously healthy 23-year-old man. Although we confirmed EF by skin histology and laboratory tests, the recurrent fevers and the clinical observation of sclerotic prepuce with urethritis indicated further bacteriological analysis by conventional microbiological and DNA-based tests. Urethra cultures were positive for an arginine-hydrolyzing mycoplasma and Ureaplasma urealyticum. The patient also had serum IgM antibodies to Mycoplasma pneumoniae using enzyme-linked immunosorbent assay (ELISA)-based qualitative detection. Mycoplasma arginini was isolated from two independent venous blood serum samples and was identified by conventional microbiological tests and sequencing of the 16S rRNA and rpoB genes (GenBank sequence accession numbers HM179555 and HM179556, respectively). M. arginini genomic DNA also was detected by species-specific PCR in the skin lesion biopsy sample. Treatment with corticosteroids and long-term courses of selected antibiotics led to remission of skin symptoms and normalization of laboratory values. This report provides the first evidence of EF associated with mycoplasma infection and the second report of human infection with M. arginini and therefore suggests that this mycoplasma infection might have contributed to the pathogenesis of the disease. CASE REPORTA 23-year-old male, a former bodybuilder, sought medical treatment for progressive generalized skin tightening. His previous medical history was unremarkable. The patient had terminated sport exercises 19 months earlier due to a sudden, progressive skin induration, which led to restricted movement of wrists and ankles within several months, and cutaneous symptoms gradually extended to the extremities and to the upper body. At the beginning of his illness, he quit body building and stopped anabolic steroid consumption. Within 1 year, he lost 23 kg, he became febrile in the afternoons, and his skin disease slowly progressed. Serological tests for HIV, hepatitis C virus (HCV), and Lyme borreliosis were negative. His crista biopsy specimen revealed eosinophilia. The patient was treated with a very low dose of prednisone (10 mg/day orally [p.o.]) for the next 6 months without dermatological improvement. Any attempt to decrease the prednisone dosage resulted in return of arthralgia and fever.Upon initial examination, the patient suffered from generalized skin tightening and tautness on his whole trunk and on all the extremities except the fingers and toes. He also exhibited multiple cutaneous venous furrowing on the arms (Fig. 1). The shiny, brownish, firm skin with some porcelain-whitish patches was tightly bound to the underlying tissues, resulting in a restricted movement of the chest, wrists, elbows, ankles, and knees. The genital region was also involved; the indurated, sclerotic, depigmented prepuce led to phimosis and showed lichen sclerosus-like symptoms with an inflamed urethral orifice.Initial laboratory tests showed periph...
The estimated age of the mutation corresponds to the time period when Roma were wandering in the Balkans.
The Type Ia supernova (SN Ia) 2017cfd in IC 0511 (redshift z = 0.01209 ± 0.00016) was discovered by the Lick Observatory Supernova Search 1.6 ± 0.7 d after the fitted first-light time (FFLT; 15.2 d before B-band maximum brightness). Photometric and spectroscopic follow-up observations show that SN 2017cfd is a typical, normal SN Ia with a peak luminosity M B ≈ −19.2±0.2 mag, ∆m 15 (B) = 1.16 mag, and reached a B-band maximum ∼16.8 d after the FFLT. We estimate there to be moderately strong host-galaxy extinction (A V = 0.39 ± 0.03 mag) based on MLCS2k2 fitting. The spectrum reveals a Si II λ6355 velocity of ∼ 11, 200 km s −1 at peak brightness. SN 2017cfd was discovered very young, with multiband data taken starting 2 d after the FFLT, making it a valuable complement to the currently small sample (fewer than a dozen) of SNe Ia with color data at such early times. We find that its intrinsic early-time (B − V ) 0 color evolution belongs to the "blue" population rather than to the distinct "red" population. Using the photometry, we constrain the companion star radius to be 2.5 R , thus ruling out a red-giant companion.
signals. Topical application of E6005 did not affect mechanical stimulation-evoked nerve activity, suggesting that the inhibitory effects of E6005 are not due to nervous damage or local anaesthetic action.The cutaneous concentration of cAMP was decreased in mice with dermatitis, and topical E6005 application reversed the decreased concentration. PDE4 is expressed in the keratinocytes (16). Thus, it is possible that the activation of PDE4 (a decrease in the cAMP concentration) in the epidermal keratinocytes is responsible for chronic dermatitis-associated itching and that the inhibition of activated PDE4 relieves the itching. The mechanisms of the cAMP-mediated antipruritic effect remain unclear. Protein kinase A inactivates 5-lipoxygenase through the phosphorylation of its Ser 523 residue, leading to a decrease in leukotriene B 4 production (17). Leukotriene B 4 is a potent itch mediator (18) acting on the BLT1 leukotriene B 4 receptor in primary afferents (19). Leukotriene B 4 produced in keratinocytes is involved in spontaneous scratching in mice with dermatitis (5) and proteinase-activated receptor 2-mediated scratching (20). Thus, it is conceivable that an increase in cAMP concentration by E6005 results in the inhibition of increased production of leukotriene B 4 in keratinocytes in dermatitis.Tryptase release from mast cells is increased in the lesioned skin of patients with atopic dermatitis (21) and NC mice with chronic dermatitis (4). PDE4 inhibitors suppress the degranulation of mast cells through the increase in intra-cellular cAMP (22). Inflammatory cells including T cells are increased in the skin of NC mice with dermatitis (23), T-cell cytokines including interleukin-31 are associated with scratching (2,24), and PDE4 inhibitors suppress the activation and cytokine release of these cells (25). Thus, the anti-inflammatory actions may also contribute to the antipruritic effects of E6005. Sensory C-fibres play an important role in spontaneous scratching in NC mice with dermatitis (26). The sensitivity of C-fibres to heat and chemical stimuli are increased or not affected by cAMP (27), and protein kinase A activation reduces TRPV1 channel desensitization (28). Thus, the direct action of E6005 on primary afferents may not play a role in its antipruritic effect.The present study showed that E6005, a novel PDE4 inhibitor, has acute antipruritic activity in chronic dermatitis. Thus, E6005 is expected to be useful for the treatment of pruritic chronic dermatitis including atopic dermatitis. AcknowledgementsThis study was funded by Eisai Co. Ltd. Tokyo, Japan. Author contributionsTA and YK designed experiments, and TA and TY performed experiments. TA and YK wrote the manuscript. Conflict of interestsThe authors do not report any conflict of interest relevant to this study. Supporting InformationAdditional Supporting Information may be found in the online version of this article: Data S1. Methods. Figure S1. Hind-paw scratching following topical application of vehicle for E6005 in mice. Figure S2. E6005 does n...
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