Background:Primary CNS Vasculitis (PCNSV) is an uncommon inflammatory condition selectively affecting blood vessels of the central nervous system and has diagnostic difficulties. Long term treatment outcomes are unclear.Objective:To elucidate the clinical progression and long-term outcomes of patients with biopsy proven PCNSV.Methods and Material:Clinical data of eight consecutive patients with PCNSV established by meningocortical biopsy were reviewed. Patients had undergone extensive evaluation for secondary causes.Results:The average age at presentation was 33.5 years (25 to 47 years). Three were females. The average follow-up period was 65 months (24 to 108 months). Clinical presentation included acute or subacute focal neurological deficits, seizures, headache and cognitive decline. MRI findings consisted of multifocal gray and white matter signal changes with microhaemorrhages. On contrast multifocal areas of enhancement affecting gray matter, white matter, vessel wall, dura and leptomeningeal areas were observed. Diagnostic yield of DSA was poor. Histopathology showed granulomatous angiitis in six and lymphocytic angiitis in two. Treatment protocols followed were similar for all patients: initial induction with intravenous methylprednisolone and cyclophosphamide, followed by maintenance immunosuppressants (with or without oral steroids). Disease control was reflected by significant improvement on MRI. Multiple clinical relapses occurred over the years (13 relapses, 0 to 4 per patient). Serial MRI studies helped detect subclinical disease activity. Treatment escalation aimed at achieving "no evidence of disease activity" helped in better disease control and remission in patients with active disease. Rituximab was useful in select cases to control disease activity and as rescue therapy (n = 3). Mean MRS score at last follow up was 0 or 1 (unchanged from baseline). Treatment complications included infections and avascular necrosis of hip (n = 1). One patient died due to severe COVID-19 pneumonitis.Conclusion:PCNSV has varied clinical presentation and diagnostic challenges. Immunosuppressive therapy is necessary and is effective but with associated risks. Histopathological confirmation helps to prognosticate and initiate early aggressive treatment for better results. Close clinico-radiological follow up and long-term immunotherapy to ensure disease remission can help manage these patients successfully.
Sir, The course of COVID-19 in the general population has varied from asymptomatic infection to severe disease and death. Risk factors for severe COVID-19 include underlying health conditions such as respiratory disease, cardiovascular disease, cancer, diabetes, hypertension, old age, obesity, and smoking.[1] Rituximab is an anti-CD20 B-cell monoclonal antibody that suppresses the humoral immune response by depleting the B-cells. It has been found effective in remitting-relapsing multiple sclerosis (RRMS) and useful in progressive MS. In this report, we describe a PwMS on rituximab therapy who contracted COVID-19 and went on to develop a prolonged course of disease due to persistent infection and possible reactivation. A 49-year-old gentleman with a history of secondary progressive MS had been on rituximab therapy for the last two and a half years. He had received a cumulative dose of 2.5 g of rituximab and the last dose was of 500 mg. Two months post infusion, he presented to the hospital with fever for two days and mild worsening of gait. On examination, his temperature was 100°F, oxygen saturation was 98%, and he had a spastic ataxic gait with mild dragging of his right foot while walking. He was tested for COVID-19 RT-PCR, which turned positive. Chest X-ray and routine blood parameters including ESR, CRP, and ferritin were normal while d-Dimer was marginally elevated (544.89 ng/ml). Considering his immunosuppressed state due to rituximab, he was hospitalized and treated with remdesivir for five days along with symptomatic measures. His fever abated and he was discharged home. He was doing well at home for 15 days. Subsequently, he developed recurrence of COVID-19 symptoms in the form of fever and cough. Gait worsened and his expanded disability status score (EDSS) increased from 3 to 6. He developed oxygen desaturation (SpO2: 94) on pulse oximetry. Repeat COVID-19 RT-PCR was negative. He was re-admitted and treated with antibiotics, antipyretics, methyl-prednisolone, and oxygen inhalation. CT scan [Figure 1a] done 23 days after the onset of initial symptoms showed features of COVID-19 pneumonia. He was discharged after seven days. Post discharge, he continued to have fever and cough and required oxygen support at home to maintain saturation. Because his symptoms persisted, CT thorax was repeated (day 35 from onset), which showed an increase in ground glass appearing shadows and features of new viral pneumonitic patches [Figure 1b]. RT-PCR for SARS-CoV-2 was repeated (day 37 from onset), which turned positive. CD-19 cells were undetectable and serum immunoglobulin level was 600 mg/dL (normal: 700–1600 mg/dL). He was treated with nintedanib, oral methylprednisolone along with inhalation bronchodilators, and budesonide. The positive RT-PCR was initially attributed to the presence of nonviable viral particles rather than persistent infection, and because fever persisted, steroids were continued. He was given paracetamol, mefenamic acid, and naproxen for fever. In spite of these, he continued to have intermittent fever and cough. Therefore, CT thorax was repeated (day 77 from onset), which showed resolution of some lesions but development of new lesions consistent with recurrent viral pneumonia [Figure 1c]. RT-PCR for SARS-CoV-2 from the nasopharynx was negative. However, bronchoalveolar lavage was not done. Considering the possibility of viral reactivation/persistence, he was given a course of favipiravir, which rendered him afebrile and free of respiratory symptoms.Figure 1: Timeline depicting the course of the disease. EDSS: expanded disability status score, RT-PCR: real-time polymerase chain reaction, Up arrow indicates an increaseAt the last follow-up, four months after the onset of initial infection, he is ambulant, has an EDSS of 4, and is independent. The course of the disease is shown in Figure 1. His serial CT scan findings are shown in Figure 2, and the laboratory findings are shown in Table 1.Figure 2: Serial CT findings through the course of illness. Serial CT scans taken throughout the course of the illness, showing progressive changes. Images represent the upper zone (1), carina (2), bronchial bifurcation (3), and right hemidiaphragm (4). (A) CT scan taken at day 23 showing peripheral-based consolidations (arrows) in the lower lobes bilaterally involving the subpleural regions (A4). (B) CT scan taken at day 35 showing new consolidations (arrows) in the left upper lobe with partial resolution of the lower lobe opacities (B4). Left-sided small pleural effusion can also be appreciated. (C) CT scan taken at day 77 showing new consolidations (arrows) in right upper (C1) and left lower lobes (C4). Left upper lobe consolidation shows significant resolutionTable 1: Laboratory FindingsCOVID-19 outcomes in PwMS receiving rituximab have been variable and conflicting, ranging from mild disease to severe disease and death. Initial reports on COVID-19 in PwMS receiving rituximab did not suggest adverse outcomes.[2,3] Patients treated with anti-CD20 agents were found to have adequate resolution of COVID-19 despite undetectable antibodies against SARS-CoV-2, suggesting limited role of humoral immunity in determining outcomes.[4] There have even been arguments for a beneficial and protective effect of immunosuppressive and anti-CD20 therapies in COVID-19.[5] However, several other reports have associated rituximab with severe COVID-19. In a pooled analysis of 2493 subjects with demyelinating disorders who contracted COVID-19, a mortality of 4% was observed among 113 of these subjects who received rituximab.[6] Langer-Gould et al.[7] reported increased risk for hospitalization with rituximab, suggesting more severe disease. Our case had prolonged COVID-19. After recovery from an initial mild infection, the symptoms recurred and persisted for almost 3 months. His RT-PCR, which had turned negative again, became positive along with persistent symptoms. There could be pitfalls in the nasopharyngeal RT-PCR sensitivity and nonviable viruses could yield positive test. This was our assumption when the second RT-PCR turned negative and the third became positive. However, serial CT scan changes suggested recurrent viral pneumonia. Conditions such as bronchiolitis obliterans with organizing pneumonia and rituximab-induced lung disease were other differentials but were unlikely in the setting of ongoing steroid therapy. Persistence of COVID-19 symptoms, positive SARS-CoV-2 RT-PCR, and radiological appearance favoring viral pneumonia support the possibility of viral reactivation. Moreover, he was rendered asymptomatic only after another course of anti-viral therapy with Favipiravir after the failure of multiple antipyretics and steroids. This again suggests that there was persistent viral infection in our case and also a beneficial role of Favipiravir in COVID-19. Rituximab is known to induce replication and reactivation of viruses such as cytomegalovirus, herpes simplex virus, varicella-zoster virus, and West Nile virus.[8-10] Rituximab has been associated with prolonged COVID-19 course, with persistent fever lasting for more than a month, delayed worsening after an initial recovery, prolonged pneumonia, and poor production of anti-SARS-CoV-2 antibodies.[9,11-13] Bose et al. reported a case of rituximab-induced reactivation of COVID-19 3 weeks after initial infection.[10] Production of antibodies against SARS-CoV-2 was inadequate in our case (0.03 U/ml at 10 weeks) despite prolonged infection, which was likely a contributory factor for the protracted course of infection. Our patient was also receiving oral steroids. As RT-PCR can remain positive for up to 10 weeks after infection, the positive RT-PCR was erroneously attributed to prolonged noninfectious shedding of viral particles rather than persistent infection. Therefore, steroids were continued assuming that the cause of fever was inflammatory rather than due to infection. Co-prescription of steroids could have been another contributory factor for prolonged disease in our case. In prolonged viral infections, the continuous presence of the viral antigen renders virus-specific T-cells to become dysfunctional.[14] Moreover, rituximab is also known to affect CD 20+ T-cells.[15] Our case confirms the risk of rituximab-induced prolonged and severe COVID-19 and the possibility of reactivation of SARS-CoV-2. The initial clinical course of COVID-19 in patients receiving rituximab could be misleadingly mild. Patients on rituximab who contract COVID-19 must be closely monitored for persistent infection and possible reactivation. We suggest caution in using steroids in such situations. In case of prolonged COVID-19 symptoms in persons on rituximab, reactivation of SARS-CoV-2 should be considered and anti-viral therapy repeated. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
Introduction: Comorbidities frequently accompany psoriasis and psoriatic arthritis (PsA) and add to the disease burden. We aimed to identify the comorbidity burden in patients with PsA and evaluate its impact on the disease activity measures in our geographic region. Methods: This was a multicenter, cross-sectional study involving consecutive PsA patients from 17 rheumatology centers. Their disease variables and comorbidities were recorded. Results: In 549 enrolled patients, the mean age was 39.2 (14.9) years, with male predominance (6:5). The mean duration of PsA was 63.1 (76.3) months and 232 (42.3%) patients had one or more comorbidities. Dyslipidemia was the most prevalent comorbidity, followed by hypertension (HTN) (19.8%) and diabetes (16.6%). About 39% of patients were overweight and 18% were obese. Smoking, ischemic heart disease, hypothyroidism, osteoarthritis, depression, anxiety, and fractures were seen in <5% of the cohort. Increasing age, longer duration of psoriasis, a family history of cardiovascular disease (CVD) or stroke, smoking, alcohol consumption, and higher waist circumference were associated with the presence of one or more comorbidities. Overall, 104 (18.9%) patients needed hospitalization for various comorbidities. Infections accounted for 59 (10.8%), of which skin (23) was the most common site, followed by urinary tract (6) and lung (4). Conclusions: More than 40% of PsA patients have comorbidities. Dyslipidemia, HTN, diabetes, and obesity were most prevalent, putting these patients at risk for CVDs. Active screening for these comorbidities is crucial for providing comprehensive care to these patients.
Introduction: Psoriatic arthritis (PsA) is a chronic inflammatory disease with significant functional impairment. Health Assessment Questionnaire-Disability Index (HAQ-DI) is a reliable and validated outcome measure for a variety of arthritides including PsA. Objective: The objective of this study was to assess the disability as an outcome measure in PsA using the Indian version of HAQ (I-HAQ). Methods: The I-HAQ was administered to PsA patients diagnosed as per the Classification Criteria for PsA. The I-HAQ comprises 12 questions (nine basic and three advanced activities of daily living (ADLs), on the standard HAQ format) relevant to the Indian population. Results: In the 549 participants, the mean I-HAQ was 0.31 (0.45) and 48.2% had mild-to-moderate disability (I-HAQ>0–1). Female gender, older age, higher skin, joint scores, and Disease Activity Index for PsA were associated with some disability (I-HAQ>0). Symmetric polyarthritis (0.34) and spondyloarthritis (0.32) had a significantly higher disability compared to other subsets. Analyzing the individual questions of I-HAQ, squatting in the toilet or sitting cross-legged on the floor (r = 0.78), walking 3 km (r = 0.77), and climbing a flight of stairs (r = 0.74) correlated maximally to the total I-HAQ. ADL which was affected most frequently was “climbing a flight of stairs.” I-HAQ was significantly lower in patients who had been on disease-modifying antirheumatic drugs for 6 months or more (P = 0.0001). Conclusions: The Indian version of HAQ-DI could be efficiently employed to assess outcomes in our cohort. Nearly half of the cohort had mild-to-moderate disability suggesting a high burden of inflammation. Higher joint activity scores are strongly associated with disability.
Angioedema is defined by World Allergy Organization as a transient swelling of the skin or submucosal surface due to increased vascular permeability of small venules. Most common etiologies include IgE-mediated allergic reactions (to food, drug, or environmental triggers), nonsteroidal anti-inflammatory drug (NSAID), and chemically induced histamine release (most commonly opiates, highly cationic antibiotics, and muscle relaxants). Recent publications show a global incidence of anaphylaxis between 50 and 112 episodes per 100 000 person-years while the estimated lifetime prevalence is 0.3-5.1%. Timely intubation and administration of steroids/ antihistaminic agents will prevent a catastrophic cannot intubate cannot ventilate situation. In small, resource limited environment of a field hospital which may be compared to a rural setting in India managing such emergencies is challenging. If available in a case of anticipated difficult airway like this difficult airway cart must contain a whole armamentarium of airway adjuncts and gadgets. History of consumption of fish (Nile Perch) a rare form of allergen causing airway and breathing issues leading to timely intubation saved the life of patient.
