Sathish Kumar

Rapid control of disease activity by tocilizumab in 10 ‘difficult-to-treat’ cases of Takayasu arteritis

To assess outcome of 10 ‘difficult to treat’ patients with Takayasu arteritis (TA) treated with tocilizumab.

Unusual presentation of childhood Systemic Lupus Erythematosus

Bullous systemic lupus erythematosus is a rare blistering condition with a distinctive combination of clinical, histological and immunopathologic features that together constitute a unique bullous disease phenotype. It is often associated with autoimmunity to type VII collagen. Here we report a child who presented with bullous systemic lupus erythematosus. Rapid resolution of the blisters occurred following treatment with dapsone.

Childhood-onset Takayasu arteritis: an update.

Childhood‐onset Takayasu arteritis (c‐TA) is a distinct subset affecting a wide age group, ranging from young infants to adolescents and it differs from adult TA in many aspects. There is scarcity of data on c‐TA worldwide. The disease is classified using the European League Against Rheumatism/Pediatric Rheumatology International Trials Organization/Pediatric Rheumatology European Society criteria. The non‐specific nature of presenting complaints and lack of appropriate biomarkers delay the early diagnosis of this illness and many children present with complications, which become irreversible once they set in. One of the largest cohorts of 40 children with c‐TA from our center reports hypertension as the commonest presenting feature. Systemic symptoms like headache, fever and weight loss are also described. Assessment of disease in c‐TA is done by correlating clinical features with raised inflammatory markers. Advanced imaging plays an important role in diagnosis. In c‐TA, the role of magnetic resonance angiography is advocated, taking into consideration the enormous amount of radiation exposure with other modalities. Complications of c‐TA include cardiovascular, pulmonary, neurological and those arising secondary to long‐term steroid and immunosuppression therapy.

A descriptive analysis of 14 cases of progressive-psuedorheumatoid-arthropathy of childhood from south India: Review of literature in comparison with Juvenile Idiopathic Arthritis

BACKGROUND Progressive-psuedorheumatoid-arthropathy of childhood (PPAC) is an autosomal recessive single gene skeletal dysplasia involving joints. The gene attributed to its cause is WNT1-inducible-signaling pathway protein3 (WISP3). OBJECTIVE To study the clinical and radiographic presentation of PPAC in Indian patients and to compare with described features of PPAC and Juvenile Idiopathic Arthritis (JIA) from published literature. METHODS All cases (n = 14) of PPAC seen in the Rheumatology and Clinical Genetics outpatient clinic between 2008 and 2011 with classical, clinical, and radiological features were studied. The demographic and clinical data were obtained from medical records of the outpatient visits. RESULTS Slight female preponderance (57%) and history of consanguinity in parents (43%) was observed in this group. The median age at onset was 4.5 years (range from birth to 9 years of age). Early presentation below the age of 3 years was seen in 3/14 patients (21%) in this group. The growth of all the patients fell below the 3rd percentile for the age. Historically, hip joint involvement was the most common presenting feature; however, elbow, wrist, knees, feet, spine, shoulder joints and small joints, namely proximal interphalangeal (PIP), distal interphalangeal (DIP), metacarpophalangeal (MCP), metatarsophalangeal joints (MTP), and interphalangeal joints (IP) of the feet, were also involved, either clinically or radiologically in varying proportions. Platyspondyly was noted in all. Molecular analysis of the WISP3 gene identified mutations in all the 5 individuals in whom it was done. CONCLUSION This descriptive case series of PPAC from India reports distinctly differentiating clinical, radiological, and molecular markers in contrast with classically described features of JIA, its mimic. Early presentation (age of onset below 3 years) with involvement of interphalangeal joints seen in three patients (21%) was a unique finding, with missense WISP3 gene mutations in all of them. Timely diagnosis of this entity can spare the patient from unnecessary investigations and toxic medications.

Posterior reversible encephalopathy syndrome in a child with autoimmune lymphoproliferative syndrome: Case report and review of literature

Posterior reversible encephalopathy syndrome (PRES) is characterized by headache, nausea, vomiting, seizures and visual disturbances. PRES has been usually associated with hypertension, chronic renal disease, malignancy and chemotherapeutic agents. We report the association of PRES with Autoimmune lymphoproliferative syndrome, which to our best knowledge has not been reported before.

Long-term outcome of 251 patients with Takayasu arteritis on combination immunosuppressant therapy:: Single centre experience from a large tertiary care teaching hospital in Southern India

INTRODUCTION Long-term outcome studies in Takayasu arteritis (TA) are few and limited by small sample size. In this study, we analysed the outcome of treatment in a large series of TA patients with a minimum follow-up period of ≥12 months by objective instruments. MATERIALS AND METHODS Patients with TA satisfying the 1990 ACR, Ishikawas, Sharmas or EULAR/PRESS criteria were recruited from our clinics between 1998 and 2016. Only patients with a minimum follow up of 12 months were studied. Data related to clinical presentation, disease extent (DEI.Tak score), activity [Indian Takayasu arteritis clinical activity score, that is, ITAS-A (CRP)] and damage score [Takayasu arteritis damage score (TADS)], angiography and treatment were collected for all patients. Response to treatment was categorised as complete response (CR), partial response (PR) or refractory disease. Patients with sustained CR on prednisolone dose of ≤5mg/day were classified as having sustained inactive disease. Appropriate statistical tests were used for parametric and non-parametric data. Relapse free survival was projected by Kaplan-Meir curve. Cox proportional hazards regression plot was used to compare the efficacy of medications. Predictors of sustained response were identified by logistic regression and a prediction model was constructed. RESULTS Among 503 TA patients examined during study period, 251 had follow-up of ≥12 months and were included in this study. Median follow-up duration was 42 months (IQR: 24-81, maximum 240 months). Patients (81.7% females, mean age of 29.2 ± 11.8 years, symptom duration of 24 [6-70] months) were treated by a uniform protocol that included high dose steroids (n = 239) plus concurrent steroid-sparing immunosuppressant (n = 235) with mycophenolate in majority. Biological agents (n = 44 patients) and revascularisation procedures were used in symptomatic patients after control of disease activity. At 1st follow-up, CR (ITAS2010 = 0, CRP < 6mg/L and non-progressive disease on angiography) was observed in 173 (68.9%), partial response (PR) in 42 (16.7%) and no response was seen in only 36 (14%) patients. CR was sustained till the last follow up in 116 (65.9%) of 173 patients with initial CR, while 87 (49.4%) of them achieved sustained inactive disease. Disease activity relapsed at a median duration of 37 (29.9-44.1) months in 56 patients. Cumulative relapse free survival was 93%, 73%, 66% and 52% at 1, 3, 5 and 10 years, respectively. Baseline CRP < 6.2, DEI.Tak < 9 and angiographic type 4 disease predicted sustained inactive disease and a model comprising these parameters showed sensitivity and specificity of 70% and 61.1%. Two fatalities were observed. New vascular lesions during follow up were observed in 50 (19.9%) patients. Overall, 92.8% had at least one period of CR or PR while 7.2% were refractory to treatment till the last follow up. Damage progression (∆TADS > 1) was arrested in 68% of patients and was lower in patients with sustained inactive disease [0 (0-1)] as compared to the rest [1 (0-2.75)], p = 0.000. Both early response as well as cumulative hazard for relapse were similar between patients initiated on 0.5 and 1mg/kg/day steroids. CONCLUSIONS Our strategy of upfront combination immunosuppressant therapy stabilised disease activity in 92.8% of patients, while 7.2% had true refractory disease. Relapse free survival was 66% at 5 years and 52% at 10 years. Damage progression was arrested in 68% and only 2 fatalities were observed. Initial steroid dose of 0.5mg/kg/day had similar efficacy as 1mg/kg/day dose.

Hepatitis A Virus Infection-Associated Hemophagocytic Lymphohistiocytosis in Two Children

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome characterized by high fever, maculopapular rash, neurological symptoms, abnormal liver functions and coagulopathy. Primary HLH is due to an underlying genetic abnormality. Secondary HLH are due to an underlying infection, autoimmune disease or malignancy. Secondary HLH due to viral infections are commonly due to the herpes group commonest of which is the Ebstein Barr virus (EBV). We describe two children with virus associated hemophagocytic lymphohistiocytosis (VAHLH) secondary to hepatitis A infection.

An Unusual Association of Chronic Recurrent Multifocal Osteomyelitis, Pyoderma Gangrenosum, and Takayasu Arteritis.

To the Editor: Chronic recurrent multifocal osteomyelitis (CRMO) is hypothesized to be an autoimmune disorder because of its association with multiple autoimmune diseases, including inflammatory bowel disease, psoriasis, acne, pustulosis, Sweet syndrome, dyserythropoietic anemia, pyoderma gangrenosum (PG), sclerosing cholangitis, inflammatory arthritis, Still disease, Takayasu arteritis (TA), Ollier disease, and dermatomyositis1,2. PG association with TA is rare; however, Ujiie, et al showed that PG is associated with TA in 33% of patients3. Occurrence of all 3 conditions together (CRMO, PG, and TA) is very rarely reported. A 10-year-old girl born to nonconsanguineous parents presented with a history of intermittent swelling over the right side of the mandible, associated with pain and claudication pain over legs and back with breathlessness on exertion for the past 2 years. She also developed ulcerative cauliflower-like skin lesions over the dorsum of left foot over the past 2 months (Figure 1). On examination, her pulses were absent … Address correspondence to Dr. S. Kumar, Christian Medical College, Department of Pediatrics, Christian Medical College, Vellore, Tamil Nadu 632004, India. E-mail: sathishkumar{at}cmcvellore.ac.in

A novel de-novo frameshift mutation of the ASXL1 gene in a classic case of Bohring-Opitz syndrome.

Introduction Since the initial description of the Bohring–Opitz syndrome as a rare but distinct entity from the C syndrome/ Opitz trigonocephaly syndrome by Dr Axel Bohring in 1999, only 52 cases worldwide have been described in the peer-reviewed literature (Dangiolo et al., 2015; Russell et al., 2015). The majority of these cases were considered to have Bohring–Opitz syndrome (BOPS) as they fulfilled the clinical diagnostic criteria established by Hastings et al. (2011); however, only a minority have a confirmed molecular diagnosis to date. Hoischen et al. (2011) used exome sequencing in three classical BOPS cases with a similar phenotype to find heterozygous denovo nonsense mutations in the ASXL1 (additional sex combs-like transcriptional regulator 1) gene to be responsible for BOPS when the traditional methods had failed to do so. They also found the disease-causing variants in another four cases with the BOPS phenotype in the ASXL1 gene (Hoischen et al., 2011). The majority of cases (50%) that fulfil the clinical criteria have been shown to carry de-novo mutations in the ASXL1 gene, a member of the polycomb group of genes, essential for the regulation of some of theHOX genes at a critical period of development.

Systemic Juvenile Idiopathic Arthritis: Diagnosis and Management

Systemic juvenile idiopathic arthritis (sJIA) is an inflammatory condition characterized by fever, lymphadenopathy, arthritis, rash and serositis. In sJIA, systemic inflammation has been associated with dysregulation of the innate immune system, suggesting that it is an autoinflammatory disorder. IL-1 and IL-6 play a major role in the pathogenesis of sJIA and treatment with IL-1 and IL-6 inhibitors has shown to be highly effective. Recent data suggests that early cytokine blockage might abrogate chronic, destructive, therapy resistant arthritis phase, reflecting a potential “window of opportunity” in the care of children with sJIA.