Vasculitis in a patient with mevalonate kinase deficiency (MKD): a case report

Background Mevalonate kinase deficiency (MKD) is a rare autoinflammatory condition caused by biallelic loss-of-function (LOF) mutations in mevalonate kinase (MVK) gene encoding the enzyme mevalonate kinase. Patients with MKD display a variety of non-specific clinical manifestations, which can lead to diagnostic delay. We report the case of a child presenting with vasculitis that was found by genetic testing to be caused by MKD, and now add this autoinflammatory disease to the ever-expanding list of causes of monogenic vasculitides. Case presentation A 2-year-old male presented with an acute 7-day history of high-grade fever, abdominal pain, diarrhoea, rectal bleeding and extensive purpuric and necrotic lesions, predominantly affecting the lower limbs. He had been suffering from recurrent episodes of fever from early in infancy, associated with maculopapular/petechial rashes triggered by intercurrent infection, and after vaccines. Extensive infection screen was negative. Skin biopsy revealed small vessel vasculitis. Visceral digital subtraction arteriography was normal. With a diagnosis of severe idiopathic cutaneous vasculitis, he was treated with corticosteroids and mycophenolate mofetil. Despite that his acute phase reactants remained elevated, fever persisted and the vasculitic lesions progressed. Next-generation sequencing revealed compound heterozygous mutation in MVK c.928G > A (p.V310M) and c.1129G > A (p.V377I) while reduced mevalonate enzyme activity was confirmed suggesting a diagnosis of MKD as a cause of the severe vasculitis. Prompt targeted treatment with IL-1 blockade was initiated preventing escalation to more toxic vasculitis therapies and reducing unnecessary exposure to cytotoxic treatment. Conclusions Our report highlights the broad clinical phenotype of MKD that includes severe cutaneous vasculitis and emphasizes the need to consider early genetic screening for young children presenting with vasculitis to exclude a monogenic vasculitis which may be amenable to targeted treatment.

Determination of Red Blood Cell Distribution Width in Patients with Primary Cutaneous Vasculitis Compared to Systemic Vasculitis

Introduction: Red blood cell distribution width (RDW) has been considered as an inflammatory marker in various disorders. Evaluation of RDW value can also be used as a novel and additional marker for differentiating systemic vasculitis from primary cutaneous vasculitis. Objective: To compare RDW value between patients with cutaneous vasculitis with systemic vasculitis, thereafter to find out it's role as an effective indicator to distinguish both forms of vasculitis. Materials and Methods: This cross sectional observational study was conduct between from July 2016 to December 2017. Total of 48 patients were divided into primary cutaneous vasculitis and systemic vasculitis. Blood was collected in EDTA tube to measure RDW value. Patient’s disease activity also scored and plotted according to Birmingham vasculitis activity score. Statistical analysis was performed by using SPSS. Results: Significantly high mean RDW were found in patients with systemic vasculitis compared to primary cutaneous vasculitis (15.09±0.92 vs. 13.48±1.1, p = 0.000). BVAS was significantly greater (13.93±5.10 vs. 4.87±2.69, p = < 0.001) in systemic vasculitis as well as in patients with high RDW group (11.73±5.71 vs. 5.37±3.96, p = < 0.001). Optimal RDW cut off point for differentiating systemic vasculitis from cutaneous vasculitis was 14.2 with 81.3% sensitivity and 81.2% specificity. Conclusion: Present study revealed importance of RDW monitoring along with disease activity in patients with any form of vasculitis. Systemic vasculitis had higher level of RDW. So RDW can be considered as a marker to discriminate systemic vasculitis from primary cutaneous vasculitis. Medicine Today 2021 Vol.33(2): 84-89

Revisiting the question of cutaneous vasculitis classification

Currently, there is no generally accepted terminology and classification of vasculitis and vascular cutaneous disorders. In Russia there are various approaches to the classification of cutaneous vasculitis vascular lesions are classified according to clinical signs, etiology and pathogenesis. Significant difficulties are caused by the lack of a unified terminology, clear diagnostic criteria for vasculitis and the existence of a large number of duplicate names, among which there are many eponymous terms. This issue is one of the most complex, confusing and debatable not only in dermatovenereology, but also in other disciplines. Modern principles of diagnosis of cutaneous vasculitis are based on an integrated assessment of the data of the disease history, clinical picture, laboratory and instrumental methods of examination. For standardization of definitions and diagnostic criteria, it is necessary, first of all, to adopt a unified interdisciplinary classification of vasculitis, which will be based on the etiopathogenetic principle. The applied unified classification of cutaneous vasculitis is proposed for discussion.

Drug-induced cutaneous vasculitis developing during Etanercept treatment for rheumatoid arthritis

Biological disease-modifying anti-rheumatic drugs (bDMARDs) are widely used for the treatment of chronic inflammatory rheumatic diseases. Since the introduction of tumor necrosis factor alpha (TNF-) inhibitors, the treatment of rheumatoid arthritis has been revolutionized. The approach of targeting TNF- has considerably improved the success of the treatment of rheumatoid arthritis. Their effectiveness has been extensively proven in randomized clinical trials and in clinical practice. Randomized clinical trials and post-marketing studies proved that patients undergoing TNF- inhibitors therapy are at increased risk of infectious disease, bacterial, viral, fungal, opportunistic, oncology and skin adverse effects such as psoriasis and angiitis of the skin. In this case report drug-induced cutaneous vasculitis developing during TNF- inhibitor (Etanercept) treatment for rheumatoid arthritis is described.

Immune checkpoint molecule expression is altered in the skin and peripheral blood in vasculitis

Dysfunction of immunoinhibitory signals and persistent T cell activation reportedly play important roles in the development of vasculitis. The skin is one of the most accessible organs, and it is suitable for the characterization of immune cell signatures. However, the inhibitory checkpoint molecules in the skin and their relevance to vasculitis have not been studied. Here, we investigated the profile of immune checkpoint molecules in the skin and peripheral blood of patients with vasculitis and healthy donors. We found that some of the inhibitory checkpoint molecules, including programmed cell death 1 receptor (PD-1), were elevated in T-cells in the blood of patients with systemic and cutaneous vasculitis. In addition, programmed death-ligand 1 (PD-L1) expression was elevated in the skin of patients with cutaneous vasculitis. Histologically, PD-L1 was highly expressed in the vessels in the skin along with CD4+ and CD8+ T-cell infiltration in patients with cutaneous vasculitis. Notably, plasma soluble PD-L1 levels were increased, and these correlated with C-reactive protein in patients with systemic vasculitis. Our findings suggest that inhibitory checkpoint molecules might be differentially modulated in the skin and peripheral blood of patients with vasculitis, and that the alteration of the PD-L1/PD-1 axis may be associated with the regulation of T-cell activation in vasculitis.