VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) for the dermatologist.

In 2020, Beck et al1 described a novel adult autoinflammatory syndrome entitled VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic), a newly-discovered disorder that connected previously unrelated inflammatory syndromes and a prototype for a new class of hematoinflammatory diseases.2 Eighty-nine percent of published cases have documented skin involvement, but despite the high incidence and diagnostic accessibility of skin manifestations, there has been little focus on the dermatological features of VEXAS syndrome thus far. A PubMed search of all published case reports of VEXAS syndrome to date was performed, with inclusion of all cases confirmed by genetic sequencing, and this review summarizes the reported dermatological signs. There have already been 141 confirmed published cases since original publication, 126 of which had documented cutaneous signs.1-34 A wide range of skin presentations are reported, including Sweet-like urticated and tender erythematous nodules, cartilaginous involvement with chondritis, cutaneous vasculitis, and periorbital angiodema.1-34 Many patients had been diagnosed with Sweet syndrome, relapsing polychondritis, polyarteritis nodosa, or erythema nodosum.1-34 Hallmarks of skin histopathology are a neutrophilic dermatosis with coexisting or exclusive leukocytoclastic vasculitis.1 The new classification therefore helps link previously disparate inflammatory skin conditions into a unifying pathophysiological pathway.

Challenges of aciclovir-resistant HSV infection in allogeneic bone marrow transplant recipients.

INTRODUCTION: The emergence of herpes simplex virus (HSV) resistance to aciclovir (ACV) has increasingly been reported among hematopoietic stem cell transplant (HSCT) recipients and often associated with extended ACV prophylaxis. METHODS: Between June 2011 and June 2019, medical records of 532 HSCT recipients with suspected HSV infection were retrospectively analyzed. HSV-1 and HSV-2 positive samples were identified in 47 and 16 patients respectively. Analysis of HSV resistance to antivirals was performed at the Public Health England reference laboratory in London using phenotypic and/or genotypic resistance assays. RESULTS: The prevalence of ACV-resistant HSV accounted for 17% (8/48) of infected HSV-1 cases. All 8 patients received T-cell depleted allogeneic HSCT for hematological malignancies. Half of these patients were male with a median age was 57.5 years (range; 26-63). Chronic Graft versus Host disease (cGVHD) affected 7 patients before HSV-1 diagnosis. HSV-1 infection developed while receiving either intravenous ACV (n = 2) or oral ACV (n = 6 patients) prophylaxis at a median of 373 [range,18-2183] days post-HSCT. ACV resistance was clinically suspected at a median of 25 [range,16-109] days after initial HSV diagnosis and subsequently laboratory confirmed at a median of 25 (range,10-59) days. All patients presented with hemorrhagic oral mucositis refractory to treatment dose ACV. Foscarnet (FOS) treatment was initiated in all 8 patients (pending laboratory confirmation of ACV resistance) with some effect but associated with significant toxicity burden. Four patients presented again with recurrent HSV infection or no resolution. Three with recurrent HSV died from other causes while suffering from persistent oral HSV lesions. CONCLUSION: A prolonged immunosuppressed state following T-deplete HSCTs alongside extended use of ACV, early onset systemic HSV infection, presence of cGVHD, and treatment toxicities pose a significant challenge to the management of ACV resistant HSV infections and alternative effective antiviral options remains an unmet need in this clinical setting.

Intractable pruritus in chronic myelomonocytic leukaemia and myelodysplastic syndromes: a case series.

Intractable pruritus without visible primary skin lesions and refractory to antihistamines as a primary presentation of chronic myelomonocytic leukaemia (CMML) and myelodysplastic syndrome (MDS) is not well recognised. We present two cases of CMML and two cases of MDS with this challenging symptom. In two of them, the pruritus preceded the diagnosis of MDS/CMML by months. Various chemotherapeutic and immunosuppressive options were used with variable success. In one of the cases, the pruritus persisted despite achieving morphological remission of CMML with azacitidine but had a remarkable complete response to cladribine. The pathogenesis of intractable itching in CMML and MDS remains unclear but seems to be linked to the biology of these diseases and could precede definitive diagnostic features. Earlier diagnosis of these myeloid disorders may therefore be aided by increasing awareness among clinicians of the association with pruritus.

Composite biomarker panel for prediction of severity and diagnosis of acute GVHD with T-cell-depleted allogeneic stem cell transplants-single centre pilot study.

AIMS: Acute graft-versus-host disease (aGVHD) is a leading cause of morbidity and mortality following allogeneic haematopoietic stem cell transplantation (HSCT). The aim of this study was to evaluate the clinical utility of a composite biomarker panel to help identify individuals at risk of developing aGVHD, and to help predict and differentiate between severity of aGVHD following T-cell-depleted allogeneic HSCT. METHODS: We retrospectively analysed our cohort of biopsy confirmed patients with aGVHD, who underwent T-cell-depleted HSCT and matched them with negative controls without any evidence of aGVHD. Post-transplant serum samples on days 0 and 7 and at onset of aGVHD were analysed for elafin, regenerating islet-derived 3-α, soluble tumour necrosis factor receptor-1, soluble interleukin-2 receptor-α and hepatocyte growth factor. Biomarker data were combined as composite panels A-F (table 2) using logistic regression analysis. Receiver operating characteristic analysis was performed to study sensitivity and specificity of the composite panels. RESULTS: Our composite biomarker panels significantly differentiated between aGVHD and no GVHD patients at time of onset (panel E) and reliably predicted severity of GVHD grades at days 0 and 7 post-transplant (panels B and D). The area under the curve for the composite panel at time of onset was 0.65 with specificity, sensitivity, positive and negative predictive values of 100%, 55.6%, 100% and 78.9%, respectively (p=0.03). CONCLUSIONS: This pilot data support the usefulness of these composite biomarker panels in the prediction of severity and diagnosis of aGVHD in patients undergoing T-cell-depleted reduced intensity allogeneic HSCT.