Vikramraj K. Jain

Splenectomy increases the subsequent risk of systemic lupus erythematosus: a word of caution

This comment refers to the article available at: http://dx.doi.org/10.1007/s00296-015-3388-9 .

Comparing the efficacy of low-dose vs high-dose cyclophosphamide regimen as induction therapy in the treatment of proliferative lupus nephritis: a single center study

Cyclophosphamide (CYC) has been the backbone immunosuppressive drug to achieve sustained remission in lupus nephritis (LN). The aim was to evaluate the efficacy and compare adverse effects of low and high dose intravenous CYC therapy in Indian patients with proliferative lupus nephritis. An open-label, parallel group, randomized controlled trial involving 75 patients with class III/IV LN was conducted after obtaining informed consent. The low dose group (n = 38) received 6 × 500 mg CYC fortnightly and high dose group (n = 37) received 6 × 750 mg/m2 CYC four-weekly followed by azathioprine. The primary outcome was complete/partial/no response at 52 weeks. The secondary outcomes were renal and non-renal flares and adverse events. Intention-to-treat analyses were performed. At 52 weeks, 27 (73%) in high dose group achieved complete/partial response (CR/PR) vs 19 (50%) in low dose (p = 0.04). CR was higher in the high dose vs low dose [24 (65%) vs 17 (44%)], although not statistically significant. Non-responders (NR) in the high dose group were also significantly lower 10 (27%) vs low dose 19 (50%) (p = 0.04). The change in the SLEDAI (Median, IQR) was also higher in the high dose 16 (7–20) in contrast to the low dose 10 (5.5–14) (p = 0.04). There was significant alopecia and CYC-induced leucopenia in high dose group. Renal relapses were significantly higher in the low dose group vs high dose [9 (24%) vs 1(3%), (p = 0.01)]. At 52 weeks, high dose CYC was more effective in inducing remission with decreased renal relapses in our population.Trial Registration: The study was registered at http://www.clintrials.gov. NCT02645565.

Renal involvement in primary Sjogren’s syndrome: a prospective cohort study

The objective of the study is to prospectively evaluate the spectrum of clinical and subclinical renal involvement in patients with primary Sjogren’s syndrome (pSS). Of the 174 patients screened, seventy patients with pSS underwent renal function tests, urine examination, renal ultrasound, arterial blood gases, urine pH followed by urine acidification test and renal biopsy (if indicated). Renal tubular acidosis (RTA) was treated with alkali replacement and moderate–severe tubulointerstitial nephritis (TIN) was treated with oral prednisolone. Sixty-two patients completed 1-year follow-up. A comparison was made between patients with and without renal involvement. Thirty-five (50%) patients had renal involvement. They had a lower baseline eGFR (71.85 ± 18.04 vs. 83.8 ± 17, p = 0.005). Twenty-nine patients had RTA (25 complete and 4 incomplete). Eleven patients had urinary abnormalities. Patients with RTA (n = 29) were younger (34.9 ± 9 vs. 42 ± 11.3, p = 0.006), had fewer articular (34% vs. 78%, p = 0.001) and ocular sicca (62% vs. 88%, P = 0.01) than those without RTA (n = 41) and commonly presented with hypokalemic paralysis. On biopsy, TIN (9/17) and IgA nephropathy (3/17) were most common. On follow-up, there was no clinically significant change in eGFR; however, one patient with renal calculi and incomplete distal renal tubular acidosis (dRTA) progressed to complete dRTA. Two patients treated with steroids had marginal improvement in eGFR. Renal involvement in pSS is under-recognized with the most common manifestation being RTA presenting with hypokalemic paralysis. These patients are younger with less articular and sicca symptoms. Subclinical RTA may progress to complete RTA. Renal biopsy should be considered in all patients with renal involvement.

Tuberculosis mimicking primary systemic vasculitis: not to be missed!

Infections are an important differential diagnosis in patients presenting with features of systemic vasculitis. We report a young lady with constitutional features, leg ulcers, digital gangrene and absent peripheral pulses with cervical adenopathy. Chest imaging revealed multiple necrotic lung lesions and involvement of left subclavian artery at its origin from the aorta, Histopathology from cervical lymph nodes showed multiple caseated lymph nodes, which in the context of a positive Mantoux test led us to diagnose tuberculosis and institute appropriate therapy. This is only the second report of tuberculosis presenting as peripheral gangrene, cutaneous ulcers and absent pulses, and serves to educate rheumatologists regarding the need to consider infections as mimics of vasculitis, especially in the developing countries.

Inflammatory rheumatic diseases in the elderly

Rapid aging of worlds population will translate into more elderly patients in the near future. Diagnosis of inflammatory rheumatic diseases in this age group is complicated by atypical clinical features compared to the younger onset group, nonspecific positivity of serological parameters, and confounding radiological signs. Management of these diseases also presents unique challenges in lieu of altered physiology of elderly, cognitive decline, presence of comorbidities, and altered immune system (inflammaging). Hence, this review attempts to synthesize the existing knowledge of the clinical, diagnostic, and therapeutic idiosyncrasies of inflammatory rheumatic diseases in this subgroup of population.

AB0335 Assessment of Adrenal Reserve in Patients with Rheumatoid Arthritis

Background The hypothalamic-pituitary-adrenal (HPA) axis plays an important role in regulating immune responses. Deficiency in HPA function might contribute to pathogenesis and persistence of rheumatoid arthritis (RA) (1,2). Previous steroid use may also be an important cause for HPA insufficiency as abrupt withdrawal may lead to precipitation of adrenal insufficiency. Therefore, there is a need to assess the functional status of HPA axis to aid the management of patients. Objectives To assess adrenal functions (reserve) in patients with rheumatoid arthritis and to identify the factors associated with it. Methods Low dose ACTH (1μg) stimulation test was performed for 137 RA patients and blood samples were collected after 30 minutes for cortisol response. Serum cortisol of >18 μg/ml was considered as normal response (3). Presence of adrenal insufficiency was analyzed for possible association with age of onset, sex, duration, previous steroid use, RF, Anti-cyclic citrullinated peptide antibodies (ACPA), VAS, HAQ-Indian and DAS28 using SPSS v.17 software (IBM, India). Results Thirty one (22.7%) patients were found to have adrenal insufficiency. Patients with adrenal insufficiency had significantly higher (p<0.05) DAS 28 & ACPA titers. On logistic regression ESR and tender Joint count (TJ) were found to be significantly associated with adrenal insufficiency. However, there was no association was found for sex group, age of onset, duration, auto-antibody profile, extra-articular manifestations, hsCRP, DAS 28, treatment with DMARDs and previous steroid use (>3 month back). Conclusions Significant number of patients with rheumatoid arthritis had adrenal insufficiency, which was higher in patients with active disease. It emphasizes the concept of relative adrenal insufficiency in RA (4,5). and necessitates further evaluation in a larger cohort to find other associations like inflammatory cytokines or genetics and to explore the cause or effect relationship between RA and adrenal insufficiency. References Cutolo M, Foppiani L, Minuto F. Hypothalamic-pituitary-adrenal axis impairment in the pathogenesis of rheumatoid arthritis and polymyalgia rheumatica. J Endocrinol Invest. 2002;25(10 Suppl):19–23. Straub RH, Paimela L, Peltomaa R, Schölmerich J, Leirisalo-Repo M. Inadequately low serum levels of steroid hormones in relation to interleukin-6 and tumor necrosis factor in untreated patients with early rheumatoid arthritis and reactive arthritis. Arthritis Rheum. 2002 Mar;46(3):654–62. Crowley S, Hindmarsh PC, Holownia P, Honour JW, Brook CG. The use of low doses of ACTH in the investigation of adrenal function in man. J Endocrinol. 1991 Sep;130(3):475–9. Masi AT, Aldag JC, Jacobs JWG. Rheumatoid arthritis: neuroendocrine immune integrated physiopathogenetic perspectives and therapy. Rheum Dis Clin North Am. 2005 Feb;31(1):131–60, x. Gudbjörnsson B, Skogseid B, Oberg K, Wide L, Hällgren R. Intact adrenocorticotropic hormone secretion but impaired cortisol response in patients with active rheumatoid arthritis. Effect of glucocorticoids. J Rheumatol. 1996 Apr;23(4):596–602. Disclosure of Interest None declared

AB0559 Hypokalemic Paralysis in Primary Sjogren Syndrome: is IT A Distinct Clinical Subset Which Requires Lifelong Potassium Supplementation Rather than Immunosuppressants?

Background Primary Sjögrens syndrome (pSS) is a systemic autoimmune disorder with predominant involvement of exocrine glands in middle aged females. It may involve extra-glandular tissues such as lung, liver, kidney, pancreas, skin, and central nervous system. Clinically significant renal involvement in pSS is rare and interstitial nephritis is the commonest histopathological finding1. The resulting tubular defects may present with failure to concentrate urine (hyposthenuria) and type I (distal) renal tubular acidosis characterized by hyperchloremic metabolic acidosis and hypokalemia. We describe a series of 15 cases of pSS who presented with hypokalemic periodic paralysis as the initial manifestation. Their clinical features; biochemical and immunological parameters are compared and contrasted with those without hypokalemic weakness. Objectives To explore the clinical, biochemical, serologic features, and therapeutic responses in Primary Sjogrens syndrome (pSS) patients who presented with hypokalemic paralysis as the initial manifestation. Methods Sixty patients of pSS (diagnosis based on modified European-American classification criteria) are on our follow up from November 2009 to August 2012. A few of these patients were diagnosed following admission to emergency services with hypokalemic paralysis. They were compared for differences in clinical features, biochemistry and serological parameters with pSS patients without hypokalemic paralysis. Results Symptomatic hypokalemia was the presenting symptom in 15 out of 60 (25%) primary SS. All patients in the hypokalemic paralysis group were females and with a lower age of onset (27.8±8.3 vs 38.85±11.5 yrs). Six of 15 (40%) patients did not have the classical sicca symptoms. All patients with hypokalemic paralysis had biochemical features of distal renal tubular acidosis and high titers of anti SSA antibody. During a mean follow up of sixteen months, only two patient developed relapse of hypokalemic weakness following stoppage of potassium supplements. Conclusions There exists a distinct subset of pSS who present with onset at younger age, distal RTA, hypokalemic paralysis and high titres of anti SSA antibody sometimes even without characteristic exocrinopathy. Genetic analysis may help in further characterization of these patients. Therefore, all young females presenting with hypokalemic paralysis should be investigated for underlying pSS. References Andreas V. Goules, Ioanna P. Tatouli, Haralampos M. Moutsopoulos, Athanasios G. Tzioufas. Clinically Significant Renal Involvement in Primary Sjögrens Syndrome. Clinical Presentation and Outcome. Arthritis & Rheumatism.2013 Nov;65(11):2945–53 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1739