Minocycline-induced drug reaction with eosinophilia and systemic symptoms (DRESS) masquerading as acute leukemia.

ABSTRACT: Drug reaction with eosinophilia and systemic symptoms (DRESS) is an idiosyncratic drug reaction characterized by fever, rash, and lymphadenopathy associated with atypical lymphocytosis and eosinophilia. Visceral organ involvement is also seen and hence it often mimics hematolymphoid malignancies. A 19-year-old girl presented with generalized pruritic rash, fever, lymphadenopathy, and lymphocytosis. Subsequently, she developed respiratory distress with a fall in SpO2. Flow cytometry, bone marrow studies, and infectious workup were normal. Skin biopsy and clinical assessment criteria established the diagnosis of DRESS secondary to minocycline intake. Discontinuation of the offending drug is most important to abet the hypersensitivity reaction. Visceral organ involvement requires the use of steroids and immunosuppressive agents. Our patient responded well to treatment and is presently symptom-free and on follow-up for the last 6 months.

Rare complications of heart transplant: Autopsy findings.

BACKGROUND: Heart transplantation has evolved as the only treatment option for patients with refractory heart failure. CASE PRESENTATION: We here, report two unusual complications that developed following cardiac transplant to which the recipients succumbed. Post mortem conducted revealed the cause of death as severe antibody mediated rejection in one case and ruptured mycotic aneurysm of ascending aorta in the second recipient. CONCLUSION: Hence, autopsy remains the key procedure that can help establish the cause of death after cardiac transplant. It is also imperative for clinicians to have awareness and high index of suspicion for early detection of the ongoing complications and intervene either surgically or medically to prevent catastrophic events.

A Young Female With Takayasu Arteritis Involving the Coronary Arteries.

A rare form of large vessel vasculitis, Takayasu arteritis (TA) typically affects the aorta and its primary branches and rarely involves the coronary arteries. We present a case study of a female patient who had refractory hypertension and coronary artery disease for which she underwent percutaneous transluminal angioplasty. Subsequently, she was diagnosed with Takayasu arteritis. We wish to underscore the significance of timely identification and intervention as pivotal factors in improving patient outcomes and optimizing the effectiveness of therapeutic strategies in managing TA.

Acceptability and feasibility of assisted telepsychiatry in routine healthcare settings in India: a qualitative study.

Technology-enabled interventions are often recommended to overcome geographical barriers to access and inequitable distribution of mental healthcare workers. The aim of this study was to examine the acceptability and feasibility of an assisted telepsychiatry model implemented in primary care settings in India. In-depth interviews were conducted with patients who received telepsychiatry consultations. Data were collected about domains such as experience with communicating with psychiatrists over a video call and feasibility of accessing services. Data were analysed using a thematic analysis approach. Patients recognized that technology enabled them to access treatment and appreciated its contribution to the improvement in their mental health condition. They reported that the telepsychiatry experience was comparable to face-to-face consultations. They had a positive experience of facilitation by counsellors and found treatment delivery in primary care non-stigmatizing. While some adapted easily to the technology platform because of increased access to technology in their daily lives, others struggled to communicate over a screen. For some, availability of care closer to their homes was convenient; for others, even the little travel involved posed a financial burden. In some cases, the internet connectivity was poor and interfered with the video calls. Patients believed that scale could be achieved through adoption of this model by the public sector, collaboration with civil society, enhanced demand generation strategies and leveraging platforms beyond health systems. Assisted telepsychiatry integrated in routine healthcare settings has the potential to make scarce specialist mental health services accessible in low resource settings by overcoming geographical and logistical barriers.

Interleukin-9 rescues class switching of Memory B cells derived from Common variable immunodeficiency patients.

Impaired class switch memory (CSM) B cell formation is the hallmark of common variable immunodeficiency (CVID). Various T cell abnormalities have been observed in CVID patients indicating inadequate T-cell help to B cells. A major setback in understanding its pathogenesis is due to diverse clinical presentation. Therefore, we performed extensive immunological investigation in a cohort of CVID patients with similar clinical findings in order to unravel the T cell dysfunction and its influence on the defective humoral immune response. All recruited CVID patients exhibited B cells in the normal range, but reduced CSM B cells. However, patients showed reduced T cell proliferation, reduced level of serum Interleukin-9 (IL-9) and frequency of IL-9 expressing CD4 (Th-9) cells. IL-9 supplementation along with CD40 engagement was effective in inducing in vitro CSM B cells formation in CVID patients. Thus, IL-9 supplementation has the potential to restore impaired CSM B cell formation in CVID.

Adolescent Health Series: The status of adolescent mental health research, practice and policy in sub-Saharan Africa: A narrative review.

Sub-Saharan Africa (SSA) has the fastest growing adolescent population in the world. In addition to developmental changes, adolescents in SSA face health and socioeconomic challenges that increase their vulnerability to mental ill-health. This paper is a narrative review of adolescent mental health (AMH) in SSA with a focus on past achievements, current developments, and future directions in the areas of research, practice and policy in the region. We describe the status of AMH in the region, critical factors that negatively impact AMH, and the ways in which research, practice and policy have responded to this need. Depression, anxiety and post-traumatic stress disorders are the most common mental health problems among adolescents in SSA. Intervention development has largely been focused on HIV/AIDS service delivery in school or community programs by non-specialist health workers. There is a severe shortage of specialised AMH services, poor integration of services into primary health care, lack of a coordinated inter-sectoral collaboration, and the absence of clear referral pathways. Policies for the promotion of AMH have been given less attention by policymakers, due to stigma attached to mental health problems, and an insufficient understanding of the link between mental health and social determinants, such as poverty. Given these gaps, traditional healers are the most accessible care available to help-seeking adolescents. Sustained AMH research with a focus on the socioeconomic benefits of implementing evidence-based, contextually adapted psychosocial interventions might prove useful in advocating for much needed policies to improve AMH in SSA.

An Unusual Clinical Manifestation of Plasmablastic Lymphoma in a Renal Transplant Recipient.

Plasmablastic lymphoma is a rapidly progressive CD20 negative large cell non-Hodgkin lymphoma with poor outcome. It occurs mostly in immunocompromised individuals and has a predilection for extranodal sites. They need to be differentiated from other entities sharing similar morphological features like poorly differentiated carcinoma, Burkitt's lymphoma, Alk positive large B cell lymphoma, Diffuse large B cell lymphoma, and anaplastic myeloma. EBV negativity in recipients, type, intensity, and duration of immunosuppressives used are certain risk factors in development of posttransplant lymphoproliferative disorders. High index of suspicion can help clinch the diagnosis early and prevent catastrophic consequences. Our renal transplant recipient presented with complaints of pain abdomen and malena for which he underwent exploratory laparotomy. Diagnosis was established on histopathology and timely treatment initiated reverted the disease.

Integrating assisted tele-psychiatry into primary healthcare in Goa, India: a feasibility study.

Background: Tele-psychiatry is an increasingly acceptable and feasible platform to deliver mental health care with the potential to increase access to care in low-resource settings. We aim to examine the acceptability and preliminary impact of the delivery of assisted tele-psychiatry services in primary healthcare settings in Goa, India. Methods: Before-after uncontrolled treatment cohort study. In total, 161 adults with either a mental or alcohol use disorder were provided tele-consultation by psychiatrists through a customised video conferencing platform, along with medication or counselling (via trained lay counsellors) or both as needed. Data on socio-demographics, clinical outcomes and process indicators were collected at baseline and 3 months post-baseline. Paired t tests were used to assess clinical outcomes pre- and post-treatment using the General Health Questionnaire-12 (GHQ-12) and World Health Organisation Disability Adjustment Schedule (WHODAS) 2.0, and logistic regression was used to find associations between changes in these scores and various factors. Results: The most common diagnosis was depression (35%). Post-treatment, there was a significant reduction in both GHQ-12 and WHODAS 2.0 scores. Participants showed high satisfaction with the tele-psychiatry services and technology platform. Improvement in GHQ-12 score was associated with being employed [OR 8.74 (1.92-39.75, p = 0.005)] and being a homemaker [OR 6.42 (CI 1.61-25.57, p = 0.008)]. Conclusion: Treatment of mental disorders through a tele-psychiatry platform appears to be highly acceptable and is associated with improved clinical outcomes. Considering its potential for scalability, a model of assisted tele-psychiatry integrated into primary care can be an important strategy to increase access to mental healthcare in low-resource settings.

Alcohol use among adolescents in India: a systematic review.

Background: Alcohol use is typically established during adolescence and initiation of use at a young age poses risks for short- and long-term health and social outcomes. However, there is limited understanding of the onset, progression and impact of alcohol use among adolescents in India. The aim of this review is to synthesise the evidence about prevalence, patterns and correlates of alcohol use and alcohol use disorders in adolescents from India. Methods: Systematic review was conducted using relevant online databases, grey literature and unpublished data/outcomes from subject experts. Inclusion and exclusion criteria were developed and applied to screening rounds. Titles and abstracts were screened by two independent reviewers for eligibility, and then full texts were assessed for inclusion. Narrative synthesis of the eligible studies was conducted. Results: Fifty-five peer-reviewed papers and one report were eligible for inclusion in this review. Prevalence of ever or lifetime alcohol consumption ranged from 3.9% to 69.8%; and prevalence of alcohol consumption at least once in the past year ranged from 10.6% to 32.9%. The mean age for initiation of drinking ranged from 14.4 to 18.3 years. Some correlates associated with alcohol consumption included being male, older age, academic difficulties, parental use of alcohol or tobacco, non-contact sexual abuse and perpetuation of violence. Conclusion: The evidence base for alcohol use among adolescents in India needs a deeper exploration. Despite gaps in the evidence base, this synthesis provides a reasonable understanding of alcohol use among adolescents in India and can provide direction to policymakers.

The systematic development of a mobile phone-delivered brief intervention for hazardous drinking in India.

BACKGROUND: The treatment gap for alcohol use disorders (AUD) in India is the highest among all mental health and substance use disorders. Despite evidence of the cost effectiveness of brief interventions (BIs) for hazardous drinking, implementation in low- and middle-income countries (LMICs) is rare due to several human resource-related barriers. This paper describes the processes and outputs of a study aimed at systematically developing a mobile phone-delivered BI to overcome such barriers. METHODS: This is a mixed methods study with four steps: (1) Review of existing relevant evidence base by extracting data from studies cited in two recent, relevant and high-quality systematic reviews; (2) In-depth interviews (IDIs) with 11 national experts in addictions research and practice, and 22 hazardous drinkers; (3) Delphi survey (2 rounds) to identify components for the intervention package through consensus building; and (4) Content and intervention development workshops with a range of stakeholders to develop the intervention package. RESULTS: The research team sourced 72 journal articles from two selected systematic reviews. Key content areas extracted from the studies included facts and statistics about health related to drinking behavior, self-reflection, goal-setting messages, motivational messages, and skills to manage risky situations. The IDIs with experts and hazardous drinkers endorsed most of these content areas as well. The Delphi survey achieved consensus on 19 content areas, which included targeted recommendations, personalized feedback and information, goal management, and coping skills. The content and intervention development workshops resulted in an intervention package delivered over 8 weeks, with the following seven themes guiding the content of the weekly messages: safe drinking/health education, alcohol reduction, drinking and risk management, drinking alternatives, situational content, urge management, and maintenance and relapse prevention. CONCLUSION: The research team designed this study to consider contextual factors while developing the intervention, which is important to ensure acceptability and feasibility of the intervention. Interestingly, the contextually informed intervention components had several commonalities with BIs developed and tested in high-income countries.

Is Twice-weekly Maintenance Hemodialysis Justified?

BACKGROUND: The benefits of twice-weekly dialysis at initiation are significant with respect to access longevity, preservation of residual renal function, economic factors, and patient quality of life. It is widely practiced in developing countries due to resource and financial constraints. We present a 3-year follow-up of patients on twice-weekly dialysis and their outcomes. MATERIAL AND METHODS: This was a 3-year observational follow-up study of patients initiated on twice-weekly hemodialysis. Adequacy and basic cost-effective hematological and biochemical parameters were studied monthly. In case of complications, the patient was shifted to thrice-weekly hemodialysis. RESULTS: 88 incident hemodialysis patients were followed up. Total sessions of hemodialysis (HD) studied were 16,406. The mean hemoglobin level was 9.53 g/dl with hyperphosphatemia in 74.88% patients. The mean residual renal function (RRF) at initiation was 5.71 +/- 3.70 ml/min. The mean interdialytic weight gain was 1.91 +/- 1.26 kg with a mean ultrafiltration of 2600 ± 410 ml. The spKt/V and eKt/V were adequate in 68.54% and 48.34% patients; however, the standard Kt/V of 2 was achieved in only 10.51% patients. Emergency HD was done in 41 sessions (0.24%). There were 24 deaths (27.27%) during this period with the mean time to mortality being 503.12 +/- 296.62 days. CONCLUSION: Initiation at twice-weekly schedules for patients on maintenance hemodialysis is a viable option with increments in case of requirement, more so in patients with good urine output and residual renal function. The biochemical and hematological parameters were stable and within KDOQI guidelines and do not worsen with time.

Posttransplant lymphoproliferative disorder in renal transplant recipients: Experience from a Tertiary Care Center.

Posttransplant lymphoproliferative disorders (PTLDs) are potentially fatal complications arising after solid organ or hematopoietic stem cell transplant. The most crucial factor in pathogenesis of PTLDs is either a primary infection with Epstein-Barr virus or reactivation of its latent state due to immune dysregulation. This complex pathobiology leads to a myriad of clinical manifestations due to uncontrolled lymphoproliferation that may be reactive, polymorphous or monomorphous. We report our experience at a tertiary center of six cases detected over a span of six years. All our patients were proven as high grade B-cell lymphoma on histopathology, which remains the gold standard for diagnosis. Two cases were of primary central nervous system lymphoma, two had disseminated disease, fifth showed allograft involvement, and last case presented with gastrointestinal obstruction. All the patients were managed with reduction of immunosuppression, chemotherapeutic agents, and rituximab. Five patients responded well with a follow-up period of 3-28 months since the time of treatment initiation and had preserved renal function with no episodes of disease recurrence or allograft rejection.

Primary Ewing sarcoma/primitive neuroectodermal tumor of the lung.

We present the autopsy findings and differential diagnosis in a 42year old male who presented with fever and rapidly progressive respiratory symptoms like breathlessness, nonproductive cough and right sided chest pain. Initial imaging workup done at our hospital revealed a large unilateral tumor with tracheal shift. While being evaluated patient developed facial puffiness, tachypnea suggestive of superior vena cava obstruction. Antemortem biopsy of lung mass was attempted twice and that suggested malignant lesion. Unfortunately, the individual had a rapid downhill course following admission. Post mortem examination was conducted that on opening the thoracic cavity revealed total replacement of right lung tissue by a necrotic growth which was deeply adherent to the rib cage. The contralateral lung as well as all other visceral organs were unremarkable grossly. Histopathology confirmed primary Ewing sarcoma of the lung. We hereby, report a rare case of primary lung Ewing sarcoma diagnosed at autopsy.

Post Transplant Lymphoproliferative Disorder.

Posttransplant lymphoproliferative disorder is an extremely fatal complication arising in transplant recipients as a side effect of immunosuppression. PTLDs are seen after both solid organ and hematopoietic stem cell transplants though the incidence is much higher in the former. Primary Epstein-Barr virus (EBV) infection or reactivation due to a state of immune dysregulation along with intensity of immunosuppression used are of paramount importance in pathogenesis of PTLD. EBV associated PTLDs occur early in the post transplant period whereas late onset lymphomas are usually EBV negative. The uncontrolled B cell proliferation can create a spectrum of histological patterns from nondestructive lesions to destructive polymorphic or more aggressive monomorphic PTLDs. Early detection of seropositivity by serial monitoring in the recipient can prevent PTLD development by starting pre-emptive therapy. The mainstay treatment in established cases remains reduction of immunosuppression. Chemotherapeutic and immunomodulatory agents are added sequentially based on the type of PTLD and based on its response to initial therapy. Despite various treatment options available, the morbidity remains high and achieving state of disease remission without causing graft rejection can be quite challenging. Hence, a better understanding in pathobiology of EBV+ versus EBV- PTLDS may help prevent lymphomagenesis in transplant recipients.

Successful reconstitution of leukocyte adhesion defect after umbilical cord blood stem cell transplant.

Leukocyte adhesion deficiencies (LADs) are a type of primary immunodeficiencies characterized by delayed detachment of the umbilical cord, impaired wound healing, leukocytosis, and recurrent infections. The disease is caused by genetic defects affecting different steps in the process of leukocyte adhesion cascade such as rolling, integrin activation, and adhesion of leukocytes, resulting in the impairment of leukocyte trafficking. Till date, three types of LAD have been documented: type I, II and III. Type I LAD is caused by congenital defect in the ß2 integrin receptor complex CD11/CD18 on the cell surface of leukocytes, which results in impaired leukocytes connection to endothelial cells and migration. Type II LAD is caused by defect in the fucose metabolism resulting in the absence of fucosylated selectin ligands on neutrophils and impaired rolling phase of the leukocyte adhesion cascade. Type III LAD is caused by mutations in the kindlin-3 gene resulting in defective integrin activation. In this article, we present a review of literature for type I LAD, and successful treatment of patient using umbilical cord blood stem cell transplantation.

Primary Ewing sarcoma/primitive neuroectodermal tumor of the lung

We present the autopsy findings and differential diagnosis in a 42year old male who presented with fever and rapidly progressive respiratory symptoms like breathlessness, nonproductive cough and right sided chest pain. Initial imaging workup done at our hospital revealed a large unilateral tumor with tracheal shift. While being evaluated patient developed facial puffiness, tachypnea suggestive of superior vena cava obstruction. Antemortem biopsy of lung mass was attempted twice and that suggested malignant lesion. Unfortunately, the individual had a rapid downhill course following admission. Post mortem examination was conducted that on opening the thoracic cavity revealed total replacement of right lung tissue by a necrotic growth which was deeply adherent to the rib cage. The contralateral lung as well as all other visceral organs were unremarkable grossly. Histopathology confirmed primary Ewing sarcoma of the lung. We hereby, report a rare case of primary lung Ewing sarcoma diagnosed at autopsy.

Primary Immunodeficiency Disorders Among North Indian Children.

OBJECTIVES: To report the distribution pattern of various categories of primary immunodeficiency disorders (PIDs) in children from North India, frequency of warning signs and critical parameters for evaluation. METHODS: In this retrospective study, 528 children below 18 y of age after clinical assessment and presentation suggestive of PID were further screened by immunophenotyping for immune cell markers by flow cytometry. RESULTS: A total of 120 (23%) children were diagnosed with PID with median age at diagnosis being 2.5 y in males and 3.5 y in females and an average delay in diagnosis from onset of symptoms being approximately 5 y. Chronic lower respiratory tract infections, gastrointestinal symptoms like persistent diarrhea and failure to thrive were amongst the most common warning signs in these patients. PIDs were classified according to the International Union of Immunological Societies' (IUIS) criteria. The diagnosis of index study subjects included combined humoral and cellular immunodeficiency (29%), phagocytic defects (29%), followed by predominantly antibody deficiency (18%), innate immunity and dysregulation (17%) and other well-defined syndromes (7%). A family history of PID (23%), consanguineous marriage (8%) and previous sibling death (23%) were observed as major clinical predictors/clues for underlying PID. All children received prophylactic antibiotics and/or antifungals in addition to specific therapy for underlying immune deficiency. CONCLUSIONS: The field of PIDs in India remains largely unexplored and we are faced with various challenges in the diagnosis of PIDs due to lack of awareness as well as absence of equipped immunological laboratory support. The authors propose a methodical step-wise laboratory diagnostic approach that can facilitate early diagnosis and timely intervention of these mis/underdiagnosed disorders.

Hematopoietic stem cell transplantation in children with Griscelli Syndrome type 2: Experience and outcomes.

Griscelli syndrome is a rare autosomal recessive inherited disorder characterized by hypopigmentation, silver colored hair, and associated immunological deficiency, which proves fatal in the absence of timely intervention. Our patients diagnosed with Griscelli syndrome-2 presented with fever, hepatosplenomegaly, and deranged hematological and biochemical parameters. Both cases underwent detailed investigations comprising of hair mount microscopic examination, degranulation assay, and mutational studies. Our cases showed defective degranulation activity by NK cells and gene mutation analysis revealed RAB27A mutation that causes defect of cytotoxic granule exocytosis from natural killer (NK) and T-cells, manifesting clinically as hemophagocytic lymphohistiocytosis (HLH). Hematopoietic stem cell transplantation in one of the patients resulted in stable chimerism; however, the second case relapsed within a month after SCT. Stem cell transplantation is the only curative therapeutic option for GS2; thus, improvement in posttransplantation management may reduce mortality and posttransplant complications. Hence, any child who presents with partial albinism and clinical features suggestive of HLH, a peripheral blood, hair shaft mount examination along with basic immunological NK and T-cell cytotoxicity assay by flow cytometry will help clinch the diagnosis early. It can subsequently be confirmed by molecular study. Timely therapeutic intervention can prevent relapses and severe infection and improve outcome in these cases.

Diminished CD40L expression on T-cells in a case of disseminated cryptococcosis.

X-linked hyperimmunoglobulin M (HIGM) syndrome may increase the susceptibility of patients to disseminated cryptococcal infections primarily due to CD40L deficiency that causes defective cross talk between T- and B-cells, thus preventing class switching. In HIGM syndrome, serum IgM levels are elevated with severe reduction in serum immunoglobulin G (IgG) and IgA levels. In addition, the expression of CD40L (CD154) on in vitro-activated T-cells is severely reduced or absent. Here, we describe a rare, and perhaps, the first reported case in India of a 3-year-old male child with X-linked HIGM immunodeficiency syndrome who developed disseminated Cryptococcosis. Evaluation of the serum IgG profile of the patient revealed increased serum IgM levels with reduced IgG and IgA levels. Both the frequency and the function of T-cells, primarily CD40L on activated T-cells, showed weak expression suggestive of HIGM syndrome.