Alopecia in Multiple Sclerosis Patients Treated with Disease Modifying Therapies.

BACKGROUND: There is currently limited literature addressing the reporting of alopecia in multiple sclerosis (MS) patients treated with disease-modifying therapies (DMTs). Anecdotal reports of hair thinning from patients on various DMTs prompted further investigation of a large database. OBJECTIVE: To analyze total reports, source of reporting, age distribution, and sex distribution of alopecia associated with DMTs. METHODS: FDA Adverse Event Reporting System (FAERS) public dashboard and OpenFDA database were analyzed for alopecia reports between January 1, 2009, and June 30, 2020, attributed to usage in MS of FDA approved DMTs. The main outcomes included total reports for each drug, age, sex distribution, and reporting source. OpenFDA data was used for statistical analyses including reporting odds ratios (ROR) and information components. RESULTS: 8759 alopecia reports were identified among 44 114 adverse events in skin and subcutaneous tissue disorders (19.9%). 3701 (42.3%) with teriflunomide, 1675 (19.1%) with dimethyl fumarate, 985 (11.2%) with natalizumab, 926 (10.6%) with fingolimod, 659 (7.5%) with interferon beta-1a, 257 (2.9%) with glatiramer acetate, 243 (2.8%) with ocrelizumab, 124 (1.4%) with interferon beta-1b, 117 (1.3%) with alemtuzumab, 36 (.4%) with siponimod, 24 (.3%) with cladribine, and 12 (.1%) with rituximab. Reports were mostly made by patients (78.3%) and highest in fifth and sixth decades of life. OpenFDA analyses showed increased ROR (ROR 95% confidence interval) of alopecia in females with teriflunomide (18.00, 17.12-18.93), alemtuzumab (1.43, 1.16-1.76), dimethyl fumarate (1.26, 1.18-1.34), and ocrelizumab (1.28, 1.11-1.49). Increased ROR in males was associated with teriflunomide (24.65, 20.72-29.31). CONCLUSION: We identified many reports of alopecia for DMTs in addition to teriflunomide. Within the limitations of the database, increased RORs of alopecia were observed for females treated with alemtuzumab, dimethyl fumarate, and ocrelizumab. The source of reporting was largely driven by female patients. Possible alopecia, even if transient, should be considered during patient education when starting DMTs.

Disproportional increase in psoriasis reports in association with B cell depleting therapies in patients with multiple sclerosis.

BACKGROUND: Some pathways involved in the pathogenesis of psoriasis share similarities with processes involved in multiple sclerosis (MS) pathogenesis. However, the association between MS and psoriasis is poorly understood. Since disease-modifying therapies for MS have various targets, it may be possible that the occurrence of psoriasis varies by drug. OBJECTIVE: To analyze the frequency of psoriasis reports in patients treated with various disease-modifying therapies for MS. METHODS: Data was collected using the FDA Adverse Event Reporting System (FAERS) and OpenFDA database between January 2009 and June 2020. The study analyzed total reports of psoriasis out of total reports in the "Skin and Subcutaneous Tissue Disorders" category for each drug and explored age, sex distribution, and report source. OpenFDA data was used to perform statistical analyses including reporting odds ratios (ROR) and information components. RESULTS: The study identified 517 psoriasis reports of 45,547 total skin and subcutaneous tissue disorders (1.13%) in FAERS. The highest proportions of reports in this study were associated with rituximab, ocrelizumab, and interferon beta 1a. The lowest proportion of reports were associated with glatiramer acetate, alemtuzumab, dimethyl fumarate and teriflunomide. Reports of other autoimmune skin disorders were minimal (29 vitiligo, 33 pemphigoid, and 7 pemphigus). Patients primarily drove reports for most DMTs versus healthcare providers. The proportion of reports from female patients were the highest for each DMT except alemtuzumab. OpenFDA query retrieved 302 total reports of psoriasis. Significantly increased reporting odds ratios (RORs, 95% confidence interval) of psoriasis were noted for rituximab (7.14, 3.92-13.00), ocrelizumab (3.79, 2.74-5.23), and fingolimod (1.33, 1.01-1.76). Significantly decreased RORs were noted for natalizumab (0.53, 0.36-0.80), glatiramer acetate (0.58, 0.35-0.96), and dimethyl fumarate (0.71, 0.53-0.94). CONCLUSION: There are frequent reports of psoriasis in MS patients treated with various DMTs. However, reports and RORs were disproportionally high in association with B cell depleting therapies. Further research is required to determine if certain DMTs may serve as better options for individuals affected by, or at high-risk for developing psoriasis.

The Effect of Neutropenia and Filgrastim (G-CSF) on Cancer Patients With Coronavirus Disease 2019 (COVID-19) Infection.

BACKGROUND: Neutropenia is commonly encountered in cancer patients. Recombinant human granulocyte colony-stimulating factor (G-CSF, filgrastim), a cytokine that initiates proliferation and differentiation of mature granulocytes, is widely given to oncology patients to counteract neutropenia, reducing susceptibility to infection. However, the clinical impact of neutropenia and G-CSF use in cancer patients with coronavirus disease 2019 (COVID-19) remains unknown. METHODS: An observational cohort of 379 actively treated cancer patients with COVID-19 was assembled to investigate links between concurrent neutropenia and G-CSF administration on COVID-19-associated respiratory failure and death. These factors were encoded as time-dependent predictors in an extended Cox model, controlling for age and underlying cancer diagnosis. To determine whether the degree of granulocyte response to G-CSF affected outcomes, the degree of response to G-CSF, based on rise in absolute neutrophil count (ANC) 24 hours after growth factor administration, was also incorporated into a similar Cox model. RESULTS: In the setting of active COVID-19 infection, outpatient receipt of G-CSF led to an increased number of hospitalizations (hazard ratio [HR]: 3.54, 95% confidence interval [CI]: 1.25-10.0, P value: .017). Furthermore, among inpatients, G-CSF administration was associated with increased need for high levels of oxygen supplementation and death (HR: 3.56, 95% CI: 1.19-10.2, P value: .024). This effect was predominantly seen in patients that exhibited a high response to G-CSF based on their ANC increase post-G-CSF administration (HR: 7.78, 95% CI: 2.05-27.9, P value: .004). CONCLUSIONS: The potential risks versus benefits of G-CSF administration should be considered in neutropenic cancer patients with COVID-19, because G-CSF administration may lead to worsening clinical and respiratory status.

Negative Impact of Vestibular Suppressant Drugs on Provocative Positional Tests of BPPV: A Study from the Western Part of India.

AIMS: To study the impact of vestibular suppressant drugs (VSD) on provocative positional tests (PPT) in patients with benign paroxysmal positional vertigo (BPPV). SETTINGS AND DESIGN: A prospective case-control observational study. MATERIALS AND METHODS: Patients with a history suggestive of BPPV were tested for PPT. Patients with vertiginous symptoms and with nystagmus on PPT were classified as objective BPPV (O-BPPV, control group), while those without nystagmus with no alternate diagnosis were classified as subjective BPPV (S-BPPV, case group). Details of VSD treatment were noted in all the patients. In both groups, patients were instructed to discontinue VSD and were further assigned as the VSD and non-VSD subgroups. Patients were followed for 2 months with PPT every week. PPT positive patients were treated by vestibular rehabilitation maneuvers. STATISTICS: Student t-test with two-tailed, unpaired, was used for continuous scale and Chi-square test for categorical differences between the two groups. RESULTS: 295 consecutive BPPV patients were enrolled in the study, 55 in the S-BPPV group and 240 in the O-BPPV group. Significantly higher proportion of patients in the S-BPPV group were on VSD at presentation, 80.00% vs. 53.75% (OR 2.52; 95% CI: 1.30-4.86), P = 0.006. In an unadjusted analysis of the S-BPPV group following discontinuation of VSD, PPT became positive in 79.54% of patients as compared to 18.19% in the non-VSD group (OR 35.0; 95% CI: 6.2-197.3), P < 0.001. CONCLUSION: A higher proportion of S-BPPV patients were receiving VSD in comparison to O-BPPV at the initial visit. The PPT converted positive four times higher after ceasing the VSD in S-BPPV patients. STUDY DESIGN: Prospective case-control observational study.

Penicillin Allergy Testing: An Outpatient Nurse-Driven Program for Patients With Cancer.

BACKGROUND: Penicillin allergy testing (PAT) can decrease the use of unnecessary antibiotics by clarifying who is truly allergic. OBJECTIVES: This article describes the development and implementation of an oncology outpatient nurse-driven PAT program. METHODS: A nurse-driven program, initiated with allergy screening at the first encounter, was designed to identify patients with oncologic diagnoses eligible for PAT. Once verified eligible, patients undergo a three-step testing process (scratch test, intradermal injection, and IV challenge dose) administered by the infusion nurse. FINDINGS: From November 2018 to December 2019, 82 outpatients with reported penicillin allergies were screened; 90% were eligible for PAT, and 97% of patients tested were negative for penicillin allergy. A significant reduction in aztreonam use among patients admitted for hematopoietic stem cell transplantation was also noted as compared to before PAT was offered.

Adrenocortical Crisis Triggered by Levothyroxine in an Unrecognized Autoimmune Polyglandular Syndrome Type-2: A Case Report with Review of the Literature.

BACKGROUND: Autoimmune polyglandular syndrometype-2 (APS-2) is an uncommon endocrine disorder of Addison's disease with an autoimmune thyroid disorder and/or type 1 diabetes mellitus. The diagnosis is more challenging when a patient presents with nonspecific neuropsychiatric features with hypothyroidism in the setting of unrecognized Addison's disease. CASE REPORT: We report a case of subclinical autoimmune hypothyroidism presented with nonspecific neuropsychiatric symptoms precipitated by stress. Despite levothyroxine treatment, her symptoms deteriorated and she was admitted with persistent vomiting and hypovolemic shock. Clinical features and laboratory parameters were suggestive of underlying adrenocortical insufficiency. Preexisting autoimmune hypothyroidism combined with Addison's disease confirmed the diagnosis of unrecognized APS-2. She remarkably improved and her thyroid function tests also normalized with the treatment of corticosteroids only. REVIEW OF THE LITERATURE: We identified only five published case reports of our title by searching the database. Neufeld and Betterle have reported their data of APS-2 and concluded that a full- blown clinical picture of two or more components of the syndrome is like the tip of the iceberg. CONCLUSION: The patients of one major component of APS-2 should be screened for other components of the disease to pick up latent cases. Addison's disease should be ruled out in patients of hypothyroidism who are intolerant to levothyroxine.

Diagnostic Value of Dynamic High-frequency Ultrasound for the Slipping Rib and Twelfth Rib Syndrome: A Case Series with Review.

BACKGROUND: High-frequency ultrasound (HFUS) is a mobile, radiation-free imaging tool for the diagnosis of musculoskeletal disorders. We aim to demonstrate the diagnostic value of dynamic HFUS for undiagnosed lower chest, upper abdomen, and loin pain with this case series. CASE SERIES: A cricketer presented with long-standing left-sided dull ache lower chest and upper abdominal pain, aggravated on exertion and leaning forward. His previous laboratory and previous imaging tests were unrevealing. Dynamic HFUS of his left ribs during hooking maneuver demonstrated slipping of the eighth rib over the seventh rib associated with clicking. He also reported tenderness over this region. He was diagnosed with slipping rib syndrome (SRS), and was treated with the eighth nerve block under the HFUS guidance. The second and third cases presented with chronic undiagnosed waxing and waning loin pain despite extensive laboratory and radiological workup. Both patients demonstrated twelfth rib HFUS probe tenderness in a sitting position with a specific movement that reproduced the pain during the dynamic HFUS study. The diagnosis of twelfth rib syndrome (TRS) was confirmed and treated successfully with a local intercostal nerve block. REVIEW OF THE LITERATURE: HFUS is the most underutilized imaging tool for the diagnosis of unexplained upper abdominal and lower chest pain syndromes. We identified only a few such reported cases managed with the help of HFUS. CONCLUSION: The dynamic HFUS is a valuable imaging modality for the undiagnosed lower chest, upper abdominal, or loin pain.

Association between socioeconomic status and influenza-like illness: A study from Western part of India.

OBJECTIVES: Health status is associated with socioeconomic status (SES) of the individuals. The aim of this study was to identify any link between the SES and influenza-like illness (ILI). MATERIALS AND METHODS: This observational case-control study was done on 18-70 years old patients presented with ILI (cases) at tertiary care hospital of western India. Controls were selected from demographically matched elective surgery patients except the SES. SES was evaluated as per the Modified B G Prasad 2017 scale and participants were further classified in lower SES (per capita income <2000 INR) and non-lower SES groups. RESULTS: 810 cases and 830 controls were compared. Many cases were from lower SES, had poor hand hygiene, and were using soil, mud, ash (SMA) for hand cleaning as compared to the control. Among the cases significant numbers were from lower SES (543/810[67%], P < 0.02), many were alcoholics, smokers, had poor hand hygiene, were using SMA for hand cleaning, and had preexisting chronic obstructive pulmonary disease (COPD), while few were having diabetes in the lower SES group as compared to the non-lower SES group. ILI was more common among lower SES class in unadjusted analysis (odds ratio [OR] 1.58, 95% CI 0.89-2.76) and the results were significant even after the adjustment of covariates (OR 1.62, 95% CI, 0.94-2.85). CONCLUSION: Lower SES people were 2.8 times more prone to ILI as compared to the age- and sex-matched control in western part of India.

The Effect of Neutropenia and Filgrastim (G-CSF) in Cancer Patients With COVID-19 Infection.

BACKGROUND: Neutropenia is commonly encountered in cancer patients, and recombinant human granulocyte colony-stimulating factor (G-CSF, filgrastim) is widely given to oncology patients to counteract neutropenia and prevent infection. G-CSF is both a growth factor and cytokine that initiates proliferation and differentiation of mature granulocytes. However, the clinical impact of neutropenia and G-CSF use in cancer patients, who are also afflicted with coronavirus disease 2019 (COVID-19), remains unknown. METHODS: An observational cohort of 304 hospitalized patients with COVID-19 at Memorial Sloan Kettering Cancer Center was assembled to investigate links between concurrent neutropenia (N=55) and G-CSF administration (N=16) on COVID-19-associated respiratory failure and death. These factors were assessed as time-dependent predictors using an extended Cox model, controlling for age and underlying cancer diagnosis. To determine whether the degree of granulocyte response to G-CSF affected outcomes, a similar model was constructed with patients that received G-CSF, categorized into high- and low-response, based on the level of absolute neutrophil count (ANC) rise 24 hours after growth factor administration. RESULTS: Neutropenia (ANC < 1 K/mcL) during COVID-19 course was not independently associated with severe respiratory failure or death (HR: 0.71, 95% Cl: 0.34-1.50, P value: 0.367) in hospitalized COVID-19 patients. When controlling for neutropenia, G-CSF administration was associated with increased need for high oxygen supplementation and death (HR: 2.97, 95% CI: 1.06-8.28, P value: 0.038). This effect was predominantly seen in patients that exhibited a high response to G-CSF based on their ANC increase post-G-CSF administration (HR: 5.18, 95% CI: 1.61-16.64, P value: 0.006). CONCLUSION: Possible risks versus benefits of G-CSF administration should be weighed in neutropenic cancer patients with COVID-19 infection, as G-CSF may lead to worsening clinical and respiratory status in this setting.

Medicated adhesive dressing is a safe and non-inferior cutaneous seal as compared to compound tincture benzoin dermal seal for percutaneous interventions.

BACKGROUND: Compound tincture benzoin (CTB) is used as a post-procedure skin seal antiseptic agent since ancient times; but this drug is reported to cause allergic contact dermatitis and other unwanted side effects. Our aim of the present study was to compare alternative agent like Medicated Adhesive dressing (MAD) with CTB as a post-procedure skin seal dressing. DESIGN: This prospective randomized controlled experimental study included an equal number of patients in MAD and CTB as a post-operative seal dressing material for percutaneous interventions. Both the groups were graded for various efficacy parameters like comfort, applicability, dressing material, and immediate post-operative complications by operating doctor and attending nurse with a maximum 10 points in each group. RESULTS: 120 patients were studied in each MAD and CTB group. Out of total patients 31.25% were males and the mean age of the patient was 33.56 ± 11.10. Allergic contact dermatitis developed in 9 (7.49%) of CTB group and in 1 (0.83%) of MAD group (P < 0.002), while local site skin infections were noted in 8 (6.67%) of CTB group and in 1 (0.83%) of MAD (P < 0.002). Operating doctor graded MAD and CTB to 7.60 ± 0.49 and 3.62 ± 0.48 (P < 0.003); and attending nurse 7.40 ± 0.49 and 3.41 ± 0.49 (P < 0.003) respectively. CONCLUSION: MAD is a safe, efficient and non-inferior alternative dressing material for post-procedure skin incision seal in comparison to CTB.

Non-uremic Calciphylaxis: A Rare and Late Adverse Reaction of Warfarin.

BACKGROUND: Calciphylaxis is a complex dermatological lesion of micro vascular calcification that is typically presented as panniculitis with gangrenous painful lesions having uremic and non-uremic causes. CASE REPORT: We present a case of a 48-year old male with a history of paroxysmal atrial fibrillation and hypertension taking amlodipine 5 mg and warfarin 5 mg daily for the last 26 months. The patient had a 6- months history of painful swelling followed by necrotic skin ulcer over the right leg. His remarkable examination findings were right leg tender ulcer with surrounding erythema and secondary sepsis. His hemogram, metabolic profile and connective tissue diseases work up were unremarkable except leucocytosis and raised inflammatory markers. His local part radiological and skin biopsy findings were suggestive of calciphylaxis. RESULTS AND CONCLUSION: In our case, warfarin and amlodipine were culprit drugs for the lesion, but Naranjo score (warfarin 7and amlodipine 1) speculate warfarin as a probable adverse reaction of warfarin. The lesion was cured with local wound treatment after discontinuation of warfarin. The physician should be aware of this rare cutaneous disorder of systemic origin for proper management.

Post Chikungunya Chronic Arthritis: Systemic Inflammatory Status Triggering Acute Coronary Syndrome.

BACKGROUND: Atherosclerosis, inflammation and coronary plaque destabilization are linked to each other. Infections due to various microbes may trigger Acute Coronary Syndrome (ACS) by systemic inflammation cascade. METHODS: We have evaluated the prevalence of Post Chikungunya Chronic Arthritis (PCCA) among 400 consecutive ACS patients (Case group) and compared with control group subjected to elective surgery by the prospective case-control observational study. Cases were excluded if standard criteria of ACS were not satisfied and in the control group if the patient suffered a Myocardial Infarction (MI) within 28 days of elective surgery. PCCA duration more than two years or serum IgM anti-CCP positive patients were also excluded from the case as well as a control group. RESULTS: The case and control groups were similar except, less number of heart failure (O.R.7.3, 95% C.I. 3.3-15.9) and chronic kidney injury patients (O.R. 0.5, 95% C.I. 0.3-0.9) in the elective surgery (control) group. PCCA was present in 24 out of 400 ACS cases and 8 out of 400 control group. Among ACS case-patients, those suffering from PCCA tended to be younger and more often women, with more diabetes, hypertension, chronic kidney injury and high mean CRP. In unadjusted analysis PCCA was three times more common in the case versus control (O.R. 3.0, 95% C.I. 1.4- 6.4); results were indistinguishable after multidiscipline adjustment (O.R. 3.0, 95% C.I. 1.3-6.8). CONCLUSION: PCCA is common among patients with ACS and post-infective systemic inflammation of PCCA may trigger plaque destabilization.

Phenytoin Induced Chorea: A Rare Adverse Effect of the Drug.

BACKGROUND: Dyskinetic neurological diseases are common presentations of adverse reaction to many therapeutic agents. Phenytoin, a widely used age-old antiepileptic drug has been reported to cause dyskinesias, a rare Adverse Drug Reaction (ADR) in adults with toxic therapeutic serum level. When the drug is used in combination with other drugs which augments free drug level of phenytoin or in patients of organic brain lesion, this side effect is very occasionally reported with even normal therapeutic drug level. CLINICAL CASE: We report a case of young male presented with chorea after two months of starting phenytoin for primary generalised epilepsy with normal therapeutic serum drug level. After excluding other differentials, drug-induced chorea was the final diagnosis. Despite phenytoin level was in therapeutic range, we have a trial of stopping Phenytoin with complete disappearance of chorea in 3 days. On reintroduction of phenytoin in the same dose, there was the reappearance of chorea in onemonth re-emphasising the diagnosis as "phenytoin-induced chorea". CONCLUSION: If any patient on phenytoin develops any new neurological feature including dyskinesias, it should be considered as an ADR despite drug serum level within the normal therapeutic range.

Pinpoint Localized Odynophagia (PLO) as a Specific Symptom of Pill-induced Oesophagitis (PIO) in the Evaluation of Acute Retrosternal Chest Pain.

INTRODUCTION: 36 out of 100 cases of retrosternal chest pains are due to oesophageal pathologies, and Pill-induced Oesophagitis (PIO) is one of them. PIO can present as retrosternal chest pain associated with various Gastrointestinal (GI) symptoms and require a high index of suspicion. PIO is a clinical diagnosis; and oesophagogastroscopy is required for confirmation of the diagnosis, to find out complications of PIO and to rule out other oesophageal disorders. Our aims of the present study were to study clinical profile, risk factors and endoscopic features of PIO. MATERIALS AND METHODS: We have done a cross-sectional study of 1000 patients with acute retrosternal chest pain, and all patients of suspected upper gastrointestinal system involvement were subjected to oesophagogastroscopy. Patients having a history of pill ingestion followed by retrosternal chest pain with GI symptoms of less than 10 days duration and having typical endoscopy findings like kissing ulcer, multiple small discrete ulcers or erosion of esophagus were diagnosed as PIO after excluding other oesophageal pathologies. RESULTS AND CONCLUSION: Among 1000 retrosternal chest pain patients, 450(45%) cardiovascular, 255(25.5%) respiratory, 248(24.85%) upper GI and 47(0.47%) had other system involvement. Among 248 GI patients, the frequency of symptoms was as follows: Pinpoint localized odynophagia (8.46%), non-localised odynophagia (12.09%), nausea (62.09%), vomiting (44.35%), dysphagia (3.62%), dyspepsia (13.70%) and hematemesis (0.8%). PLO, dysphagia, and hematemesis were significant symptoms of PIO (p<0.05). Endoscopic findings suggestive of PIO such as kissing ulcer, multiple small discrete ulcers, oesophageal erosions were observed in 91.30%, 47.83%, and 34.78% patients, respectively. Involvement of the middle third of esophagus was present in 74.19% and the lower third in 25.81% patients. Most of the patients with PLO had kissing oesophageal ulcer seen on endoscopy (pvalue =0.0002). The habit of consuming pill with less than 100 ml of water and consumption of night pill dose 10 minutes or less before sleeping were observed as significant risk factors for PIO (p value<0.05). PLO is a newly established and highly specific symptom of PIO of our study and it matches with kissing ulcer of the esophagus by endoscopy.