Guselkumab-Associated Pulmonary Disease and Diffuse Alveolar Hemorrhage with Drug Rash with Eosinophilia and Systemic Symptoms.

Psoriasis is a common skin condition worldwide. Moderate-to-severe disease is treated with biologic or non-biologic disease-modifying anti-rheumatic drugs. These include tumor necrosis factor (TNF)-a inhibitors, interleukin (IL)-17 inhibitors, and IL-23 inhibitors. Case reports of inhibitors of TNF-a and IL-12p40 subunits causing interstitial pneumonia (IP) have been published in the literature, but no case of anti-IL-23p19 subunit biologics causing IP and acute respiratory distress syndrome (ARDS) has been reported before. We report a case of a patient with restrictive lung disease secondary to a body mass index of 36.54 kg/m2, obstructive sleep apnea, and psoriasis, who developed IP and ARDS presumed to be secondary to guselkumab, an anti-IL-23p19 subunit monoclonal antibody. He was on ustekinumab, an anti-IL-12/23p40 for the treatment of psoriasis, but was switched to guselkumab eight months before the presentation, and since then he had been complaining of progressive shortness of breath. He initially presented to the hospital after having drug reaction with eosinophilia and systemic symptoms (DRESS) after being started on amoxicillin for a tooth infection. He was treated with high-dose intravenous steroids but developed progressive shortness of breath. Broad-spectrum antibiotics were added. An extensive infectious, autoimmune, and hypersensitivity work-up was undertaken, which returned negative. A bronchoscopy with bronchoalveolar lavage was performed, which revealed diffuse alveolar hemorrhage (DAH). His lung imaging and oxygenation progressively got worse; hence, no lung biopsy was taken. He was intubated and required inhaled nitric oxide, but due to the lack of improvement, the family elected for comfort measures, and the patient was extubated and passed away. To our knowledge, this is the first case of an association between guselkumab, IP, ARDS, and DAH. Rare instances of DAH with DRESS have been reported before. Whether it was DRESS or guselkumab that caused DAH was uncertain in our patient. Clinicians should monitor for DAH and shortness of breath in patients on guselkumab so that more data can be obtained and studied in the future.

Acute Respiratory Distress Syndrome Secondary to Enterovirus-Human-Rhinovirus Infection in an Adult.

Enterovirus-human-rhinovirus (EV-HRV) are small RNA viruses that are airborne and can spread by direct contact or fomites and usually cause the common cold, asthma and chronic obstructive pulmonary disease exacerbation. EV-HRV-associated acute respiratory distress syndrome (ARDS) is common in children but is a rare cause of ARDS in adults. ARDS is defined according to the Berlin criteria and can be mild, moderate or severe depending on the PaO 2 to FiO2 ratio. We report a case of a 70-year-old female with cardiac comorbidities, emphysema, second-hand smoking of 25 years, on methotrexate for rheumatoid arthritis presenting with ARDS secondary to EV-HRV infection. Despite initial treatment with appropriate antibiotics, steroids, low tidal volume mechanical ventilation, rescue maneuvers such as ventilation in prone positioning, paralyses, and inhaled nitric oxide, she passed away. EV-HRV causes upper respiratory tract infections but causes cytokine releases such as IL-1, IL-6, and IL-8 in the lower respiratory tract and in the blood which can cause ARDS. Very few cases of EV-HRV ARDS in immunocompetent adults are reported in the literature. Female sex is also associated with EV-HRV ARDS. No antiviral therapy exists for patients critically ill with EV-HRV; however, one case of successful treatment with high-dose intravenous vitamin C (HIVC) is reported in the literature. EV-HRV is one of the most common viruses identified in patients admitted with viral pneumonia in the intensive care unit. It should not be forgotten as a cause of ARDS.

Right Atrial Thrombus Presenting as Platypnea-Orthodeoxia Secondary to Reverse Lutembacher Syndrome: A Case Report.

Platypnea-orthodeoxia syndrome (POS) is defined by dyspnea and deoxygenation due to a change in body position from lying down to an upright position. We present a case of a large right atrial (RA) thrombus likely due to a right coronary artery fistula in a patient with a patent foramen ovale (PFO). On imaging, the thrombus was thought to be an atrial myxoma involving the tricuspid valve; however, after surgical excision and histopathological analysis, it was noted to be a cystic thrombus. Red-brown material along with vascular elements was noted on histopathology. Post-surgery, the patient was critically ill and died due to severe tricuspid regurgitation (TR) and hypotension despite using a right ventricle assist device and multiple vasopressors. Reverse Lutembacher syndrome (RLS) is defined as a triad of tricuspid stenosis (TS), elevated RA pressure, and right-to-left atrial shunting. The location of the mass and positional changes could be causing transient RLS from positional TS and interatrial shunting via the PFO causing POS. Cardiac magnetic resonance imaging can help differentiate between intracardiac masses. T1 and T2 signal characteristics and differences in contrast enhancement can help differentiate between a thrombus and a tumor. Treatment options include anticoagulation, thrombolysis, and thrombectomy. If severe TR occurs after surgery, treatment modalities such as caval valves could be an option in the future. Extracorporeal membrane oxygenation to provide right ventricle support in such cases could be considered.

A Unique Case of Community Acquired Proteus mirabilis Meningitis.

Proteus mirabilis, a gram-negative bacterium commonly known for causing urinary tract infections (UTI) can rarely present with central nervous system (CNS) infections. Proteus mirabilis CNS infections are usually encountered in the neonatal and infantile period and occasionally cause brain abscesses. It is an uncommon cause of adult CNS infection. We report the first case of a community-acquired Proteus mirabilis meningitis (PMM) in a patient with Proteus mirabilis UTI, urolithiasis, and bacteremia. Risk factors for gram-negative bacillary meningitis (GNBM) include extremes of age, cancer history, diabetes mellitus, UTI, and nosocomial exposure, with the latter being a more prominent cause of PMM. Compromise of the anatomical defense against CNS infections whether accidental or neurosurgical is another important cause, and approximately two-thirds of reported cases of PMM have occurred after neurosurgical procedures. PMM patients develop fever, altered consciousness, and have an acute clinical course. Antimicrobials that can be used for treatment include third-generation cephalosporins, ciprofloxacin, imipenem/ cilastatin, aztreonam, and intraventricular aminoglycosides. Despite appropriate antibiotic therapy outcomes are poor with severe neurological deficit and death commonly resulting. Nosocomial infections can be drug-resistant and multiple antibiotics should be started while awaiting culture results. Literature review reveals that treatment with intraventricular aminoglycosides when attempted has shown bacteriological cure indicating this can be an important treatment approach. Due to the acute clinical course and high morbidity and mortality, we recommend starting multiple antibiotics with different mechanisms of action as soon as the disease is suspected. Our patient was initially started on ceftriaxone, vancomycin, acyclovir, and ampicillin for UTI and meningoencephalitis. The antibiotics were later consolidated to cefepime based on blood, urine and, cerebrospinal fluid cultures growing pan-sensitive Proteus mirabilis. Her clinical condition continued to worsen and ciprofloxacin was added. However, due to the progressive decline in her condition, the family elected for inpatient hospice care and intraventricular aminoglycosides were not attempted.

A rare case of rectal bleeding and Fusobacterium mortiferum sepsis due to solitary fibrous tumour originating from the mesentery.

Solitary fibrous tumours (SFTs) are rare mesenchymal tumours that are mostly seen in the pleura. Lately, they have also been described in other locations. Recent discovery of the NAB2-STAT6 fusion gene which is specific for SFTs has led to an accurate diagnosis of SFTs. The occurrence of SFTs in the mesentery is very rarely reported in the literature. We report a case of a 63-year-old female who presented with abdominal pain, rectal bleeding and Fusobacterium bacteraemia, who was ultimately found to have a mesenteric SFT.

Association of cigarette smoking with irritable bowel syndrome: A cross-sectional study.

Background: Irritable Bowel Syndrome (IBS) is one of the most commonly diagnosed gastrointestinal disorders, and its etiology is believed to be multifactorial. The role of smoking in the pathophysiology of IBS still remains inconclusive. Hence, we aim to investigate whether or not an association exists between smoking and IBS. Methods: A cross-sectional study was conducted in a tertiary care hospital of Karachi. A sample size of 200 smokers and 200 non smokers was selected. A two-part self-reported questionnaire was administered to the participants and the diagnosis of IBS was based on the Rome III diagnostic criteria. All data were analyzed using the Statistical Package for the Social Sciences version 17. Statistical tests employed were Independent samples t-test, chi-square test, and binary logistic regression analysis to obtain Odds Ratio (OR) for various variables. A P-value <0.05 was considered statistically significant. Results: Overall prevalence of IBS based on Rome III criteria was 9.5% (95% CI 9.45-9.60). Smoking was significantly found to be associated with IBS (P=0.002). Binary logistic regression analysis indicated that non-smokers were more likely to have IBS (Crude OR: 3.00, 95% CI 1.23-7.30) than smokers, and females were more likely to have IBS (Crude OR: 3.73, 95% CI 1.56-7.69) than males. Age, BMI, and food groups were not found to be significantly associated with IBS. Conclusion: Our study concludes that IBS was more prevalent among non-smokers and amongst females. Further studies are required to firmly establish the role of smoking in IBS.

Predictors of Mortality in Patients Undergoing Mitral Valve Replacement.

OBJECTIVE: Although mitral valve replacement is frequently performed in patients of all age groups, there are few studies available which determine the causes of operative mortality in mitral valve replacement especially in our region. Therefore, the objective of this study was to identify factors that are significantly associated with operative mortality in mitral valve replacement. METHODS: From August 2012 to March 2013, 80 consecutive patients undergoing mitral valve replacement in a single tertiary hospital were included. Patients with a history of previous coronary artery bypass graft surgery or congenital heart problems were excluded from the sample. The included patients were observed for a period of 30 days. Pre and post-operative variables were used to identify significant predictors of mortality. RESULTS: The overall hospital mortality (30 days) was 15%. High post-perative creatinine (P =0.05), high ASO titre (P=0.03), young age (P=0.011), low cardiac output (P=0.0001), small mitral valve size (P=0.002) and new onset of atrial fibrillation (P=0.007) were the significant independent predictors of operative morality. CONCLUSION: Mitral valve replacement can be performed in third world countries with limited resources with low mortality. However, optimal selection of mitral valve size can help to improve operative mortality.