Benzeeta Pinto

Leflunomide-induced DRESS syndrome with renal involvement and vasculitis

DRESS or drug reaction (or rash) with eosinophilia and systemic symptoms belongs to the severe cutaneous adverse reaction group and is characterized by hematological abnormalities and visceral organ involvement. Although most often related with anticonvulsant and sulfonamide use, it is reported with numerous other drugs. We report an unusual case of DRESS syndrome due to Leflunomide, also complicated by renal involvement in the form of granulomatous interstitial nephritis and vasculitis. On a review of the literature, eight similar cases were found, and these are discussed.

Comparison of two different folic acid doses with methotrexate – a randomized controlled trial (FOLVARI Study)

IntroductionThere is reasonable evidence that folic acid 5–10 mg per week leads to reduction in methotrexate (MTX) toxicity in rheumatoid arthritis (RA). However, this is based on studies conducted with lower MTX dosage than used currently. It is unclear whether higher doses of folic acid may be better in reducing toxicity.MethodsThis was a double-blind randomized controlled trial of 24 weeks duration. To be eligible, patients should have rheumatoid arthritis (1987 American College of Rheumatology criteria), be 18–75 years of age, not be on MTX and have active disease as defined by ‘Modified Disease Activity Score using three variables’ (DAS28(3)) > 3.2. MTX was started at 10 mg/week and escalated to 25 mg/week by 12 weeks. Folic acid was given at a dose of 10 mg (FA10) or 30 mg per week (FA30). Co-primary endpoints were incidence of toxicity (undesirable symptoms and laboratory abnormalities) and change in disease activity by 24 weeks. Intention-to-treat and per-protocol analyses were performed.ResultsAmong 100 patients enrolled, 51 and 49 were randomized to FA10 and FA30 respectively. By 24 weeks, there were 6 patient withdrawals in either group and mean(±SD) dose of MTX was 22.8 ± 4.4 and 21.4 ± 4.6 mg per week (p = 0.1). Frequency of patients with undesirable symptoms was non-significantly lower by 7.4 % (95 % confidence interval −27.4 to 12.7 %) in FA10 compared to FA30. There was also no difference in frequency of transaminitis (>Upper limit of normal (ULN)) (42.6, 45.7 %, p = 0.7) or transminitis as per primary endpoint (>2xULN) (10.6, 8.7 %, p = 1.0) or cytopenias (4.3, 4.3 %, p = 0.9). There was no difference in the primary end-point of occurrence of any adverse effect (symptom or laboratory) in FA10 and FA30 (46.8, 54.3 %, p = 0.5). At 24 weeks, DAS28(3) declined in both groups by a similar extent (−1.1 ± 1.0, −1.3 ± 1.0, p = 0.2) and ‘European League Against Rheumatism’ good or moderate response occurred in 56.9 and 67.4 % (p = 0.3).ConclusionsEven with the high doses of MTX used in current practice, there was no additional benefit (or harm) of a higher dose of folic acid (30 mg/week) over a usual dose (10 mg/week).Trial RegistrationClinicaltrials.gov NCT01583959 Registered 15 March 2012

A case series and review of Poncet's disease, and the utility of current diagnostic criteria.

Poncets disease is a well recognized form of reactive arthritis in the presence of extra‐articular tuberculosis. There are very limited case reports even from countries where tuberculosis is common and there are no accepted diagnostic criteria for Poncets disease. In the present study we are describing clinical features of Poncets disease from a tuberculosis‐endemic region along with a proposal of a new diagnostic criteria.

Clinical features and long‐term outcomes of 105 granulomatosis with polyangiitis patients: A single center experience from north India

To describe the clinical features, treatment and long‐term outcomes in north Indian patients with granulomatosis with polyangiitis (GPA).

Giant cell arteritis in India: Report from a tertiary care center along with total published experience from India

OBJECTIVES Giant cell arteritis (GCA) is a granulomatous large vessel vasculitis with very scarce data from India. The purpose of this study was to present a comprehensive data of all published Indian cases along with our experience from North India. MATERIALS AND METHODS This was a retrospective study of all patients diagnosed to be having GCA according to the American College of Rheumatology criteria at a large tertiary care hospital. The demographic data, clinical, investigations, treatment details, and outcomes were noted. Details of all case series and case reports published from India were pooled along with our experience in order to generate a cumulative data of all cases from India. This was then compared with several large published case series from South America, Europe, and Asia. RESULTS A total of 72 patients (17 patients in the present series and another 55 patients from other Indian case series and case reports) were identified. The findings of our study are similar to the studies published from other parts of the world, except for the onset of the disease a decade earlier, a male predilection, a lower temporal artery biopsy positivity, and a higher incidence of ophthalmic complications. CONCLUSIONS Indian patients with GCA have an earlier age of onset, male preponderance, and higher ophthalmic complications.

Poncet's disease presenting as Pseudo‐Behçet's disease

Dear Editor, A 45-year-old man with no previous comorbidities, presented with a history of recurrent ulcer on the glans penis for 4 years, recurrent oral ulcers for 3 years, recurrent pain and swelling of both ankles for 2 years, erythematous tender nodules on both lower limbs for 4 months and red eye for 3 months. He was evaluated by multiple physicians in the last 4 years and was noted to have aphthous stomatitis, genital ulcer diagnosed as herpes genitalis and bilateral ankle arthritis. He was treated symptomatically with non-steroidal anti-inflammatory drugs (NSAIDs) for arthritis and short courses of acyclovir for the genital ulcer with some relief. He was started on sulfasalazine in 2010 which he took for 6 months. He stopped taking sulfasalazine on his own in view of non-response and did not subsequently take any other disease-modifying anti-rheumatic drugs (DMARDs) or alternative medication. He had a relapsing and remitting course with recent increase in symptoms for 4 months. On evaluation, he was found to have active synovitis in ankles, erythema nodosum (Fig. 1), redness in the left eye, pseudofolliculitis and a raised erythematous lesion on the glans (Fig. 2). X-rays of both ankle joints revealed no erosions. Hemogram, routine biochemical investigations and urine examination were within normal limits. A diagnosis of Behc et’s disease was considered in view of recurrent oral and genital ulceration. However, an ulcer on glans rather than on the shaft of the penis or scrotum and absence of scrotal scars were odd for Behcet’s disease. In view of bilateral ankle arthritis and erythema nodosum, L€ ofgren’s and Poncet’s diseases were considered in the differential diagnosis. Ulcerated phlyctenular conjunctivitis was diagnosed on slit lamp examination. Skin biopsy from erythematous lesions on the leg showed epithelioid granulomas and vasculitis consistent with papulonecrotic tuberculid (Fig. 3). Ziehl–Neelsen stain for acid fast bacilli was negative; however, polymerase chain reaction (PCR) of the skin biopsy specimen was positive for IS6110 (gene specific for Mycobacterium tuberculosis). Mantoux test was 30 9 30 mm. Contrast-enhanced computed tomography of the chest was done to look for tubercular focus which revealed a small nodular lesion in the right middle lobe which was not amenable for fine-needle apiratory cytology or biopsy. In view of the presence of papulonecrotic tuberculid with TB PCR positivity, phlyctenular conjunctivitis and a strongly positive Mantoux test in an endemic region, a diagnosis of Poncet’s disease was made and the patient was started on fourdrug antitubercular treatment with isoniazid, rifampicin, Figure 1 Active synovitis in ankles, erythema nodosum. Figure 2 Pseudofolliculitis and raised erythematous lesion on glans.

Granulomatosis with polyangiitis and severe respiratory involvement.

Granulomatosis with polyangiitis (GPA) is a small-vessel vasculitis with a predilection to involve upper and lower airways, lung, and kidney. It is characterized by a necrotizing granulomatous inflammation of the airways and lung along with vasculitis and pauci-immune glomerulonephritis. We report a case of GPA in a patient presenting in hypoxemic respiratory failure who developed an unusual complication.

Polyarteritis nodosa in north India: clinical manifestations and outcomes

There has been a significant decrease in the number of published reports of classical polyarteritis nodosa (PAN) in the post‐Chapel Hill consensus conference (CHCC) nomenclature era with only two series published from Asia. We report a case series of PAN from north India.

Antiphospholipid syndrome: A review

Antiphospholipid syndrome is being increasingly recognized as a disease with a myriad of clinical manifestations ranging from recurrent thrombosis and pregnancy morbidity to valvular lesions, transverse myelitis, thrombocytopenia and hemolytic anemia. It may be primary or secondary, i.e., associated with other autoimmune diseases. The latest classification criteria (Sydney 2006) recognize just three tests to define this syndrome-lupus anticoagulant, anticardiolipin antobodies and anti β2 glycoprotein 1 antibodies. Treatment of thrombotic events involves lifelong anticoagulation with vitamin K antagonists like warfarin. Antiphospholipid antibody syndrome (APS) with only pregnancy morbidity is treated with thromboprophylaxis using heparin during pregnancy and postpartum for 6 weeks. Catastrophic APS occurs in approximately 1% of APS, and is characterized by microvascular thrombosis (thrombotic storm) and organ dysfunction. In this review we discuss the pathogenesis, diagnosis, treatment and prognosis of the APS.

Nocardia pyomyositis in a patient with granulomatosis with polyangiitis

Dear Editor, Pyomyositis is an infection of the skeletal muscles without involvement of adjoining structures like skin, soft tissue or bone. Staphylococcus aureus is the most common etiological agent reported in all the case series and case reports. Infection with other microorganisms is uncommon, and with Nocardia is very rare, with no reports in the English literature. We are reporting one such case of Nocardia pyomyositis in a patient on immunosuppression for granulomatosis with polyangiitis (GPA). A 63-year-old man with GPA, presented with fever and left thigh pain for 3 days. He was diagnosed as having GPA 3.5 years previously, when he presented with sinusitis, nasal crusting, nasal bleeding, pulmonary nodules, microscopic hematuria, renal dysfunction (serum creatinine 1.5 mg/dL), ventricular failure, antineutrophil cytoplasmic antibodies and anti-PR3 positivity. Cyclophosphamide pulses according to the European Vasculitis Study Group regime were given initially, and he was presently on prednisolone (5 mg/day) and azathioprine (100 mg/day). He had moderate grade (up to 38.3°C) fever for 3 days, associated with severe pain in the left thigh resulting in inability to walk. There was marked local tenderness of the hamstring muscles. Further clinical examination was normal. There was mild anemia (hemoglobin 91 g/L [reference value 120–180 gm/L), total leucocyte count 6000/lL (4–11 9 10/lL), platelet count 344 9 10/lL (150– 400 9 10/lL). Serum electrolytes, renal functions and liver functions were normal. Urine routine examination was also normal. Initial ultrasound of the thigh done 2 days prior to admission was normal. MRI of the thigh region demonstrated abnormal T2 hyperintensity in muscles of the posterior and adductor compartment of the left thigh, extending to the obturator muscles, associated with collections, the largest measuring 6.5 9 4.5 cm in the muscular and intermuscular compartments of the upper thigh (Fig. 1). There were no hip joint effusions. One hundred and sixty-five microliters of frank pus was aspirated under ultrasound guidance. Pus culture grew Gram-positive branching filamentous bacilli of Nocardia species. Intravenous trimethoprim-sulfamethoxazole was given at a dose of 10 mg/kg of trimethoprim, along with amikacin 15 mg/kg, for 21 days. Repeated aspirations of the collections were required during admission, eventually resulting in clinical improvement and radiological resolution over 3 weeks. Oral trimethoprim-sulfamethoxazole was started with a plan to continue it for at least 1 year. Pyomyositis is a purulent disease condition involving skeletal muscles. Various risk factors include human immunodeficiency infection, patients on