No abstract

Introduction MMF is an immunosuppressive drug frequently used for graft-versus-host disease (GVHD) prophylaxis and management. MMF-induced colitis is a known complication, however, details regarding its clinical manifestations, treatment options, and outcomes are less clear. Differentiating MMF-induced colitis from gut GVHD on the basis of histology may be difficult, hence deeper clinical understanding of MMF-induced colitis can be valuable. The aim of this systematic review was to analyze the reported cases of MMF-induced colitis to provide summative data. Methods Inclusion criteria included prospective or retrospective clinical studies and case series, reported in English language, providing data on clinical manifestations, treatment options, and outcomes of colitis induced by MMF or its derivatives (such as mycophenolic acid, and enteric coated mycophenolate sodium). Cases were included irrespective of the indication of MMF. Using various search terms, all cases indexed in PubMed, EMBASE, Cochrane and Scopus from inception to July 2016 were reviewed. The bibliography of each relevant article was searched for additional reports. Non-human studies and colitis attributed to other etiologies such as infection, GVHD or inflammatory bowel disease were among the 138 articles that were excluded. Results Forty-four articles with a total of 544 patients and 560 episodes of suspected or confirmed MMF-induced colitis were included. The median age was 41 years (range 5-70), and 30% were females. The latency between the use of MMF and onset of colitis was 990 days (range 3- 5760). Watery diarrhea as frequent as every 20 minutes in one case and large volume at times, was the presenting symptom in 92% of cases. Other less common presentations included bloody diarrhea, abdominal pain, and steatorrhea. MMF was discontinued or dose reduced in 65%, switched to enteric coated mycophenolate mofetil sodium in 14% and continued in 21% of cases. Ninety-eight percent of cases managed with discontinuation or dose reduction of MMF responded to the treatment. About 93% of cases who switched from MMF to enteric coated mycophenolate mofetil sodium responded. Among the patients who continued MMF, diarrhea was persistent in 17% while it resolved spontaneously in 83% (Figure 1). The median time to response to either change to enteric coated mycophenolate sodium or discontinuation of treatment was 20 days (range 1-45). Complications developed in 3.5% (n=19) of cases including graft rejection in solid-organ transplant (n=11) after discontinuation or dose reduction of MMF, acute dehydration (n=6), toxic colitis (n=1), and severe weight loss of >60 pounds (n=1). Conclusion MMF-induced colitis generally presents with watery diarrhea but rarely blood may be noted in stool. The latency period can be as long as months to years, hence a long latency period does not exclude the possibility. A vast majority of patients respond to cessation of MMF or dose reduction within a few weeks, however, cessation of MMF may result in graft rejection. In cases where continuation of immunosuppressive therapy is considered important to prevent graft rejection, alternate management option for management of MMF-induced colitis could include switching to a different drug formulation. Figure 1 Management and outcomes of MMF-induced colitis Figure 1. Management and outcomes of MMF-induced colitis Disclosures No relevant conflicts of interest to declare.

A 71-year-old female with history of right lower lobe (RLL) lesion (noted six years ago on chest x-ray [CXR]) and 45-pack year smoker presented to the Emergency Room for shortness of breath (SOB). She reported two months of worsening SOB, productive cough, and unintentional weight loss. Physical exam revealed RLL wheezes. Her oxygen saturation was 89% on room air. Admission labs showed leukocytosis and elevated procalcitonin (Table 1). Initial imaging demonstrated a large RLL multiloculated lung abscess (LA) (Figure 1). We initiated oxygen and intravenous (IV) broad spectrum antibiotics. Coronavirus 2019 (COVID-19) came back positive and hydroxychloroquine was started. Thoracentesis of the LA revealed Streptococcus (Strep) anginosus that was susceptible to penicillins. The patient was then switched to Amoxicillin for 4 weeks. Repeat Computed Tomography (CT) of chest after 4 weeks revealed RLL consolidation evolution with decreased parenchymal fluid loculations (Figure 2). The pulmonologist restarted Amoxicillin for 4 weeks, ordered repeat COVID-19 testing, and referred to oncology.

Mad honey, which is different from normal commercial honey, is contaminated with grayanotoxins and causes intoxication. It is used as an alternative therapy for hypertension, peptic ulcer disease and is also being used more commonly for its aphrodisiac effects. Grayanotoxins, found in rhododendron plant, act on sodium ion channels and place them in partially open state. They also act on muscarinic receptors. Cardiac manifestations of mad honey poisoning include hypotension and rhythm disorders such as bradycardia, nodal rhythm, atrial fibrillation, complete atrioventricular block or even complete heart block. Additionally, patients may develop dizziness, nausea and vomiting, weakness, sweating, blurred vision, diplopia and impaired consciousness. Diagnosis is made with history of honey intake and clinical presentation. Treatment is symptomatic. Patients presenting with severe hypotension and bradycardia may need prompt treatment with fluids, atropine or even temporary pacing if other measures fail. Although fatalities are rare, poisoning may be hard to recognize and arrhythmias may be life-threatening.