Should Histoplasmosis be Screened for Before Initiation of Tumour Necrosis Factor Alpha Inhibitors?

Histoplasmosis is a soil-based dimorphic fungus endemic to the Midwest and Southeastern United States and is responsible for infection through inhalation of conidia. Infection is usually asymptomatic, as the fungal growth is contained by formation of granulomas. However, dissemination can occur in immunocompromised hosts due to the lack of optimal activity of interferon gamma, tumour necrosis factor alpha (TNF-alpha) and interleukin-17. There is a significant overlap between the symptomatology of histoplasmosis and granulomatosis with polyangiitis (GPA). We report a case of a 48-year-old female who presented with high-grade fever, worsening generalised weakness and tachycardia. She had a previous history of bilateral cavitary lung lesions for which she was evaluated at an outside facility. As her entire infectious investigation was negative and found to be positive for antineutrophil cytoplasmic antibody (ANCA), a diagnosis of GPA was made, and she was initiated on rituximab infusions 7 weeks prior to her presentation to our facility. Repeat infectious investigations at our facility were positive for (1-3)-ß-D-glucan test and urine histoplasma antigen. Prompt discontinuation of rituximab and initiation of systemic antifungal therapy led to clinical improvement. Based on this experience, we highlight the association of histoplasma with ANCA positivity along with the importance of closely monitoring these patients for possible clinical worsening after the initiation of TNF-alpha inhibitors, despite the negative infectious work-up. Also routine screening or pre-emptive therapy for histoplasmosis before the initiation of TNF-inhibitors is not recommended. LEARNING POINTS: Histoplasmosis is associated with ANCA positivity.Despite the negative investigations for histoplasmosis and criteria for GPA being met, patients should be closely monitored for possible clinical worsening after the initiation of immunosuppressive therapy, especially TNF-alpha inhibitors.Current guidelines are not recommending routine screening or pre-emptive therapy for histoplasmosis before initiation of TNF-alpha inhibitors.

Mixed Plate Ductal Intrahepatic Cholangiocarcinoma Mimicking Hepatocellular Carcinoma.

Cholangiocarcinoma (CCA) refers to malignancies of the bile ducts that arise in the intrahepatic, perihilar, or distal (extrahepatic) biliary tree, excluding the gallbladder and ampulla of Vater. Although rare, the majority of these cancers are locally advanced at presentation, making them extremely fatal. We present a case of a 65-year-old man who came in for abdominal pain and ascites and was found to have portal vein thrombosis. Initial imaging showed a hepatic lesion, raising suspicion of a hepatic malignancy. Despite the multiple imaging modalities used, the diagnosis remained uncertain. Eventually, a biopsy of the lesion showed it to be a variant of intrahepatic CCA, which has mixed features of hepatocellular carcinoma and CCA. This variant is highly malignant and poorly responsive to treatment, leading to a poor prognosis. Our patient on diagnosis was categorized as stage 4 cancer, and although treatment was initiated, she succumbed to the disease in six months. Based on our experience with this patient, we would like to highlight the significance of a multimodal imaging approach and the necessity of tissue diagnosis when the initial work-up is inconclusive since these factors will also impact the course of management.

Neonatal Purpura Fulminans in a Patient With Arterial Thrombosis and Congenital Renal Agenesis.

Neonatal purpura fulminans (PF) is an uncommon skin disorder characterized by acute disseminated intravascular coagulation, tissue necrosis, and small vessel thrombosis. Here, we present a case of a seven-day-old male who was admitted to the Neonatal Intensive Care (NICU) Unit at Gaafar Ibn Auf Tertiary Hospital, in January 2023. He presented with black bullous lesions on the plantar surface of the left foot, deep bluish discoloration over the right buttock and right lower abdomen, and gangrenous changes in the right foot with clear demarcation. Birth history was not significant other than mild pallor and icterus. His blood workup was consistent with severe anemia, thrombocytopenia, elevated prothrombin time, and partial thromboplastin time with decreased protein C and S levels; blood culture yielded no growth. A Doppler ultrasound scan of lower extremities confirmed distal occlusion of the right dorsalis pedis artery. The abdominal ultrasound revealed a free left renal bed and left-sided renal agenesis. We came to a diagnosis of neonatal PF and started administering blood and fresh frozen plasma and subcutaneous heparin injections, but unfortunately, the patient eventually passed away. Hence, we decided to report this case to emphasize the significance of the clinical picture in assisting with early diagnosis, despite limited access to genetic testing. We also want to highlight the importance of a "high index of suspicion" that might be mandatory for better outcomes.

Latent Autoimmune Diabetes in Adults and a Continuous Glucose Monitoring Device: An Unfortunate Outcome.

Latent autoimmune diabetes in adults (LADA) is a slow-progressing form of autoimmune diabetes. A 44-year-old man with a four-year history of diabetes mellitus (DM), obsessive-compulsive disorder (OCD), and panic disorder was admitted to the hospital for diabetic ketoacidosis. LADA was confirmed with positive GAD-65 antibody. His occupation involved random working days with several weeks off in between projects. During workdays, his insulin dosage required frequent adjustments due to lower blood glucose (BG) readings. Owing to the variable work schedule and constantly changing insulin needs, he was recommended a continuous glucose monitoring (CGM) device. Few days after starting on the CGM device, he was seen in the emergency department because of elevated BG. His home BG readings ranged from 80 to 408 mg/dL. He was getting frustrated with the fluctuating BG readings. At home, he remained agitated and endlessly checked his CGM device. After discharge, he would repeatedly call the endocrinology office with his BG readings with the insulin dose being adjusted accordingly. Few weeks later, the office received a call from his wife informing us that the patient had shot himself in the head. According to his wife, lately he had trouble sleeping, was very anxious, and often had panic attacks. He seemed to struggle with ever-fluctuating BG readings and was obsessed with incessantly changing numbers on his CGM device. Patients with Type 1 DM are at increased risk of mental health disorders and suicide forms a sizeable proportion of deaths in these patients. This case highlights the importance of mental health, especially underlying OCD as a prognostic factor in the management of diabetes with CGM devices.

Triple Vessel Coronary Artery Disease Identified in a 21-Year-Old Female.

Premature coronary artery disease (CAD) is characterized by the presence of symptomatic atherosclerosis in the coronary circulation in males below the age of 55 and females below the age of 45. We present the case of a 21-year-old female with a past medical history of heart failure with preserved ejection fraction, poorly controlled diabetes mellitus, essential hypertension, nephrotic syndrome, dyslipidemia, and class I obesity who presented with complaints of worsening bilateral lower extremity edema and exertional shortness of breath. Given her physical examination findings and laboratory investigations, a diagnosis of heart failure exacerbation was made. Echocardiography revealed a significant change in ejection fraction from three months earlier, and thus, she underwent a nuclear stress test. She was found to have fixed perfusion defects in the inferior wall. A diagnostic left heart catheterization identified severe triple vessel disease affecting the left anterior descending, left circumflex, and right coronary arteries. The patient and her family opted against coronary artery bypass grafting, and she was discharged to pursue high-risk intervention as an outpatient. This case highlights the importance of strict regulation of modifiable risk factors for CAD even in teenagers and young adults as her disease process likely began several years prior to the ultimate development of triple vessel CAD.

Right atrial thrombus leading to pulmonary embolism in a patient with dermatomyositis and COVID-19 managed with FlowTriever device thrombectomy.

A woman in her late 40s presented with complaints of shortness of breath, right-sided pleuritic chest pain and diffuse myalgias. She was diagnosed with deep vein thrombosis (DVT) 3 weeks earlier and had been compliant with her oral anticoagulation therapy. Investigations revealed a pulmonary embolism (PE) involving the right distal pulmonary artery on a CT angiogram of the chest. She was also found to have an incidental SARS-CoV-2 (COVID-19) infection and an elevated creatine kinase value. Anticoagulation with intravenous heparin was initiated according to the DVT/PE protocol. The following morning, a medium-sized mobile mass was identified in her right atrium on performing a transthoracic echocardiogram. Due to concerns of embolisation of the mass which could result in obstruction, right ventricular strain and ultimately haemodynamic instability, a thrombectomy was performed using the FlowTriever device under transthoracic echocardiography guidance. The right atrial mass was successfully removed and the patient was transitioned to another oral anticoagulant agent. On discharge, a muscle biopsy was performed and aided in the diagnosis of dermatomyositis and the patient received intravenous Ig, steroids and methotrexate.

A Case of Acute Extensive Viral Sinusitis Secondary to Acute Epstein Barr Virus.

Infectious mononucleosis (IM), the most common presentation of acute Epstein Barr virus (EBV) infection, typically presents with fever, pharyngitis and lymphadenopathy. We describe an unusual case of IM presenting as acute sinusitis. A 25 year-old male presented to the emergency department with worsening right frontal sinus pain along with fever, chills, and greenish nasal discharge for 3 weeks. Laboratory workup showed leukocytosis with high lymphocyte counts as well as transaminitis. Facial computerized tomography (CT) showed extensive right frontal, ethmoidal and maxillary sinusitis and antrochoanal polyp. The patient underwent endoscopy with drainage of purulent material and polyp removal. Unfortunately, cultures of the sample were not sent and bacterial infection could not be ruled out. Broad spectrum antibiotics were continued. Pathology of redundant tissue revealed large atypical lymphocytes with positive EBV-encoded RNA and lack of evidence of extranodal natural killer/T-cell (NK/T-cell) type lymphoma (ENKTCL). Tests for serum EBV IgM antibodies and EBV early Antigen antibodies were positive, indicating acute EBV infection. Lymphocytosis resolved along with significant clinical improvement at the 10-day follow up visit. Even though patient did receive antibiotics, multiple factors including isolated lymphocytosis, pathology positive for EBV with no neutrophilia were more suggestive of sinusitis caused by viral infection, EBV in this case. Lymphocytosis with fever and sore throat should prompt physicians to consider IM. There are no known reports in the literature of EBV as a causal organism for acute viral sinusitis. There are some studies relating EBV with ENKTCL. It is unknown whether this particular patient with a history of EBV sinusitis will be at high risk for nasal type lymphoma in the future. Further studies should be conducted to understand the pathogenesis and relationship between EBV and ENKTCL. LEARNING POINTS: Infectious mononucleosis (IM) can present with various atypical presentations. Consideration of IM should not be limited to people presenting with a triad of fever, lymphadenopathy and sore throat. Lymphocytosis with atypical symptoms should raise suspicion of infectious mononucleosis.No case has been reported of EBV as a causal organism for acute sinusitis. Association with EBV infection and chronic sinusitis or nasal polyp or extranodal NK/T cell lymphoma has been demonstrated but pathogenesis is poorly understood.Studies should be done on whether acute sinusitis secondary to EBV poses a risk for nasal type lymphoma.

Secukinumab-Induced Crohn's Disease in a Patient Treated for Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis (JIA) is a common form of arthritis that occurs in children, typically with an onset before the age of 16 years. It can affect joints in any part of the body. As per the International League of Rheumatology, JIA is classified into systemic arthritis, oligoarthritis, extended oligoarthritis, polyarthritis (rheumatoid factor positive), polyarthritis (rheumatoid factor negative), enthesitis-related arthritis (ERA), juvenile psoriatic arthritis (JPsA), and other arthritis. JIA is treated with disease-modifying antirheumatic medications (DMARDs), which include both nonbiologic agents like methotrexate (MTX) and biologic agents like inhibitors of tumor necrosis factor-alpha, interleukin-1 (IL-1), IL-6, and T-cell co-stimulation modulators. As per recent studies, in December 2021, Secukinumab, an IL-17A inhibitor, is one of the most recent biologic agents approved for active ERA and JPsA. A few reports have suggested Secukinumab is related to new-onset inflammatory bowel diseases (IBDs). We present a case of a 20-year-old female who was being treated with Secukinumab for JIA, and six months into therapy, she developed symptoms suggestive of Crohn's disease (CD). The diagnosis was confirmed with colonoscopy, histopathology, and radiology results. Her symptoms completely resolved four weeks after discontinuing Secukinumab and oral steroid therapy. The efficacy and side effects of Secukinumab have been studied mainly on middle-aged populations who were being treated for psoriasis and ankylosing spondylitis (AS); however, there is limited literature on younger populations. With this case report, we would like to highlight the possible relationship between the development of IBD and Secukinumab therapy in the adolescent population and emphasize the importance of regular screening for IBD in this population.

A Case of Severe Cardiomyopathy Due to Covid-Induced Myocarditis, Completely Resolved after Colchicine and Immunoglobulin Therapy.

Coronavirus 19 (COVID-19) is well known for causing acute respiratory distress syndrome. Among other systemic complications, myocarditis is a frequently reported presentation as well as complication. One systematic review reported a 14% mortality rate in patients with COVID-19 myocarditis. Endomyocardial biopsy is a definitive diagnostic test but has been a challenge to perform in most cases of COVID myocarditis due to the contagious nature of the disease. Patients presenting with new cardiomyopathy with troponin leak and arrhythmias, supported by recent COVID-19 diagnosis should be suspected for COVID-induced myocarditis. Supportive treatment has been the mainstay of treatment with limited data on immunotherapy and colchicine. Our case is about a male in his 50s who had a cardiac arrest due to ventricular fibrillations, with a positive COVID-19 test. Further workup showed severe non-ischaemic cardiomyopathy with an EF of 15-20%. He was treated with intravenous immunotherapy and colchicine. A repeat echocardiogram 3 days later showed resolution of cardiomyopathy. Our case report highlights the possible beneficial effects of immunotherapy and colchicine in viral myocarditis. LEARNING POINTS: Myocarditis should be suspected in patients with acute onset cardiomyopathy with troponin leak and no evidence of ischaemia. COVID-19 myocarditis can present with arrhythmia, which could be fatal in some cases.Even though supportive management is the mainstay of treatment for COVID-19 myocarditis, there have been reports of benefits of intravenous immunotherapy (IVIG) and colchicine.More studies are warranted to explore the beneficial effects of IVIG and colchicine not just in COVID-19 myocarditis, but also in other viral causes of myocarditis he aim of this study is also to raise awareness among healthcare professionals about the Bentall procedure in patients with type A aortic dissection involving the aortic valve.

A Rare Presentation of Myositis and Diffuse Alveolar Hemorrhage Associated With Disseminated Cryptococcus neoformans Infection.

Cryptococcosis is a fungal infection caused by species of the Cryptococcus genus which are commonly found in soil contaminated with bird feces, decaying wood, and tree hollows. It is usually seen in immunocompromised patients such as those with AIDS, with hematological malignancy, on immunosuppressive therapy, or after organ transplantation, and rare in immunocompetent hosts. The primary site of infection is usually the lung and the infection starts after inhalation of the pathogen and depending upon the host's immune response shows a different pattern of infection. Here we present a case report of a female in her late forties, who presented with two weeks of rash in her bilateral upper extremity, lower extremity, chest, and back along with arthralgia, myalgia, and proximal lower extremity weakness. Initial laboratory workup showed leukocytosis, elevated erythrocyte sedimentation rate, C-reactive protein, serum ferritin, and serum aldolase level with normal creatinine kinase. Rheumatological workups including ANA, ANCA, RF, C3, and C4 were normal. Magnetic resonance imaging of the right femur showed hyperintensity of the thigh and proximal calf musculature suggestive of muscle edema. A punch biopsy from the rash showed dyskeratosis with mild perivascular neutrophilic infiltrate. Steroid therapy and rituximab were started with some improvement. However, the patient developed respiratory distress and diffuse alveolar hemorrhage. Bronchoscopy was done and bronchoalveolar lavage fluid grew Serratia and Candida. The patient improved with antibiotic and antifungal therapy. However, the patient again developed respiratory distress and a new diffuse alveolar hemorrhage. A repeat bronchoscopy was done and the new bronchoalveolar lavage grew Cryptococcus neoformans. Blood cultures also grew Cryptococcus neoformans. The patient was started on amphotericin B and flucytosine. The patient initially improved and was transferred to the rehabilitation unit but ultimately her course was complicated by multiple infections and intubations and she unfortunately passed away.