Hepascore predicts liver outcomes and all-cause mortality in long-term methotrexate users: A retrospective cohort study.

BACKGROUND AND AIM: Methotrexate (MTX) is routinely used for immunological disorders, and its long-term use is associated with hepatotoxicity. The aim of this study was to investigate whether a serum liver fibrosis test (Hepascore) predicted the risk of adverse liver-related outcomes and mortality. METHODS: A total of 92 patients in Western Australia who had a long-term MTX intake history,from 2004 to 2016, were recruited and followed up from the first Hepascore to death or end of the study. Clinical data, all deaths, and liver-related outcomes (liver-related death and decompensation) were obtained from hospital, PathWest, and WA Data Linkage Unit databases. RESULTS: Nine deaths and four adverse liver-related outcomes occurred during the follow up of 354 person-years. The 5-year survival was 86.1%. The liver-related outcome free survival was 95.6%. Baseline Hepascore ≥0.84 was associated with advanced fibrosis on liver biopsy (P = 0.025). A baseline Hepascore ≥0.84 was significantly associated with higher risks for adverse liver-related outcomes (P < 0.001) and all-cause mortality (P = 0.001). Cox regression demonstrated that only baseline Hepascore ≥0.84 was independently associated with the increased risk of all-cause mortality (7.91 [1.52-41.29], P = 0.014). Moreover, any Hepascore ≥0.84 found during follow up was independently associated with the increased risk of all-cause mortality (86.18 [4.03-1844.83], P = 0.007). CONCLUSIONS: This study demonstrated the potential importance of Hepascore monitoring in long-term MTX users. Patients with a Hepascore higher than 0.84 at any stage had increased mortality, but further studies are required to confirm this finding.

Diversity of XMEN Disease: Description of 2 Novel Variants and Analysis of the Lymphocyte Phenotype.

Variants in MAGT1 have been identified as the cause of an immune deficiency termed X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection and neoplasia (XMEN) disease. Here, we describe 2 cases of XMEN disease due to novel mutations in MAGT1, one of whom presented with classical features of XMEN disease and another who presented with a novel phenotype including probable CNS vasculitis, HHV-8 negative multicentric Castelman disease and severe molluscum contagiosum, thus highlighting the clinical diversity that may be seen in this condition. Peripheral blood immunophenotyping of these 2 patients, together with an additional 4 XMEN patients, revealed reduced NKG2D expression, impaired CD28 expression on CD8+ T cells, CD4+ T cell lymphopenia, an inverted CD4:CD8 ratio and decreased memory B cells. In addition, we showed for the first time alterations to the CD8+ T cell memory compartment, reduced CD56hi NK cells, MAIT and iNKT cells, as well as compromised differentiation of naïve CD4+ T cells into IL-21-producing Tfh-type cells in vitro. Both patients were treated with supplemental magnesium with limited benefit. However, one patient has undergone allogeneic haematopoietic stem cell transplant, with full donor chimerism and immune reconstitution. These results expand our understanding of the clinical and immunological phenotype in XMEN disease, adding to the current literature, which we further discuss here.

Colchicine in dermatology: A review.

Colchicine is an anti-inflammatory agent that has been used for decades for the treatment of various diseases including gout, familial Mediterranean fever and pericarditis and in recent years for dermatological indications including chronic urticaria, cutaneous vasculitis and psoriasis. Despite its efficacy in various cutaneous diseases, the use of colchicine may be limited by concerns over its side-effects and the potential for toxicity. This article reviews the current literature on the pharmacology of colchicine and its clinical applications in dermatology.

Cyclophosphamide in dermatology.

Cyclophosphamide is a chemotherapeutic agent which was first discovered in experimental tumours in rats, and it has since been widely used to treat malignancies and severe manifestations of various auto-immune diseases. High-dose chemotherapy and continuous daily oral regimens are associated with significant toxicity profiles, but i.v. pulsed regimens have lowered the rates of adverse effects in rheumatological studies. Cyclophosphamide has been shown to be useful in the treatment of severe autoimmune conditions due to its powerful immunosuppressive ability; however, it remains a relatively underused modality in dermatology. This article reviews the current literature on cyclophosphamide and its clinical applications in dermatology.

Drug-induced dermatomyositis after zoledronic acid.

A 57-year-old woman with prior exposure to bisphosphonates developed myalgia, proximal muscle weakness and lichenoid rash over the upper extremities and face 3 days after infusion of zoledronic acid for the management of osteoporosis. The diagnosis of dermatomyositis was made on the basis of clinical, laboratory and histological findings. This is the first report of drug-induced dermatomyositis secondary to zoledronic acid.

Cutaneous intravascular anaplastic large T-cell lymphoma: a case report and review of the literature.

Intravascular lymphoma (IVL) is a rare subtype of extranodal lymphoma. In the 2008 WHO classification of tumors of the hematopoietic and lymphoid tissues intravascular large B-cell lymphoma is included as a distinct entity. IVL of T-cell type is not included as a diagnostic category and is only mentioned in passing by Nakamura et al. as "a different entity" in their discussion of intravascular large B-cell lymphoma. T-cell IVL is rare, the majority of cases being of natural killer/T-cell phenotype. Exceptionally rare is primary cutaneous intravascular anaplastic large T-cell lymphoma. We present such a case in an otherwise well 39-year-old female having disease limited to the skin established after detailed staging investigations. This is only the third such case described in the literature. We report the clinicopathological features of this case and also review previously documented cases of cutaneous intravascular anaplastic large cell lymphoma.

Bowel bypass syndrome/bowel-associated dermatosis arthritis syndrome post laparoscopic gastric bypass surgery.

Bowel bypass syndrome, also known as bowel-associated dermatitis arthritis syndrome, has been described after a range of intestinal bypass procedures. With the increasing trend in laparoscopic gastric bypass surgery, we report an interesting case of bowel-associated dermatitis arthritis syndrome that developed 12 months following this procedure. A 49-year-old woman presented with ulcerating lesions and pustules on the upper and lower limbs, polyarthralgia, fevers and joint effusions. Before the development of these symptoms she was well, with no significant past medical or family history. A skin biopsy taken from the left shin showed superficial to mid-dermal neutrophilic dermatosis, consistent with bowel-associated dermatitis arthritis syndrome. The patient received corticosteroids, antibiotics and colchicine treatment, with control of disease after continuing with colchicine. This case may illustrate another possible complication following bariatric surgery. The significant time period between the initial surgery and the development of bowel-associated dermatitis arthritis syndrome may mean that more cases of this condition will continue to emerge.

Nephrogenic systemic fibrosis associated with liver transplantation, renal failure and gadolinium.

A 47-year-old man underwent liver transplantation for cirrhosis secondary to hepatitis C and alcoholism. This was complicated by primary donor liver dysfunction and acute renal failure requiring dialysis. Gadolinium magnetic resonance cholangiopancreatography was performed 2 weeks post transplant, and a second successful liver transplant was performed 1 week later. Shortly after this, the patient developed rapidly progressive erythematous plaques over his abdomen, lower and upper limbs. There was marked oedema and skin induration. Fibrosis severely limited his mobility, leaving him wheelchair-bound. An abdominal plaque biopsy revealed increased dermal mucin and cellularity, with proliferation of spindled fibroblastic cells. Paraprotein was not detected in the serum. Facial sparing, the absence of serum paraprotein and the histopathological findings confirmed the diagnosis of nephrogenic systemic fibrosis. Immunohistochemical stains revealed CD34-positive spindle-shaped cells, and electron microscopy did not detect free gadolinium. Following improvement in renal function and various treatments, his plaques softened, fibrosis slowed and mobility partially improved. Gadolinium magnetic resonance cholangiopancreatography was performed following this improvement. Six weeks later, further progression of nephrogenic systemic fibrosis occurred despite normal renal function.

Treatment of severe recalcitrant plaque psoriasis with single-dose intravenous tumour necrosis factor-alpha antibody (infliximab).

Infliximab is a chimeric anti-tumour necrosis factor-alpha antibody that has been demonstrated to have marked efficacy in the treatment of psoriasis. Seven patients with chronic plaque psoriasis were treated with single-dose intravenous infliximab (5 mg/kg), and the Psoriasis Area and Severity Index (PASI) and Dermatology Life Questionnaire Index (DLQI) were used as a measure of treatment efficacy. There was an average improvement in PASI scores of 69% at 2 weeks post infusion. There was an improvement in DLQI of 61%. Four of the seven patients were also seen at 10 weeks post infusion and the improvement in PASI and DLQI was sustained. All patients tolerated the initial infusion well without adverse events. The results indicate that single-dose infliximab is an effective and efficacious therapy for recalcitrant psoriasis and has a prolonged therapeutic effect.

Anogenital and buttock ulceration in infancy.

Rashes in the anogenital and buttock region are some of the commonest dermatological problems occurring in infancy. The most frequent causes seen in clinical practice are ulcerating haemangiomas, bullous impetigo and severe irritant contact dermatitis. Other causes include nutritional deficiencies, bullous diseases, trauma, Langerhans cell histiocytoses and inflammatory disorders such as pyoderma gangrenosum and Crohn's disease. This review presents a brief overview of these causes and outlines the recommended management strategies.