Jehad Azar

Hot tub lung (HTL) is a rare granulomatous pneumonitis caused by inhalational exposure to Mycobacterium avium complex (MAC)‐contaminated hot tub water, with debated pathogenesis encompassing both hypersensitivity and infectious mechanisms. A 66‐year‐old woman with progressive exertional dyspnea was initially misdiagnosed with non‐fibrotic hypersensitivity pneumonitis attributed to pheasant exposure and treated with corticosteroids and mycophenolate without improvement. High‐resolution CT demonstrated diffuse centrilobular nodules with air‐trapping. Surgical lung biopsy revealed bronchiolocentric non‐necrotizing granulomas with rare MAC organisms despite negative bronchoalveolar lavage cultures. Detailed clinical history disclosed daily indoor hot tub use coinciding with symptom onset. Following hot tub cessation and initiation of azithromycin, ethambutol and rifabutin, she ultimately achieved complete clinical and radiologic resolution. HTL represents a heterogeneous spectrum from immune‐mediated hypersensitivity to true mycobacterial infection. Persistent interstitial lung disease despite ongoing immunosuppression should prompt a thorough hot tub exposure history and selected patients may require antimycobacterial therapy alongside exposure cessation.

Introduction and importance: Kaposi sarcoma (KS) is an angioproliferative disease, that mostly affects HIV-infected patients with a high viral load and a low CD4 count. In rare cases, the paradoxical worsening of a pre-existing or previously unrecognized opportunistic infection occurs in a phenomenon known as immune reconstitution inflammatory response (IRIS). Case presentation: The authors presented a male patient in his 30s with HIV, who developed a series of complications caused by KS following the initiation of antiretroviral therapy. Despite ongoing antiretroviral therapy (ART), chemotherapy, and supportive measures, the patient developed KS-related IRIS, characterized by rapid clinical deterioration, multiorgan failure, and ultimately succumbed to the disease. Clinical discussion: To the best of our knowledge, very rare cases have been reported with KS-IRIS after the initiation of ART. Many predictors of KS-IRIS development have been identified. Patients must meet the known diagnostic criteria to be diagnosed with IRIS. The treatment of KS-IRIS depends on the stage of KS. ART alone is usually adequate in mild cutaneous KS. Chemotherapy and ART are recommended for patients with severe cutaneous and visceral KS. Conclusion: HIV patients with KS undergoing ART initiation or modification should be closely monitored, particularly during the early stages and in those with extensive disease. Treating opportunistic infections before ART initiation may reduce the risk of KS-IRIS. The increasing prevalence of KS in ART-treated patients with HIV warrants further attention and highlights the need for better management strategies in this population.

Introduction and importance: Brentuximab vedotin (BV) is an anti-CD30 antibody approved for various cancers, including refractory Hodgkin lymphoma (HL), anaplastic large-cell lymphoma (ALCL) among others. In general, BV has been found to be well-tolerated, with the most frequently reported side effects being peripheral neuropathy and neutropenia. BV-induced pneumonitis is extremely rare. To the best of our knowledge, this is the sixth reported instance of BV-induced lung toxicity. Case presentation: This case presents a female patient in her forties diagnosed with cutaneous T-cell lymphoma undergoing BV treatment. She developed acute hypoxic respiratory failure, ultimately, underwent a diagnostic evaluation including a computed tomography (CT) scan, which showed bilateral airspace consolidations and ground-glass opacities, suggestive of organizing pneumonia and diffuse alveolar damage. Bronchoscopy with bronchoalveolar lavage and transbronchial biopsy ruled out infection, and pulmonary lymphoma and confirmed the diagnosis of BV-induced pneumonitis. The patient had significant clinical improvement after stopping the offending agent, and starting steroids, with optimal clinical recovery at 8 weeks follow-up. Clinical discussion: Drug-related pneumonitis poses a significant concern in the management of cancer patients. Numerous chemotherapeutic agents, such as bleomycin, cyclophosphamide, methotrexate, thalidomide, and others, have been associated with pulmonary-related toxicities. These adverse effects primarily stem from direct toxicity or immunosuppression-related infections. Less commonly, immune-mediated injury may occur. Conclusion: Physicians must have a high index of suspicion for BV-induced pneumonitis, hence, early recognition with subsequent holding of the causative agent, initiation of immunosuppression with steroids, and occasionally steroid-sparing medications, prevent an otherwise fatal outcome.

Introduction and importance: Birt-Hogg-Dube (BHD) is a rare genetic disorder that results from a mutation in the folliculin (FLCN) gene. Manifestations include pulmonary cysts, fibrofolliculomas, renal tumors, and pneumothoraces. Genetic testing can be used to confirm the diagnosis when suspected. BHD syndrome is diagnosed in patients with negative FLCN gene results using diagnostic criteria. Case presentation: A male in his 20s presented with recurrent pneumothoraces. A physical examination revealed bumps on his face and upper body. A chest computed tomography scan revealed cystic lesions. Blood tests, ESR, and CRP levels were unremarkable. Punch skin biopsy revealed fibrofolliculomas. Genetic testing for the FLCN mutation returned negative. His history, physical exam, imaging, and histopathology suggested BHD syndrome despite having a negative family history and genetic analysis. Eventually, the patient was diagnosed with FLCN gene-negative BHD syndrome. Clinical discussion: More than a hundred families have been identified to have BHD worldwide. There are a few cases in the literature describing patients phenotypically presenting with BHD despite having a negative genetic analysis. One study in Japan found 16 out of 157 individuals having a clinical presentation of BHD with no mutations. Also, decreased expression of the FLCN mRNA may lead to BHD. Conclusion: BHD syndrome can present with a negative FLCN gene mutation; however, patients must meet the known diagnostic criteria such as criteria made by Menko et al., Gupta et al., and Schmidt et al. in order to have a diagnosis of BHD syndrome. Also, a qualitative decrease of FLCN with the absence of mutations may also lead to BHD.

Pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary vasculature that results in precapillary pulmonary hypertension. PAH is caused by a group of clinical conditions involving multiple organ systems. Several cases have been reported in the literature demonstrating an association between vitamin C deficiency and PAH. Low endothelial nitric oxide levels in the pulmonary vasculature, combined with the inappropriate activation of hypoxia-inducible transcription factors, seen in patients with ascorbic acid deficiency, are believed to be the main contributors to the pathogenesis of pulmonary vasculopathy and the exaggerated pulmonary vasoconstrictive response seen in patients with scurvy-induced PAH. Vitamin C supplementation is considered the definitive treatment.

Parkinsonism-hyperpyrexia syndrome (PHS) is a rare, potentially fatal neurological emergency, that is seen in Parkinson’s Disease (PD) patients and mimics neuroleptic malignant syndrome. The most common trigger for PHS is sudden withdrawal of anti-parkinsonian medications, specifically levodopa. However, it can also be due to Deep Brain Stimulation (DBS) device malfunction. In this work, we describe three cases of PHS; the first of which is related to DBS battery depletion, and the remaining two to dopaminergic withdrawal. Additionally, we will include the results of a literature review on PHS, its etiologies, presentation, and management.

Parkinsonism-hyperpyrexia syndrome (PHS) is a neurologic potentially fatal emergency that mimics neuroleptic malignant syndrome. It commonly presents as systemic inflammatory response syndrome, acute onset worsening of muscular rigidity, autonomic instability, hyperpyrexia, confusion, diaphoresis and high creatine phosphokinase. The most common trigger for PHS is reduction or withdrawal of anti-Parkinson’s medications, especially levodopa. It was also reported in a few cases following deep brain stimulation of the subthalamic nucleus surgery shortly after anti-Parkinson’s medications were discontinued. Rare causes of PHS include deep brain stimulator (DBS) malfunction due to battery depletion. To the best of our knowledge, PHS following DBS battery depletion was reported only in three occasions. Here, we report a case of PHS due to DBS battery depletion presented as sepsis and was successfully treated with the administration of dopamine agonists, intravenous fluids and changing the DBS battery.

Pulmonary arterial hypertension (PAH) describes a rare, progressive disease of the pulmonary vasculature, involving a group of clinical conditions that result in precapillary pulmonary hypertension (PH). PAH is characterized by proliferative vasculopathy, and subsequent right heart failure. For the past several decades research has focused on identification of underlying molecular causes of this disease. Recently, there have been a number of reported cases of patients with scurvy developing pulmonary arterial hypertension. Thus, it has been hypothesized that vitamin C deficiency results in non-hypoxic activation of hypoxia inducible transcription factors (HIF) and low nitric oxide (NO) level in the pulmonary vasculature, leading to subsequent pulmonary vasculopathy and an exaggerated pulmonary vasoconstrictive response. Immediate supplementation of vitamin C is considered the definitive treatment, preventing an otherwise fatal outcome. In this paper, we describe a patient with a fatal case of scurvy related PAH, who was admitted with ecchymosis, oral ulceration, and dyspnea.

Stress (Takotsubo) cardiomyopathy (CM) is defined as a transient regional systolic dysfunction of the left ventricle that mimics acute coronary syndrome (ACS) in the absence of significant coronary artery disease or plaque rupture. This phenomenon commonly occurs in postmenopausal females in the presence of emotional, physical and psychological stressors with excess catecholamine stimulation, resulting in diffuse microvascular spasm and subsequently myocardial stunning. Here we report a 58-year-old postmenopausal female patient with end stage renal disease (ESRD) who was presented to our hospital with a clinical picture suggesting ACS. Shortly after admission she progressed to cardiogenic shock and pulseless electrical activity (PEA) and was diagnosed retrospectively with Takotsubo cardiomyopathy. She was successfully treated with beta-blockers, IV fluids and inotropic agents. Intra-aortic balloon pump (IABP) was considered, however, the patient gradually improved to full recovery with resolution of left ventricular function back to normal.