Occupational allergic contact dermatitis to Piperamido Nitrotoluene in pharmaceutical workers: A case series.

BACKGROUND: Imatinib mesylate is a first-generation tyrosine kinase inhibitor. Piperamido Nitrotoluene, also known as F5, is an intermediate used in the manufacturing of imatinib. We present a case series of allergic contact dermatitis to F5 in pharmaceutical workers. METHODS: Four male pharmaceutical workers were referred between 2007 and 2021 with new dermatitis predominantly affecting the periorbital region. All were involved in the production of imatinib and particularly exposed to F5. Following medical history and examination, they underwent patch testing to standard series and F5 diluted in white soft paraffin (WSP). RESULTS: All patients tested positive confirming a diagnosis of contact allergy to F5. The first case tested positive to F5 diluted to 1% in WSP, the second to F5 diluted to 10% in WSP and the third and fourth to F5 diluted to 1% and 10% in WSP. In all four cases, dermatitis resolved when they were removed from exposure to F5. CONCLUSIONS: To the best of our knowledge, these are the first cases of allergic contact dermatitis to F5 confirmed by patch testing in the literature. In February 2016, a generic formulation of imatinib entered the market. Globalized production of imatinib may result in further cases presenting to dermatology departments worldwide.

Pembrolizumab-associated erythema nodosum in the treatment of metastatic melanoma.

A 66-year-old woman receiving pembrolizumab for metastatic melanoma presented with tender red nodules on her shins and forearms. Biopsy was consistent with erythema nodosum (EN). The eruption responded to oral minocycline and potent topical steroids. Subsequent investigations detected bihilar lymphadenopathy, biopsied as granulomatous lymphadenitis, confirming the diagnosis of pembrolizumab-associated sarcoidosis. Pembrolizumab was stopped for two cycles and was restarted without recrudescence of EN or bihilar lymphadenopathy. Immunotherapy-associated sarcoidosis is a rare but recognized adverse event related to therapy with immune checkpoint inhibitors. EN is an uncommon manifestation of immunotherapy-induced sarcoidosis. New-onset bihilar lymphadenopathy in the context of immunotherapy requires prompt histological evaluation to differentiate between immunotherapy-associated sarcoidosis and metastatic progression. We review the literature related to immunotherapy-associated EN.

Pembrolizumab (trade name Keytruda^®) is a type of immune therapy that stimulates the body's immune system to fight cancer cells. This immune therapy can cause a variety of rashes. In this article, we describe a patient who developed a red lumpy rash on her limbs that is not commonly described with pembrolizumab. A woman was diagnosed with advanced melanoma and was treated with pembrolizumab. She developed a red lumpy rash on her arms and legs, and a biopsy showed signs of a condition called erythema nodosum. Treatment with an antibiotic tablet and strong steroid ointment were helpful. Scans of her chest showed signs of sarcoidosis in her lungs, which can be associated with erythema nodosum. Pembrolizumab was stopped, and both the rash and lung sarcoidosis stayed away when it was restarted. This type of rash has rarely been described with this kind of immune therapy, and it can be a sign of lung involvement.

Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut.

Certain therapeutic microbes, including Bifidobacteria infantis (B. infantis) 35624 exert beneficial immunoregulatory effects by mimicking commensal-immune interactions; however, the value of these effects in patients with non-gastrointestinal inflammatory conditions remains unclear. In this study, we assessed the impact of oral administration of B. infantis 35624, for 6‒8 weeks on inflammatory biomarker and plasma cytokine levels in patients with ulcerative colitis (UC) (n = 22), chronic fatigue syndrome (CFS) (n = 48) and psoriasis (n = 26) in three separate randomized, double-blind, placebo-controlled interventions. Additionally, the effect of B. infantis 35624 on immunological biomarkers in healthy subjects (n = 22) was assessed. At baseline, both gastrointestinal (UC) and non-gastrointestinal (CFS and psoriasis) patients had significantly increased plasma levels of C-reactive protein (CRP) and the pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) compared with healthy volunteers. B. infantis 35624 feeding resulted in reduced plasma CRP levels in all three inflammatory disorders compared with placebo. Interestingly, plasma TNF-α was reduced in CFS and psoriasis while IL-6 was reduced in UC and CFS. Furthermore, in healthy subjects, LPS-stimulated TNF-α and IL-6 secretion by peripheral blood mononuclear cells (PBMCs) was significantly reduced in the B. infantis 35624-treated groups compared with placebo following eight weeks of feeding. These results demonstrate the ability of this microbe to reduce systemic pro-inflammatory biomarkers in both gastrointestinal and non-gastrointestinal conditions. In conclusion, these data show that the immunomodulatory effects of the microbiota in humans are not limited to the mucosal immune system but extend to the systemic immune system.

Sodium metabisulfite--a marker for cosmetic allergy?

A 45-year-old woman developed dermatitis of the face after she applied a cosmetic package comprising day and night creams. Patch tests were performed with the British Contact Dermatitis Society (BCDS) standard, bases + preservatives, and cosmetic series in addition to samples of both creams and the individual constituents. She had positive tests to both cosmetic creams, sodium sulfite from the manufacturer's samples (5% white soft paraffin (WSP)), and sodium metabisulfite (1% pet) in our bases + preservatives battery. Sodium sulfite is a constituent of both cosmetic creams. We assume that the positive test to sodium metabisulfite is a cross-reaction. We hypothesize that a reaction to sodium metabisulfite may be a marker for sulfite allergy in cosmetics and might account for some of the unexplained positives in previous reports.