Background Hidradenitis suppurativa (HS) is a debilitating inflammatory skin disease characterized by painful nodules, drainage and scarring in skin folds. Injectable adalimumab is the only drug approved by the US Food and Drug Administration for the treatment of HS. Although systemic Janus kinase (JAK) inhibitors show promise, serious side-effects have been reported. There are no highly effective topical treatments for HS; furthermore, the contribution of epidermal keratinocytes to the intense inflammation has largely been unexplored. Objectives We investigated the role of keratinocytes and epidermal immune cells in HS inflammation at all Hurley stages of disease severity. We aimed to determine whether ruxolitinib can mitigate inflammation from keratinocytes and to develop a better understanding of how topical therapeutics might benefit patients with HS. Methods We used skin samples from 87 patients with HS (Hurley stages I–III) and 39 healthy controls to compare keratinocyte- and immune cell-driven epidermal inflammation, in addition to the response of lesional HS keratinocytes to treatment with interferon (IFN)-γ and ruxolitinib. We used haematoxylin and eosin staining, immunohistochemistry, immunoblotting and quantitative reverse-transcription polymerase chain reaction assessments in whole skin, isolated epidermis, and cultured keratinocytes from healthy controls and both nonlesional and lesional HS skin to identify and define epidermal and keratinocyte-mediated inflammation in HS and how this may be targeted by therapeutics. Results HS lesional keratinocytes autonomously secreted high levels of chemokines, such as CCL2, CCL3 and CXCL3, which recruited neutrophils, CD8 T cells, and natural killer cells to the epidermis. Keratinocytes were the dominant source of tumour necrosis factor-α and interleukin (IL)-6 in HS lesions with little to no contribution from underlying dermal immune cells. In the presence of IFN-γ, which is dependent on immune cell infiltrate in vivo, keratinocytes expressed increased levels of additional cytokines including IL-1β, IL-12, IL-23 and IL-36γ. The JAK inhibitor ruxolitinib mitigated the expression of inflammatory cytokines and chemokines in HS lesional keratinocytes, thus providing a rationale for future study as a topical treatment for HS. Conclusions This study demonstrates that keratinocytes actively recruit immune cells to HS epidermis and interactions between these cells drive a broad inflammatory profile in HS epidermis. Targeting epidermal inflammation in HS with novel topical formulations may be highly efficacious with reduced systemic side-effects.
Metastatic melanoma may exhibit clinical or histologic features of blue nevus. Pembrolizumab therapy is associated with regression and tumoral melanosis. We report on a man with widespread metastatic melanoma on pembrolizumab therapy in whom a blue-grey papule developed on the left side of his neck that clinically resembled a blue nevus and histologically showed features of both blue nevus and tumoral melanosis. The subtle melanocytic component and prominent changes of regression evident on biopsy suggest that his immunomodulatory therapy may have influenced the histologic findings noted on biopsy. Physicians that treat patients with metastatic melanoma should be aware of the spectrum of histologic findings evident on biopsy not only to allow for early diagnosis but to also better understand the effects of treatment.
Long-distance running has evolved into a sport that continues to gain in popularity. Skin problems are common among long distance runners and may prompt athletes to seek medical attention. This paper reviews the skin problems of long distance runners and outlines treatments that we have found to be helpful.
Introduction: Allergic reactions to metal implants are increasingly recognized, but its relevance to the orthopaedic surgeon remains unclear. We evaluate the prevalence of metal allergies in a subset of the population and review the significance through a survey of the current literature. Methods: Preoperative and postoperative patients referred for metal allergy testing were divided into two groups; those with a history of dermatitis and those without. Patients with a history of dermatitis were offered skin patch testing that included the North American Contact Dermatitis core allergen panels in addition to our metal screening series. Patients without dermatitis were tested to the more limited patch testing metal screening series. Some patients with dermatitis opted for the more limited screening, whereas some patients without dermatitis underwent more extensive testing at their request or at the request of the referring clinician. Patch tests were evaluated at 2 and 4 days after placement. Results: Hundred patients were referred for metal allergy testing, 46 of whom were for reasons related to planned orthopaedic surgery. Of those tested, 60 patients had a history of dermatitis and 40 did not. Some patients were nonreactive to all tested allergens, whereas others demonstrated one or more positive skin patch test reactions. The number of positive reactions to each metal in patients with a history of dermatitis was the following: nickel 19, amalgam 10, palladium 10, copper 8, cobalt 5, mercury 5, tin 2, gold 1, titanium 1, and vanadium 1. The number of positive reactions to metals in patients without a history of dermatitis was the following: nickel 4, amalgam 5, palladium 4, mercury 4, cobalt 4, tin 2, copper 2, gold 1, vanadium 1, and molybdenum 1. Discussion: Metal allergy was common in the individuals referred for testing, with reactions to nickel and amalgam being the most commonly encountered. Some individuals experience more notable allergic reactions to implanted devices than others. Localized and generalized skin reactions have been reported, along with implant failure and loosening. Surgeons should be aware of the incidence of metal allergies and the potential consequences.
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