Bullous Variant of Sweet's Syndrome after Herpes Zoster Virus Infection

Aim: Cutaneous manifestations of Sweet’s syndrome (SS) are typically painful plaque-forming erythematous papules, while bullae are quite uncommon. We present a case of bullous variant of SS in acute myeloid leukaemia. In this case, herpes infection of the left mandible had preceded the development of SS. Case Report: A 75-year-old male with myelodysplastic syndrome first presented with herpes zoster virus infection-like bullae and erosive plaques on the left side of the face and neck. Treatment with valacyclovir and antibiotics was effective only for the initial lesions, whereas the other bullae kept developing predominantly on the left side. Histopathological study revealed epidermal bulla formation, pandermal neutrophilic infiltration, erythrocyte extravasation and subepidermal oedema, but no vasculitis. The findings suggested the diagnosis of bullous variant of SS. Discussion: Our case was unique in that bullous SS symptoms developed predominantly on one side of the cheek and neck where the herpes zoster infection occurred prior to SS. The tendency may explain the possible association between viral infection and development of SS

Electrically evoked itch in humans

Abstract We compared itch sensations and axon reflex flare induced by transcutaneous electrical (0.08-8 ms, 2-200 Hz) and chemical (histamine iontophoresis; 100 mC) stimulation. Stimuli were applied to non-lesional volar wrist skin in 20 healthy human subjects and 10 patients with atopic dermatitis. Intensity of evoked itch and pain sensations were rated on a numerical rating scale (NRS) of 0 (no sensation) to 10 (the maximum sensation imaginable). The axon reflex erythema was measured by laser Doppler imager and areas of alloknesis (itch evoked by light brushing) and hyperknesis (itch evoked by pricking) were assessed psychophysically. Electrical stimulation was most effective for stimulus durations R2 ms and frequencies R50 Hz. It evoked pure itch as threshold sensation in 80% of the subjects that was perceived with a delay of approximately 1 s. Itch intensities of up to 7/10 were not accompanied by an axon reflex flare. In contrast, histamine provoked a massive increase of axon reflex erythema and maximum itch ratings of 3.1G0.2. The extention of alloknesis areas (2.3G0.5 cm) evoked by electrical stimulation clearly exceeded those induced by histamine (0.7G0.3 cm). Healthy subjects and patients with atopic dermatitis did not differ significantly in their response to either stimulation. We conclude that C-fiber activation underlies the electrically evoked itch sensation. The low electrical thresholds and the absence of an axon reflex flare suggest that these fibers are not identical with the previously described mechano-insensitive histamine responsive C fibers, but represent a separate peripheral neuronal system for the induction of itch.

Upregulation of Aquaporin-3 Is Involved in Keratinocyte Proliferation and Epidermal Hyperplasia

Aquaporin-3 (AQP3) is a water/glycerol-transporting protein expressed in keratinocytes of the epidermis. We previously showed that AQP3-mediated transport of water and glycerol is involved in keratinocyte migration and proliferation, respectively. However, the involvement of AQP3 in epidermal hyperplasia in skin diseases, such as atopic dermatitis (AD), is unknown. In this study, we found significantly increased AQP3 transcript and protein expression in the epidermis of human AD lesions. The upregulation of AQP3 expression in human keratinocytes by transfection with human AQP3 DNA plasmid was associated with increased cellular glycerol and ATP, as well as increased cell proliferation. Among several cytokines and chemokines produced in the skin, CCL17, which is highly expressed in AD, was found to be a strong inducer of AQP3 expression and enhanced keratinocyte proliferation. In mouse AD models, AQP3 was strongly overexpressed in the epidermis in wild-type mice. Epidermal hyperplasia was reduced in AQP3-deficient mice, with a decreased number of proliferating keratinocytes. These results suggest the involvement of AQP3 in epidermal hyperplasia by a mechanism involving upregulated AQP3 expression and consequent enhancement of keratinocyte proliferation

Myeloperoxidase-Antineutrophil Cytoplasmic Antibody-Negative Microscopic Polyangiitis with Pulmonary Haemorrhage and IgA Nephropathy

Aim: To report a case of a patient with myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA)-negative microscopic polyangiitis (MPA) and IgA nephropathy associated with severe pulmonary haemorrhage. Case Report: A 59-year-old man presented with ANCA-negative systemic vasculitis accompanied by purpura, nephritis and pulmonary haemorrhage. A skin biopsy specimen revealed pandermal leucocytoclastic vasculitis without IgA deposition and a kidney biopsy showed mesangial nephritis with IgA deposition. Considering these findings, the patient was diagnosed as having MPA with IgA nephropathy. Discussion: In most cases, MPA presents with rapidly progressive necrotizing glomerulonephritis and sometimes lung haemorrhage, while IgA nephropathy is less common among MPA cases. As recent research suggested that in MPA immunoglobulin deposition in the kidney may be an exacerbating factor for renal dysfunction and poor prognosis, close observation is required in these cases

Characterization of Tight Junctions and Their Disruption by UVB in Human Epidermis and Cultured Keratinocytes

It has not been confirmed whether tight junctions (TJs) function as a paracellular permeability barrier in adult human skin. To clarify this issue, we performed a TJ permeability assay using human skin obtained from abdominal plastic surgery. Occludin, a marker protein of TJs, was expressed in the granular layer, in which a subcutaneously injected paracellular tracer, Sulfo-NHS-LC-Biotin (556.59Da), was halted. Incubation with ochratoxin A decreased the expression of claudin-4, an integral membrane protein of TJs, and the diffusion of paracellular tracer was no longer prevented at the TJs. These results demonstrate that human epidermis possesses TJs that function as an intercellular permeability barrier at least against small molecules (∼550Da). UVB irradiation of human skin xenografts and human skin equivalents (HSEs) resulted in functional deterioration of TJs. Immunocytochemical staining of cultured keratinocytes showed that occludin was localized into dot-like shapes and formed a discontinuous network when exposed to UVB irradiation. Furthermore, UVB irradiation downregulated the active forms of Rac1 and atypical protein kinase C, suggesting that their inactivation caused functional deterioration of TJs. In conclusion, TJs function as a paracellular barrier against small molecules (∼550Da) in human epidermis and are functionally deteriorated by UVB irradiation

Facilitation of Th1-mediated immune response by prostaglandin E receptor EP1

Prostaglandin E2 (PGE2) exerts its actions via four subtypes of the PGE receptor, EP1–4. We show that mice deficient in EP1 exhibited significantly attenuated Th1 response in contact hypersensitivity induced by dinitrofluorobenzene (DNFB). This phenotype was recapitulated in wild-type mice by administration of an EP1-selective antagonist during the sensitization phase, and by adoptive transfer of T cells from sensitized EP1−/− mice. Conversely, an EP1-selective agonist facilitated Th1 differentiation of naive T cells in vitro. Finally, CD11c+ cells containing the inducible form of PGE synthase increased in number in the draining lymph nodes after DNFB application. These results suggest that PGE2 produced by dendritic cells in the lymph nodes acts on EP1 in naive T cells to promote Th1 differentiation