Copper Deficiency Myeloneuropathy: An Atypical Presentation of Guillain-Barré Syndrome

Copper (Cu) deficiency myeloneuropathy due to acquired Cu deficiency is both rare and debilitating. More women than men are affected, involving patients aged 32-80 years. Cu itself is a key component of the nervous system, involved in electron transport, oxidative phosphorylation, antioxidant defense, catecholamine synthesis, and iron homeostasis. Afflicted patients usually present with anemia and leukopenia, along with subacute gait disorder with prominent sensory ataxia/spasticity, impaired vibration/position sense, and a positive Romberg sign. Etiologies of Cu deficiency include gastric surgery, zinc overconsumption, dietary deficiency, Celiac disease, Wilson\u27s disease, cystic fibrosis, and IBS. We present the case of a 63 y.o. woman with past medical history of limited stage small cell lung cancer in complete remission for 6 months, COPD, hypertension, supraventricular tachycardia status post ablation who presented with a 2-month history of shortness of breath and weakness, numbness and paresthesias of bilateral upper/lower extremities. Patient reported increasing difficulty grasping objects, increasing gait impairment, and 6-8 falls during this period. Initial workup at outside hospital (OSH) included normal findings on MRI Brain, C-spine, T-spine and L-spine. A normal cell count and protein lumbar puncture (LP) ruled out Guillain-Barré Syndrome (GBS). CSF cytology was negative for malignant cells. Paraneoplastic labs including acetylcholine receptor antibody and voltage-gated calcium channel antibody were negative. Given the unknown etiology of the patient’s condition and her hypercoagulable state, Neurology at OSH deemed IVIG inappropriate. After transfer to our hospital, she displayed dysmetria and dysdiadochokinesia, diminished strength bilaterally, and fatigue. EMG showed diffuse primarily demyelinating \u3e axonal polyradiculoneuropathy of the arms and legs concerning for peripheral demyelinating disease. Negative inspiratory force (NIF) was 60 and functional vital capacity (FVC) was 1350, thus mechanical ventilation was not indicated. She underwent plasmapheresis on 08/12/19 with concerns of GBS variant. IVIG was not considered with prior history of cancer. Repeat EMG on 08/23/19 showed worsening of the patient’s neuropathy with greater axon loss and motor unit dropout in proximal lower extremity muscles, with demyelinating features largely unchanged. Neurology recommended vitamin deficiency labs, including vitamins B1, B3, B6, B12, and E, folate, zinc, Cu and heavy metals. Patient had a Cu level of 473, and Neurology recommended lifelong elemental Cu supplements, 6 month pyridoxine supplementation, and avoidance of zinc supplementation, citing 6 weeks’ recovery time. Patient was discharged to a rehabilitation facility where her strength and sensation improved. She followed up with Neurology outpatient for care. We present an atypical case of GBS caused by Cu deficiency. While GBS was high on our differential in this case, it is believed to be autoimmune in origin. Therefore, negative work up for autoimmune disease should prompt investigation into vitamin or mineral deficiencies in a chronically debilitated patient as a potential root cause for neurologic dysfunction. While Cu deficiency is uncommon and requires years to manifest, it is important to consider in patients with ascending motor paralysis, gait issues, and sensory loss. Cu supplementation generally prevents further neurologic deterioration, but improvement of neurologic symptoms is variable and limited to sensory faculties. Most patients experience residual deficits, but hematologic parameters often respond well to therapy and respond completely.https://scholarlycommons.henryford.com/merf2020caserpt/1078/thumbnail.jp

Predicting prognosis in large cohort of decompensated cirrhosis of liver (DCLD)- a machine learning (ML) approach

Background and aims: Onset of decompensation in cirrhosis is associated with poor outcome. The current clinico-biochemical tools have limited accuracy in predicting outcomes reliably. Identifying the predictors with precision model on the big data using artificial intelligence may improve predictability. We aimed to develop a machine learning (ML) based prognostic model for predicting 90 day survival in patients of cirrhosis presenting with decompensation. Method: We analysed electronic medical records retrospectively of hospitalised cirrhosis patients at the ILBS, with a complete 90-day follow-up. Clinical data, laboratory parameters and organ involvement were serially noted. AI-modelling was done after appropriate mining, feature engineering, splitted randomly into train and testsets (20:80). The class imbalance problem was handled by random over-sampling technique, to make balanced 50:50 ratios. After 10- fold cross validation, 3 repetitions and grid search for optimal hyper parameters, the XGB-CV model was chosen. AUC was the primary selection criteria and confusion matrix was used to compare AUCs between AI-models and existing indices; CTP and MELD-score. Results: Total of 6326 patients [mean age 48.2 ± 11.5 years, 84% male, Mean CTP 10.4 ± 2.2 and MELD Na-30.4 ± 11.9, alcohol 49.4%] were included. Ninety day mortality was 29.2%. Acute insult was identified in 80% cases; of which extra-hepatic 49%, hepatic 46% and unknown 5% cases respectively. The XGB-CV model had the best accuracy for prediction of 90 days event in the train set 0.90 (0.90–0.93), validation set 0.80 (0.79–0.81) and for overall dataset 0.80 (0.79– 0.81). The AUC of the XGB-CV model was better than CTP and MELD Na-score by 16% and 15% respectively. The prediction model considered 43 variables; 18 of which predicted the outcome, and 10 maximum contributors are shown in concordance classifier. The most contributors to poor outcome included, index presentation as HE, diagnosis of AD/ACLF/ESLD, PT-INR, serum creatinine, total bilirubin, acute insult etiology, prior decompensation, acute hepatic or extrahepatic insult, leukocyte count and present duration of illness. In the Decision Tree Model, the presence of HE, PT-INR and syndromic diagnosis of AD or ACLF/ESLD was able to stratify the patients into low (22%), intermediate (23–46%) and high risk (\u3e75%) of mortality at 90 days. Conclusion: The AI based current model developed using a large data base of CLD patients presenting with decompensation immensely adds to the current indices of liver disease severity and can stratify patients at admission. Simple ML algorithms using HE and INR besides syndromic presentation, could help treatment decisions and prognostication

Delayed reaction to drugs often faces delayed diagnosis.

Learning Objective #1: Suspect DRESS in setting of SIRS with eosinophilia Learning Objective #2: Multiple medications make the diagnosis of DRESS difficult CASE: The patient is a 60-year-old female with a history of end stage renal disease secondary to hypertension on peritoneal dialysis who presented secondary to acute onset of abdominal pain, swelling, and a maculopapular rash. Of note, she was recently hospitalized with methicillin sensitive staphylococcus aureus peritonitis, for which she was initially treated with vancomycin and cefepime, before antibiotics were de-escalated to cefazolin, for which she completed a 21 day course. Upon arrival, she was febrile and hypotensive(BP 50/30), with evidence of leukocytosis(70% eosinophils), elevated transaminases, and a positive ANA (speckled, titer 1:160). She was initially re-started on cefazolin, while repeat infectious work up was pending. Blood, urine, respiratory and peritoneal cultures, chest X-ray, abdominal ultrasound and fungitell were all negative and antibiotics were held. In addition, testing for HIV, viral hepatitis, RF, complements, dsDNA Ab, ANCA, anti-Smith Ab, and anti-Scl-70 Ab were also negative. Given persistently elevated liver enzymes (AST 178, alkaline phosphatase 652), she underwent liver biopsy, which showed portal inflammation with lymphocytes and minimal portal fibrosis, consistent with drug induced liver injury. Dermatology performed a punch biopsy of a chest wall lesion, which showed subacute spongiotic dermatitis. The patient was diagnosed with a drug reaction with eosinophilia and systemic symptoms (DRESS) in the setting of exposure to multiple recent antibiotics. Her rash, eosinophilia, and transaminitis subsequently improved with systemic corticosteroid therapy. IMPACT: DRESS can be difficult to distinguish from other infections, autoimmune disease, or hypereosinophilic syndrome. Our patient presented with multiple systemic inflammatory response criteria, resulting in an initial suspicion for infection. Finding the culprit drug for DRESS was further confounded by the use of multiple antibiotics.This case highlights the potential hazards of polypharmacy and the importance of de-escalating antibiotics when appropriate. DISCUSSION: DRESS is a rare and potentially life threatening hypersensitivity reaction, characterized by fever, lymphadenopathy, facial edema, maculopapular rash, eosinophilia and involvement of multiple organ systems (most commonly the liver, kidney, and lungs). Antiepileptic agents, sulfa drugs, ampicillin, minocycline, and vancomycin have been reported as causal agents of DRESS. In most patients, the reaction begins within 2-6 weeks after the introduction of the offending medication. The etiology of DRESS in our patient was somewhat unclear, as she was simultaneously exposed to multiple antibiotics, all of which could be implicated as the cause of the syndrome. While skin allergen testing can be helpful in situations where the etiology of DRESS is unclear, this was deferred in our patient due to the severity of disease

Avoiding painful needles: A case report on diagnosing eosinophilic granulomatosis with polyangiitis.

Learning Objective #1: Recognize Eosinophilic Granulomatosis with Polyangiitis as a cause of eosinophilia despite negative anti-neutrophil cyto-plasmic antibodies CASE: A 73 year old male with a past medical history of asthma and chronic left lower extremity pain presented to the Emergency Department with the primary complaint of acute left lower extremity pain and numbness, as well as subacute bilateral lower extremity swelling. Upon further questioning, he did admit to dyspnea on exertion without orthopnea, PND, fever, chills, cough, sputum production, weight loss, or malaise. Initial chest X-ray was concerning for an interstitial process and CT chest showed lower lung ground glass and tree-in-bud opacities, bronchial wall thickening, mucous plugging, and inter-lobular septal thickening. Laboratory work-up was significant for leukocytosis with 70% eosinophilia, total IgE \u3e 3000, erythrocyte sedimentation rate 102, C-reactive protein 1.3, Rheumatoid Factor 300, and negative p and c-Anti-neutrophil cytoplasmic antibodies. Bronchoscopy guided biopsy results were negative for vasculitis in medium sized pulmonary vessels. EMG study showed left leg and foot sensory and motor neuropathy. Skin punch biopsy for a transient petechial rash over the shins showed leukocytoclastic vasculitis rash. Sural nerve biopsy showed extravascular eosinophilia and granulomatous vasculitis, consistent with EGPA. The patient was then discharged home on high dose steroids. IMPACT: EGPA is a rare, but not uncommon, multiorgan disease that should be suspected in patients presenting with asthma, sinusitis and eosinophilia. Although p-ANCA testing is commonly done on initial work up, it is neither sensitive nor specific. Special attention should be paid to ANCA negative patients presenting with mononeuritis multiplex, as nerve biopsy can confirm the diagnosis. This will avoid other invasive procedures, such as surgical lung biopsy. DISCUSSION: Characteristic laboratory tests to diagnose EGPA include eosinophilia, elevated IgE and p-ANCA positivity. However, ANCA is not considered specific toEGPA as it is positive in only 30 to 60 percent of patients with definite vasculitis. As discussed in the case above, when there is a high clinical suspicion of EGPA, biopsy should be pursued to confirm the presence of vasculitis. Although surgical lung biopsy is the gold standard, if skin or nerve involvement is present, pursuing biopsies of a less invasive site is preferred. In terms of extrapulmonary organ involvement, nerve involvement has the highest prevalence (78%), followed by joint and muscle (57% each), and skin and kidney (48% each). In one case series, 71% of patients with EGPA associated neuropathy developed mononeuritis multiplex, presenting as sensory impairments of the extremities. The most common distribution of nerve involvement was the common peroneal nerve, followed by sural nerve. On sural nerve biopsy, eosinophilic infiltrates were seen on 7 out of 15 cases, which is considered to be the hallmark of EGPA

To Clot or to Bleed: Thrombosis as a First Sign of Microscopic Polyangiitis

Learning Objective #1: Recognize ANCA-associated vasculitis in a patient with thrombosis Learning Objective #2: Management of diffuse alveolar hemorrhage in the setting of acute thrombosis CASE: A 59-year-old female with a history of stroke with residual right-sided weakness presented with dyspnea and lower extremity swelling. She was febrile, tachycardic, and required supplemental oxygen (O2). Laboratory studies showed an acute kidney injury (AKI). Lower extremity dopplers revealed bilateral deep vein thrombosis (DVT), and she was started on heparin for DVT and presumed pulmonary embolism (PE). Computed tomography (CT) PE was not performed due to AKI. Chest xray showed bilateral airspace opacities, so antibiotics were started. The patient clinically worsened and developed hemoptysis with increasing O2 requirements. CT chest showed concern for alveolar hemorrhage. Anticoagulation was stopped and the patient was intubated. Bronchoscopy confirmed diffuse alveolar hemorrhage. Rheumatologic workup showed ESR 111, ANA 1: 320 (speckled), and positive MPO (p-ANCA) of 115. Left kidney biopsy revealed focal segmental necrotizing and crescentic glomerulonephritis consistent with ANCA-associated pauci-immune glomerulonephritis, microscopic polyangi-itis (MPA). Plasmapheresis and hemodialysis was started due to worsening kidney function. She clinically improved, was extubated, and eventually weaned off oxygen. Induction with Cyclophosphamide and high-dose steroids was begun. Her AKI resolved, no longer requiring dialysis. After a risk-benefit discussion, warfarin was started, and the patient returned home. She was transitioned to maintenance therapy on Azathioprine and remained clinically stable at her three year follow up. IMPACT/DISCUSSION: We present a case of thrombosis as a first sign of severe microscopic polyangiitis. The most common clinical symptoms of MPA include fatigue, cough, dyspnea, and arthralgias. Although it is a pulmonary-renal syndrome, renal insufficiency is only present in 18% of patients on presentation. In our patient, a DVT (originally thought to be due to immobilization from stroke) was the first sign of extensive MPA. The accompanying respiratory symptoms were presumed to be due to PE, and therefore a CT scan was not initially performed. The etiology of the hyper-coagulable state in such patients is unclear, but circulating antiplasminogen antibodies have been demonstrated in those who develop clots. This case was further complicated by diffuse alveolar hemorrhage, a rare but life-threatening complication of MPA. Immunosuppressive therapy is required in almost all patients with active disease. Conclusion: Patients with ANCA-associated vasculitis have a high risk of thrombosis, but it is rarely the presenting sign. Suspicion in patients with concomitant renal insufficiency and pulmonary symptoms can lead to early diagnosis. Despite being hypercoagulable, anticoagulation may not be the appropriate initial treatment as pulmonary hemorrhage can worsen outcomes

Analysis of Visit Factors Associated with Colorectal Cancer Screening in an Academic Outpatient Care Center

Background: Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the second leading cause of cancer related death in the United States. CRC screening recommendations by all major organizations allow for either the use of stool-based tests such as fecal immunochem-ical test (FIT), fecal occult blood testing (FOBT) and multitargeted stool DNA (such as Cologuard) or visual tests such as Colonoscopy, CT Colonography, and flexible sigmoidoscopy. Prior literature has shown that screening services are inconsistently delivered across practice settings and continue to be underutilized. Most insurance cover preventative visits to accomplish screening goals and offer services in form of outreach, however, data is lacking on effectiveness of these visits. Likewise, interventions to increase CRC screening uptake have focused on modifying provider attitudes, although, studies have not addressed provider level and gender as a potential factor. Our primary objective was to assess the frequency and type of CRC screening offered by primary care doctors. Our secondary objective was to assess how type of visit and provider factors affect if screening was offered and the type of screening offered. Methods: A retrospective chart review of 2196 patients who were seen in an outpatient academic tertiary care center was performed. Patients between the ages 50-75 years old who had a primary care doctor and were seen in clinic between July 1, 2017 and July 31, 2018 were assessed. Screening offered was defined as either stool tests (FIT, FOBT and Cologuard) or visual tests (Colonoscopy and CT colonography). Results: A total of 2196 patients met our criteria. The mean age was 62.7 years; body mass index (BMI), 31.1kg/m2; females, 54.7%. Cohort was divided into Group A (62%), comprising of people who did not have CRC screening ordered and Group B (38%), who had one or more CRC screening tests ordered. In Group B, some patients had more than one test ordered: 83.1% had Colonoscopy ordered, 10.7% had Cologuard ordered, 13.5% had FIT/FOBT ordered. The rate of colonoscopy completion was 14.7%, and stool testing completion was 34-37.5%. Out of 739 visits during which CRC screening was implemented, 90% were office visits. Surprisingly, having a preventative visit was not associated with an increased likelihood of having CRC screening test ordered (p=0.91). Among patients who had either test ordered, 65.6% of Colonoscopies or 48.4% of Stool tests were ordered by residents (p\u3c 0.001). Conclusions: A significant amount of patients (62.3%) that were seen by their primary care doctor had no CRC screening ordered. Having a wellness visit was not associated with having CRC screening tests ordered. Although colonoscopy was the most commonly ordered screening test, compliance to stool testing was twice as that of colonoscopy. Residents as provider were more likely to order colonoscopy compared to senior staff

Delayed reaction to drugs often faces delayed diagnosis.

Learning Objective #1: Suspect DRESS in setting of SIRS with eosinophilia Learning Objective #2: Multiple medications make the diagnosis of DRESS difficult CASE: The patient is a 60-year-old female with a history of end stage renal disease secondary to hypertension on peritoneal dialysis who presented secondary to acute onset of abdominal pain, swelling, and a maculopapular rash. Of note, she was recently hospitalized with methicillin sensitive staphylococcus aureus peritonitis, for which she was initially treated with vancomycin and cefepime, before antibiotics were de-escalated to cefazolin, for which she completed a 21 day course. Upon arrival, she was febrile and hypotensive(BP 50/30), with evidence of leukocytosis(70% eosinophils), elevated transaminases, and a positive ANA (speckled, titer 1:160). She was initially re-started on cefazolin, while repeat infectious work up was pending. Blood, urine, respiratory and peritoneal cultures, chest X-ray, abdominal ultrasound and fungitell were all negative and antibiotics were held. In addition, testing for HIV, viral hepatitis, RF, complements, dsDNA Ab, ANCA, anti-Smith Ab, and anti-Scl-70 Ab were also negative. Given persistently elevated liver enzymes (AST 178, alkaline phosphatase 652), she underwent liver biopsy, which showed portal inflammation with lymphocytes and minimal portal fibrosis, consistent with drug induced liver injury. Dermatology performed a punch biopsy of a chest wall lesion, which showed subacute spongiotic dermatitis. The patient was diagnosed with a drug reaction with eosinophilia and systemic symptoms (DRESS) in the setting of exposure to multiple recent antibiotics. Her rash, eosinophilia, and transaminitis subsequently improved with systemic corticosteroid therapy. IMPACT: DRESS can be difficult to distinguish from other infections, autoimmune disease, or hypereosinophilic syndrome. Our patient presented with multiple systemic inflammatory response criteria, resulting in an initial suspicion for infection. Finding the culprit drug for DRESS was further confounded by the use of multiple antibiotics.This case highlights the potential hazards of polypharmacy and the importance of de-escalating antibiotics when appropriate. DISCUSSION: DRESS is a rare and potentially life threatening hypersensitivity reaction, characterized by fever, lymphadenopathy, facial edema, maculopapular rash, eosinophilia and involvement of multiple organ systems (most commonly the liver, kidney, and lungs). Antiepileptic agents, sulfa drugs, ampicillin, minocycline, and vancomycin have been reported as causal agents of DRESS. In most patients, the reaction begins within 2-6 weeks after the introduction of the offending medication. The etiology of DRESS in our patient was somewhat unclear, as she was simultaneously exposed to multiple antibiotics, all of which could be implicated as the cause of the syndrome. While skin allergen testing can be helpful in situations where the etiology of DRESS is unclear, this was deferred in our patient due to the severity of disease