Alopecia Areata: Case report and review of pathophysiology and treatment with Jak inhibitors.

Alopecia Areata (AA) is a T-cell mediated autoimmune attack on hair follicles resulting in rapidly developing areas of hair loss involving the scalp and beard that can progress to total scalp hair loss (alopecia totalis) and loss of eyebrows, eyelashes, and total body hair (alopecia universalis). Affected patients have high rates of psychological disorders and decreased quality of life. There are no FDA approved treatments, and the available treatments have a high failure rate. JAK inhibitors are remarkably effective in many autoimmune diseases including Alopecia Areata. Presented is a case report of successful treatment with tofacitinib, and a literature review of the pathophysiology of alopecia areata, the mechanism of action of JAK inhibitors, and the JAK inhibitors in phase 2 and 3 trials.

Somatic ATP2A2 mutation in a case of papular acantholytic dyskeratosis: mosaic Darier disease.

Papular acantholytic dyskeratosis, also known as acantholytic dermatosis of the vulvocrural (or anogenital) area, is an uncommon eruption reported predominantly in women. This entity manifests with pruritic papules in the groin/anogenital area and less commonly on the chest. The pathobiology of papular acantholytic dyskeratosis is uncertain. A 62-year-old woman presented with multiple verrucous-appearing lesions in the groin and on the chest showing acantholytic dyskeratosis on histopathology. Given histological similarity of these papular acantholytic dyskeratosis lesions to Darier disease due to inherited ATP2A2 mutation, we screened affected and normal tissue and peripheral blood in our patient for mutations in ATP2A2. We found an identical ATP2A2 p.706D>N mutation in multiple independent papular acantholytic dyskeratosis lesions that was not present in uninvolved skin or peripheral blood DNA. These findings establish somatic mosaicism of ATP2A2 mutations as a genetic cause for papular acantholytic dyskeratosis.

Harms unknown: health uncertainties cast doubt on the role of unconventional gas in Australia's energy future.

There is a push to increase production of unconventional gas in Australia, which would intensify the use of the controversial technique of hydraulic fracturing. The uncertainties surrounding the health implications of unconventional gas, when considered together with doubts surrounding its greenhouse gas profile and cost, weigh heavily against proceeding with proposed future developments. The health and environmental impacts of hydraulic fracturing have been the source of widespread public concern. A review of available literature shows a considerable degree of uncertainty, but an emerging consensus about the main risks. Gas is often claimed to be a less climate-damaging alternative to coal; however, this is called into question by the fugitive emissions produced by unconventional gas extraction and the consequences of its export. While the health effects associated with fracturing chemicals have attracted considerable public attention, risks posed by wastewater, community disruption and the interaction between exposures are of also of concern. The health burdens of unconventional gas are likely to fall disproportionately on rural communities, the young and the elderly. While the health and environmental risks and benefits must be compared with other energy choices, coal provides a poor benchmark.

Case experience of 308-nm excimer laser therapy compatibility with PUVA and oral bexarotene for the treatment of cutaneous lesions in mycosis fungoides.

Little is known about the safety and effectiveness of excimer laser therapy when used in conjunction with other therapies in the treatment of mycosis fungoides (MF) lesions. We describe the use of adjunctive excimer laser therapy in combination with psoralen plus ultraviolet A (PUVA) and oral bexarotene for the treatment of recalcitrant and sanctuary plaques in a patient with MF. In our patient, this regimen successfully induced clinical and histologic resolution in MF plaques with minimal side effects limited to mild, short-lived tenderness and, rarely, local erythema. Our experience suggests that adjunctive excimer laser therapy with PUVA and oral bexarotene has the potential to be a safe, well-tolerated, and effective focal treatment regimen for cutaneous MF lesions.

Role of macrophage migration inhibitory factor in the Th2 immune response to epicutaneous sensitization.

We examined the role of macrophage migration inhibitory factor (MIF) in the generation of the Th2 response using MIF-deficient mice in a model of epicutaneous sensitization to ovalbumin. Lymph node cells from sensitized MIF-deficient mice produce lower levels of Th2 cytokines after antigen challenge when compared to their wild-type counterparts. Sensitized mice lacking MIF show less pulmonary inflammation after intranasal antigen exposure. Mice deficient in CD74, the MIF receptor, also are unable to generate an inflammatory response to epicutaneous sensitization. Examination of the elicitation phase of the atopic response using DO11.10 OVA TCR transgenic animals shows that T cell proliferation and IL-2 production are strongly impaired in MIF-deficient T cells. This defect is most profound when both T cells and antigen-presenting cells are lacking MIF. These data suggest that MIF is crucial both for the sensitization and the elicitation phases of a Th2-type immune response in allergic disease.

Fibrillar IgA deposition in dermatitis herpetiformis--an underreported pattern with potential clinical significance.

Dermatitis herpetiformis has characteristic clinical and histopathologic findings. A fibrillar pattern of IgA deposition on direct immunofluorescence in dermatitis herpetiformis is underreported. Here, we describe three patients with the fibrillar pattern of IgA deposition on direct immunofluorescence examination that initially misled diagnosis in one of the three. Interestingly, two of the three patients lacked anti-transglutaminase and anti-endomysial antibodies but had a clinical course typical of dermatitis herpetiformis. Dermatitis herpetiformis may have a fibrillar rather than granular pattern of IgA deposition on direct immunofluorescent microscopy, and patients with this pattern of immunoglobulin deposition may lack circulating autoantibodies.

Calcinosis cutis: a complication of intravenous administration of calcium glucanate.

Calcinosis cutis, the deposition of calcium in the dermis, can be dystrophic, metastatic, iatrogenic, or idiopathic. Here, we describe a case of iatrogenic calcinosis cutis secondary to extravasation of an intravenous calcium-containing solution in a child. We also review the literature regarding the pathogenic mechanisms involved in the development of calcinosis cutis after extravasation injuries. While iatrogenic calcinosis cutis is generally a benign entity, it is important to recognize its unique clinical and histopathologic presentation to avoid complications from misdiagnosis.

Diterpenoid, steroid, and triterpenoid agonists of liver X receptors from diversified terrestrial plants and marine sources.

It has been demonstrated that liver X receptors (LXR) play a significant role in cholesterol homeostasis. Agonists of LXR are expected to increase cellular cholesterol efflux, lower LDL, and raise HDL levels. Screening of a natural product library of plant extracts using a LXR-SPA binding assay and bioassay-guided fractionation of a number of plant and marine gorgonian extracts led to the isolation of a number of active compounds. These included acanthoic acid (1) and alcohol (2), viperidone (3), polycarpol (4), rosacea acid (5), a cycloartane derivative (6), a new cycloartane analogue (7), betulinic acid (8), and gorgostane derivatives (9, 10, and 11). Of these compounds, 1, 4, and 11 exhibited potent binding affinity for alpha-receptor with IC(50) values of 0.25, 0.12, and 0.07 microM, respectively. Functionally they also showed strong coactivator association stimulation for LXRalpha receptor with EC50 values of 0.18, 0.03, and 0.05 microM, respectively. They also exhibited 15-, 8-, and 13-fold induction of the alpha-receptor in a transactivation assay in HEK-293 cells, respectively. In general these compounds were selective for the LXR alpha-receptor over the beta-receptor in all assays and were much better stimulators of the alpha-receptor than the endogenous steroid ligands.

The ShiA protein encoded by the Shigella flexneri SHI-2 pathogenicity island attenuates inflammation.

Shigella spp. are the aetiologic agents of dysentery, a severe diarrhoeal syndrome characterized by acute inflammation in the colon. The inflammatory response, which includes recruitment of polymorphonuclear leukocytes (PMN), damages the colonic mucosa and exacerbates the infection. Shigella encodes a pathogenicity island (PAI), SHI-2, which is localized in a region of the chromosome linked to the induction of inflammation. Surprisingly, SHI-2 deletion mutants induce a stronger inflammatory response than wild-type Shigella as measured by increased villus blunting, increased PMN infiltration and induction of apoptosis in a rabbit ileal loop model of shigellosis. Mutational analysis mapped the hyper-inflammatory phenotype to a single gene, shiA. Similar to SHI-2 deletion mutants, infection with a shiA mutant strain induces dramatically elevated levels of inflammation when compared to the wild-type strain. Furthermore, infection with a wild-type strain containing multiple copies of shiA results in fewer infiltrating PMN and apoptotic cells, as well as preservation of a normal villus architecture at the site of infection, thus acting in a dominant fashion over the pro-inflammatory mechanisms of Shigella. The molecular mechanism of action of ShiA is independent of any in vitro phenotype associated with Shigella virulence. Our data suggest that ShiA allows Shigella to attenuate the host inflammatory response in a novel manner.