Resident Poster Competition

NM Scientific Chapter Meeting November 6, 7, 8, 2014 Residents’ Committee Alisha Parada, MD Patrick Rendon, MD Co-Chairs

Lida Fatemi, MD Category: Clinical Vignette

An Usual Infection of a Peculiar Site

HPI: A 61 year old male smoker presented to the emergency department with progressive worsening swelling of the left mandible for the past 12 months. He decided to come to the ED when he noted water draining from an area on his left jaw when he drank fluids. PMH: The patient had a 30 pack year history. PE: Vital signs were normal. He had a swollen left jaw with a fistula on the left sub-mandibular area that had exudative drainage. Patient was missing all his teeth and had left lower gingival swelling. There were no ulcers or other lesions noted in the mouth. The remainder of the PE was unremarkable. Labs: Normal WBC. A CT of the head showed osteomyelitis of the left jaw. Hospital Course: Biopsy of the jaw bone was taken by ENT. ID consultants recommend empiric IV antibiotics that were started immediately. Two weeks after the jaw biopsy, cultures grew actinomyces. The patient was then started on IV Nafcillin for 6 weeks. At week 4 ENT readmitted the patient to perform a segmental mandibulectomy and fibular free flap reconstruction. During the surgery, a few submandibular lymph nodes were removed and sent for pathology and patient is currently under worked up by Heme/Onc consultants for possible SLL vs CLL. He finished the 6 week course of IV Nafcillin and was then started on oral Amoxicillin 500 mg TID planned for a 12 months course. Physical exam during follow up with his PCP 12 weeks after jaw reconstruction showed well healed jaw surgical sites with some healing difficulty of the fibular free flap. His facial form had returned to normal with minimal loss of sensation. This case illustrates an unusual cause of osteonecrosis of the jaw due to actinomyces infection. Treatment of actinomyces requires a long period of antibiotic administration usually by IV and oral routes in addition to surgical removal of infected tissue. Additonally, cultures of the organism may take up 14 to 21 days for growth. In fact, actinomyces infection of the jaw is more common in animals than in humans. Actinomyces is a gram positive facultative anaerobe commonly found in the oral flora and more commonly seen pathologically in immune— compromised hosts. In this patient given the pathologic abnormalities that noted in his submandibular lymph nodes this could be contributed to SLL vs CLL which is currently under work up by Heme/Onc consultants. Christine Johnson, MD Category: Clinical Vignette

Topiramate-Induced Renal Loss Causing Severe

A 52 year-old female presented with complaint of weakness and tremors, as well as severe hypokalemia (1.8 mmol/L) just two months after taking topiramate for multiple pain symptoms and anxiety. Patient was also taking hydrochlorothiazide for blood pressure control for a number of years with no evidence of hypokalemia on labs prior to this. On admission, the patient’s HCTZ was held and potassium was initially repleted with intravenous and oral potassium totaling 280 mEQ. Two days after holding HCTZ, the potassium continued to be low, therefore, the transtubular potassium gradient (TTKG) was calculated as 11.6 with a urine osmolality of 477, serum osmolality of 300, urine potassium of 33.2, and initial serum potassium of 1.8. In the setting of TTKG >7, renal potassium loss had to be considered as a cause of this patient’s hypokalemia. Topiramate was stopped as this has been shown in two case reports to be associated with (RTA) and refractory hypokalemia. The patient was normotensive and hyperaldosteronism was not present. She was slightly alkalotic with a pH of 7.46 on ABG. The patient’s serum potassium returned to normal after 3 days of rigorous oral and intravenous repletion. The patient followed up in three days, one week and two weeks after hospitalization for rechecks of potassium, which were found to be normal. Topiramate has carbonic anhydrase inhibitor activity and is associated with nephrolithiasis, RTA and osteoporosis as it impairs both the normal reabsorption of filtered HCO3− by the proximal renal tubules and the excretion of H+ by the distal renal tubules. Bicarbonate loss into the urine increases the negativity of the lumen, thereby increasing potassium secretion into the lumen, resulting in hypokalemia. Physicians should consider monitoring patient’s serum K and HCO3- after initiating topiramate for migraine prophylaxis, epilepsy, bipolar disorder, or PTSD. The half-life of topiramate is between 19-23 hours. A baseline metabolic panel is recommended upon starting topiramate, and the time frame for re-checking electrolytes is two to three weeks. If the serum bicarbonate concentration is <17 meq/L or if a >5-meq/L decrease from baseline occurs, it would be prudent to consider decreasing the dose or discontinuing topiramate. Uzair Ghori, MD Category: Clinical Vignette

Endobronchial Ultrasound: Novel approach in diagnosing thymic carcinoma

Introduction: Anterior thymoma/thymic carcinoma is epithelial in origin. It is classified as anterior mediastinal tumor and diagnosis of thymic carcinoma with FNA in situation where mediastinscopy cannot be performed is difficult to establish .FNA biopsy under USG guidance of such mass can establish histological diagnosis of thymoma with histochemical confirmation.

Case presentation: A 55-year-old male presented to the ER with a 4-6 month history of weight loss and dyspnea. He also endorsed anorexia (12 months), fatigue (12 months), hoarseness in voice, retrosternal chest pain/pressure and dry cough for 4-6 months. He denies joint pain or skin rash. Past medical history was significant for 45 pack years of smoking (quit 1 year ago), drinking, cocaine and marijuana use but quit 1 year ago. His occupation included welding and working in a liquor store. There is remote history of travelling to cuba and he has cats/chickens as pets. Patient was hemodynamically stable with saturation of 95% on 1 liter of oxygen while physical examination revealed decreased breath sounds over right lung base. Labs showed Creatinine 1.10, total bilirubin 1.5 and direct bilirubin 1.2. Hepatitis and HIV panel were negative. High resolution computed tomography of chest showed an anterior mediastinal mass which was compressing the pulmonary artery. Thoracocentesis was unremarkable for malignant cells on cytology. Samples of the lesion were obtained utilizing endobronchial ultrasound with FNA which were subsequently stained with H & E, Papanicolou and CD5 stain.

Discussion: Thymic carcinoma is rare with incidence of 0.06% of all thymic tumors with 5 year survival rate between 30-50%. Common approaches to diagnosis include utilizing image-guided FNA or mediastinoscopy for obtaining histological samples. Use of FNA can be limited since thymomas at time contain the thymic carcinoma which can be missed during sampling. The diagnostic yield of FNA is variable and dependent on the expertise of the team which includes pulmonologist plus the pathologist which presents as a challenging task. Mediastinoscopy results in better sample size and diagnostic yield as compared to FNA but is is invasive and associated with greater morbidity. Histochemical stains including CD5 are used for confirming diagnosis.

Conclusion: After histological diagnosis of thymic carcinoma was made, our patient got standard chemotherapy resulting in marked improvement of symptoms and shrinkage of tumor size. References: 1: Greene MA, Malias MA. Aggressive multimodality treatment of invasive thymic carcinoma. J Thorac Cardiovasc Surg. 2003 Feb;125(2):434-6. PubMed PMID: 12579125. 2: Zakowski MF, Huang J, Bramlage MP. The role of fine needle aspiration cytology in the diagnosis and management of thymic neoplasia. J Thorac Oncol. 2010 Oct;5(10 Suppl 4):S281-5. PubMed PMID: 20859120. Prajit Arora, MD Category: Clinical Vignette

A Case Of BK Nephropathy in Native Kidneys Post Lung Transplantation

A 70 year old male patient with history of Usual Interstitial Pneumonitis with unilateral left sided lung transplant done in 2012. Patient was on chronic immunosuppressive regimen of tacrolimus, mycophenolic acid and prednisone. Patient’s baseline creatinine level was 1-1.1. Patient was in his usual state of health when he was noticed to have gradual creatinine elevation to 1.8 in May 2014 and up to 3 in July,2014 with estimated glomerular filtration rate 21. Patient’s tacrolimus level were mostly between 5-8, urine total protein/creatinine ratio of 0.3, urine microscopy was essentially bland at first and subsequently did show presence of decoy cells. Ultrasound kidneys was unremarkable. CMV status was negative, however serum BK virus was at 10 million copies/ml initially. Native renal Biopsy was done which showed active polyomavirus nephropathy, with visible viral inclusions, positive staining for SV-40 large T antigen, and associated tubular cell injury/necrosis and mainly mononuclear tubulitis. There was moderately severe interstitital fibrosis and tubular atrophy (about 40-45% that was out of proportion to the degree of global (13%), and this was likely felt to be due to the polyomavirus nephropathy. Immunofluorescence was unremarkable. Patient’s mycophenolic acid was discontinued secondary to both the BK viropathy as well as leucopenia with continuation of his tacrolimus and prednisone. A course of leflunomide has been started at 10 mg once a day as well as Intravenous Immunoglobulin at 1gm /kg to be given monthly for three months. At present time, approximately two months after initiation of treatment, patient’s serum BK virus is down to 3.5 million copies, however creatinine has remained relatively stable at 2.6 with gfr of 24.

BK nephropathy is an important cause of allograft dysfunction in renal transplant patients. In non-renal solid organ transplant and bone marrow transplant patients, renal dysfunction can occur and is often attributed to calcineurin inhibitor toxicity. However, a review of the literature suggests that BK nephropathy of the native kidneys is becoming an emerging problem in non- renal transplant patients. Christopher Bailey, MD Category: Clinical Vignette

Eyes Wide Shut: An Uncommon Presentation of Recurrent Granulomatosis with Polyangiitis

Introduction: Granulomatosis with polyangiitis (GPA), also known as Wegener’s granulomatosis, is a rare disease characterized by a systemic necrotizing small-vessel vasculitis of unknown origin. It typically affects the upper respiratory tract, lungs, and kidneys, but any organ can be affected. This case presents a particularly unusual presentation of GPA. Case

Description: The patient was a 22-year-old Caucasian female with ANCA-positive GPA. She complained of progressive fever, chills, muscle aches, nausea, vomiting, and severe headache for two weeks. Additionally, she had severe eye pain for one month along with blurry vision and double vision for two months. Her fiancée had noted drooping eyelids and bulging of her eyes, and that she required assistance with most activities of daily living, for one month. Vital signs were normal. Physical exam was notable for bilateral proptosis, severe upper lid ptosis, dilated and fixed pupils, right-sided trochlear palsy, partial right and complete left of the abducens nerve, and altered mental status. Her visual acuity was significantly reduced. Laboratory studies were notable for elevated ESR and CRP. LH, TSH, FT4, FT3 and total T3 were diminished. Lactate and ANCA levels were normal. A head CT scan showed a large suprasellar mass, and an MRI of the head showed leptomeningeal involvement and mild communicating hydrocephalus. On hospital day two, she developed anisocoria and was transferred to the neurosurgery intensive care unit. She also had hypernatremia secondary to . She began cyclophosphamide and steroid therapy. During her 31-day hospital course, she showed dramatic improvement in her vision and extraocular movement. With clinical improvement and regression of the mass, the neurosurgery team decided not to perform a biopsy. There was no evidence of recurrence at a follow-up appointment four weeks later.

Discussion: GPA is a rare disease that can affect all organ systems, leading to significant variation in presentation. This patient showed a classic clinical presentation of granulomatous hypophysitis, displaying hypopituitarism, diabetes insipidus, and visual disturbances. This is very rare, with an incidence of one case per 10 million per year. Based on the patient’s chronic underlying diagnosis, negative infectious workup, and successful response to steroid therapy, granulomatous hypophysitis secondary to GPA remains the most likely diagnosis without the tissue biopsy necessary for a definitive diagnosis. Current medical management for this condition is cyclophosphamide and steroid therapy, which is associated with a 50% decreased chance of relapse as opposed to steroid therapy alone. This patient underwent this therapy with good initial outcome and avoided surgical intervention. This case represents a unique manifestation of GPA known as granulomatous hypophysitis. Prompt medical management is important for favorable clinical outcomes. The dramatic improvement in clinical symptoms and follow-up imaging, along with no evidence of recurrence on follow-up, justify our management. Annashia Shera, MD Category: Clinical Vignette

Sepsis with Transaminitis: Not Always Ischemic Hepatitis

According to the CDC, candidemia is the fourth most common blood stream infection and is strongly associated with immunocompromised hosts; however solid organ infections are rare and normally occur in immunosuppressed transplant patients. A recent French study reported a 3% incidence of hepato-splenic candidiasis in hematological malignancies. We present a rare case of Candida Utilis liver lesions.

A 57-year-old female was admitted to the hematology service with acute promyelocytic leukemia complicated by DIC. A PICC line was placed for access and induction chemotherapy with Idarubicin, arsenic trioxide, and all trans-retinoic acid. Providers initiated prophylactic treatment with Posaconazole, Acylovir and Augmentin. She then received maintenance chemotherapy with Arsenic trioxide and Retinoic acid. On hospital day 12, she became tachycardic and febrile to 40º C. Cefepime and vancomycin were initiated. AST and ALT increased to 405, and 262 respectively. A liver ultrasound demonstrated multiple lesions and an MRI delineated 5.1 cm and 4.6 cm rim-enhancing lesions in different liver lobes. Interventional radiology biopsied the liver and tissue was sent for cultures and zygomycetes PCR. Amphotericin B was then added to increase fungal coverage. Microscopy revealed fungal forms with broad hyphae with wide angled branching and rare septae suggestive of Mucormycosis. Antibiotics and chemotherapy were discontinued and treatment with Amphotericin B and mycafungin continued. In the interim the blood cultures remained negative however DNA PCR confirmed Candida Utilis. Despite treatment, liver lesions continued to grow and she developed fistulas communicating with the abdominal wall. Surgical resection was performed. She continues treatment with oral posocanazole and repeat CT scans reveal no new liver lesions.

Fungal infections occur in hematological patients due to many factors, such as immunosuppressive therapeutic regimens, long-term catheterization, broad-spectrum antibiotic use, and longer survival of immunologically compromised individuals. To our knowledge there have been only 5 cases of candida Utilis reported . In all reviewed case reports, patients with C. Utilis fungemia had central venous catheters. We suspect the possible source of infection was the patients PICC line and interestingly prophylactic antibiotics did not prevent the infection. In conclusion, patients with hematologic malignancies who develop sepsis should have fungemia considered in the differential diagnosis. Non-albicans Candida (NAC) species occur more frequently in this population--a review article by Krcmery et al cited a 40-70% incidence. Most NAC are innately resistant to azole therapy and Fluconazole resistant species of Candida are significantly more common in patients exposed to at least 7 days of antifungal prophylaxis. This presents a challenge for management and prophylaxis against these emerging pathogens in immunocompromised patients. In order to diagnose these infections, physicians should consider sending PCR because these organisms are difficult to culture. Taylor Goot, MD Category: Clinical Vignette

CONNed out of a Diagnosis: A Case of an Ectopic ACTH-Secreting Tumor

Ectopic ACTH-secreting tumors represent a rare clinical entity which can cause a secondary Cushing’s syndrome. These hormone-secreting tumors can result in a syndrome that shares many clinical features of primary hyperaldosteronism (Conn’s syndrome), and typically require a high degree of clinical suspicion for diagnosis.

A 72-year-old female with a past medical history significant for hypertension, non-insulin dependent diabetes mellitus, and tobacco use was referred to the University of New Mexico Hospital from her rural primary care provider for severe refractory hypokalemia. The patient was asymptomatic other than mild lower extremity edema that had been present for the past week and constipation over the last 2.5 weeks. The patient had been treated during this time with increasing doses of laxatives and oral potassium. Failing this treatment with an outpatient potassium level of 2.8 mmol/L and continued constipation, the patient was referred for inpatient evaluation. Upon presentation, the patient’s labs included a potassium of 2.8mmol/L and bicarbonate of 31mg/dL, as well as hyperglycemia, leukocytosis and evidence of a urinary tract infection. Blood pressures ranged from 160-186/79-83mmHg. Initial physical exam was notable only for lower extremity edema. Initial treatment was focused on aggressive potassium replacement and treatment of the patient’s infection. Due to the persistent hypertension and hypokalemia, renin and levels were obtained which were 0.1ng/dL and 7.9ng/dL respectively, not suggestive of hyperaldosteronism. Follow up physical exam found a palpable abdominal mass prompting an abdominal CT scan, which showed colonic thickening and innumerable liver masses. Colonoscopy was grossly normal. Further history obtained suggested that the in-hospital hyperglycemia and hypertension were inconsistent with the patient’s recent outpatient history. 24-hour urine cortisol was obtained which was markedly elevated. An overnight dexamethasone suppression test was performed, with pre-suppression ACTH levels of 460pg/mL and post-suppression levels of 441pg/mL. A liver biopsy showed pathology consistent with small cell carcinoma which further raised suspicion for a paraneoplastic syndrome. The patient was diagnosed with Cushing''s syndrome caused by ectopic ACTH secretion and hyperaldosteronism-like hypokalemia with hypertension and alkalosis. A chest CT would later reveal the primary lung tumor. The patient unfortunately succumbed to her disease soon after diagnosis.

We present a case of an ACTH-secreting pulmonary tumor with a secondary Cushing’s syndrome and hyperaldosteronism-like state. Being that the patient’s chief complaint was constipation, diagnosis was delayed until we achieved a full clinical picture. Our case represents the need for a high index of suspicion and global consideration of a patient’s signs and symptoms, as well as a presentation of a rare entity with a common chief complaint. Jacklyn Nemunaitis, MD Category: Clinical Vignette

A Killer in Disguise: The Mask of Orbital Cellulitis

Orbital cellulitis is a common clinical entity seen by primary care providers in their daily practice. We present a case of a patient with recurrent orbital cellulitis who was ultimately diagnosed with Natural Killer/T-cell lymphoma. Only 8% of lymphomas initially present in the orbital region.

We report a case of a 59-year old male without significant past medical history who was referred to our institution for evaluation of recurrent left orbital cellulitis. The patient reported that in the past 6 months he had experienced 4 episodes of left eye swelling and discharge for which he was prescribed antibiotics resulting in temporary resolution of symptoms. At this presentation the patient had failed to respond to antibiotics and continued to experience high fevers with progressively increasing inflammation. On physical exam, the patient was noted to have marked left orbital edema associated with chemosis of the conjunctiva and proptosis of the left eye. Laboratory evaluation demonstrated pancytopenia with a normal differential. CT revealed increased soft tissue density on the medial and inferior-medial aspect of left orbit associated with pan-sinusitis. No masses or invasion were seen. After a failed response to broad spectrum antibiotics other diagnostic possibilities were considered including granulomatosis with polyangiatis, malignancy and fungal etiologies. ENT performed debridement of the sinuses which confirmed a diagnosis of extranodal NK/T cell lymphoma.

The clinical features of extranodal NK/T cell lymphoma can closely mimic those of other disease entities, and an early diagnosis can present a challenge to the clinician. The clinical course of the disease is aggressive with five-year survival rates ranging from 38 to 45 percent. An aggressive disease of this nature requires clinicians to maintain a high degree of suspicion from the outset to exclude a neoplastic pathology. Christopher Bunn, MD Category: Research

Improving Documentation of Supplements During Medication Reconciliation

Introduction: Research indicates that 15 -20% of Americans have taken some form of supplement in the last 12 months. One study demonstrated over half of patients taking supplements don’t disclose because providers don’t specifically ask. Joint Commission requires documentation of supplements during medication reconciliation but the current EMR formulary does not contain a complete registry of common over-the-counter (OTC) supplements. Supplements must be tediously entered manually as miscellaneous medications. The lack of auto-populating makes documenting patient’s supplement use prohibitively difficult. This lack of medical documentation could result in adverse drug-supplement interactions. Our objective is to improve the documentation of supplements during electronic medication reconciliation.

Process Mapping: The current system for documenting supplements fails in multiple ways, but three main pathways were identified for intervention. The areas for improvement included changing the electronic medication reconciliation process by creating an auto-populating folder of supplements. Educating providers about the importance of supplement documentation and instructing providers to directly ask patients about supplement use.

Interventions: A computerized folder entitled “Supplements” was created in the EMR. This folder contains evidence based dosing of 65 supplements, 32 Chinese herbal preparations and 5 OTC proprietary herbal blends. The folder appears whenever the add medication tab is activated. When a supplement is selected from the folder, a dose, route, and frequency are automatically reconciled into the patient’s medication list. Fifty providers were polled regarding their attitudes toward supplements. 20% indicated that they did not perform supplement reconciliation and 68% indicated that supplement reconciliation was somewhat difficult with the current system. 23% responded that they were least concerned about patient safety and supplement use. Providers were educated about JCAHO requirements for supplement reconciliation and the possible dangers of common supplement-medication interactions. Providers were trained on how to use and document supplements with the new folder. In order to prompt patients to disclose supplement use providers were instructed to ask patients “In addition to your prescribed medications, do you use any supplements, vitamins, minerals, herbs, nutritional supplements or over the counter medications?”

Measuring the Outcome: 27 supplements were documented as patient medications in the EMR the month before the interventions. Thirty one days after the interventions, 41 documented supplements appeared in patient’s medication lists. This represents a 51% increase in supplement documentation Conclusion: Using a dedicated supplement folder that automatically populates dose, route, frequency and indication improves the documentation of OTC supplements in an outpatient primary care clinic. Elyce Sheehan, MD Category: Clinical Vignette

A Heart Full of MRSA

Patients with hepatic cirrhosis commonly have complications such as ascites, edema, and hydrothorax. Although relatively rare, pericardial effusions in patients with cirrhosis have also been documented. Infectious pericarditis as a cause of pericardial fluid collection is more common. Infections are common among patients with cirrhosis; the most frequent infections are healthcare-acquired. Methicillin resistant staph aureus (MRSA) is one such infection often associated with severe, invasive diseases like soft tissue infection, bloodstream infections, and pneumonia. There is significant literature on MRSA causing purulent pericarditis. Pericardial tamponade can be life-threatening thus a high index of suspicion must be maintained to ensure rapid detection and initiation of treatment.

A 43-year-old female with history of alcoholic cirrhosis and intravenous drug abuse was admitted to the MICU for septic shock and upper GI bleeding. Initial cultures indicated urine infection with escherichia coli as the likely source of sepsis which was treated with ciprofloxacin; her GI bleed was treated with octreotide and pantoprazole. The patient initially recovered and was transferred to the floor where she developed aspiration pneumonia, which was treated with intravenous antibiotics. She subsequently developed significant edema and leukocytosis thought secondary to initiation of corticosteroids for alcoholic hepatitis. After nearly two weeks on the floor, she developed sudden onset, extreme abdominal pain, left lower extremity pain, and hemodynamic instability. She was transferred back to the MICU, where she required broad spectrum antibiotics, blood pressure support and intubation for hypoxic respiratory failure due to septic shock. Due to her sudden decline, a broad work-up was initiated that ruled out spontaneous bacterial peritonitis, pneumonia, septic arthritis, or urine infection. Echocardiogram showed a moderate-sized loculated pericardial effusion with fibrinous material and a pericardial density. Blood cultures were positive for MRSA. The pericardial effusion progressed, causing tamponade, treated with pericardiocentesis. The results of pericardial culture revealed MRSA, and the treatment plan was IV vancomycin for 6 weeks. The patient unfortunately passed due to complications of cirrhosis, likely complicated by MRSA pericarditis.

Our patient had been hospitalized for one month when she developed sudden onset dyspnea, tachypnea, and hypotension. She had abdominal pain, edema, and lower extremity pain, but no chest pain. Furthermore she had no jugular venous distension or muffled heart sounds. These symptoms could be caused by advanced liver disease, therefore a cardiovascular etiology was not initially suspected. Echocardiography proved critically important in the diagnosis of pericardial effusion. A complicating factor in the current case is the MRSA blood stream infection, which was believed to be the cause of pericarditis and subsequent pericardial effusion and tamponade. It is unknown whether earlier identification and intervention would have resulted in a different outcome, however this case highlights that consideration of pericardial effusion in patients with cirrhosis is warranted. Timothy Smith, MD Category: Clinical Vignette

Recognizing Tick-Borne Relapsing Fever in New Mexico

Tick-borne relapsing fever (TBRF), a spirochetal infection caused by Borrelia species, is an infrequently recognized cause of febrile illness across the Western United States. We present a case highlighting the diagnostic considerations for clinicians evaluating the febrile patient in whom TBRF may be suspected. These considerations are vital as TBRF reporting is required in New Mexico to ensure local source control.

A previously healthy 67 year-old Native American male was transferred to our facility from an outlying hospital in western Arizona for evaluation and treatment of presumptive HantaVirus Pulmonary Syndrome (HPS). The patient originally presented with 6 days of dyspnea accompanied by a dry, non-productive cough in addition to a one month history of persistent subjective fevers accompanied by non-specific, generalized weakness. Patient denied sick contacts and ROS was non-contributory. Patient was a sheepherder living a traditional Navajo hogan in western New Mexico. Upon presentation, patient had a temperature of 103 and his physical examination was relevant for rigors, respiratory distress, tachypnea, and intercostal retractions. Initial labs revealed a WBC of 8.5, hemoglobin of 11g/dL and a platelet count of 22,000/mm3. A peripheral blood smear was completed to elucidate the cause of patient’s thrombocytopenia, and to evaluate for diagnostic criteria suggestive of HPS. Upon arrival to our institution, patient was empirically treated for community acquired pneumonia. One day after admission to our facility, the care team was notified the patient’s original blood smear demonstrated spirochetal organisms. Patient was subsequently transitioned to Doxycycline for empiric treatment of TBRF, and within 4 days patient’s symptoms had resolved and his platelet count increased to 150,000/mm3. Patient was discharged one day later with a 21-day course of Doxycycline. Patient’s blood cultures, respiratory virus panel, and sputum cultures (w/ testing for acid-fast bacilli) were all negative.

The Borrelia spirochete is most commonly transmitted by the Ornithodoros tick, which typically inoculates human hosts at night, feeding for 30 minutes or less, and frequently leaves little to no trace of a bite, accounting for the low rate of patient recognition of infectious vector. Patients may present between febrile periods and complain of vague generalized symptoms including headache, myalgia, chills, nausea, arthralgia, vomiting, and abdominal pain. It is important for local providers to consider TBRF in their differential in patients with risk factors for exposure, and obtain blood cultures and peripheral smear for the diagnosis. Without treatment, fatality rates are close to 10%. Jarisch-Herxheimer reaction is a complication that may occur in up to 54% of patients after initiation of antibiotics in those infected with spirochetes and is another important consideration that providers may miss if TBRF is not on the differential diagnoses. Kristen Gonzales, MD Category: Clinical Vignette

Malignant Insulinoma: A Rare Cause of Recurrent Hypoglycemia

Background: Hypoglycemia is a debilitating condition that may have potentially fatal outcomes if unrecognized. Clinical manifestations can range from classic autonomic symptoms to coma. Insulinomas are the most common cause of hypoglycemia related to endogenous insulin production; however, in the general population, they are extremely rare, having a reported prevalence of only 1-4 people per million. Furthermore, of these rare neoplasms, only 7-10% are malignant. While prognosis for benign insulinomas remains good, that for malignant insulinomas is much poorer. Medical management remains the cornerstone of treatment for malignant insulinomas if disease is unresectable, and vigilant monitoring for hypoglycemia and avoidance of symptoms remains of utmost importance. Continuous glucose monitoring (CGM) has been described in the literature as an innovative method of optimizing management of these patients, and it can potentially contribute to significant improvement in overall prognosis. We present a case of malignant insulinoma which has been successfully managed long-term with both medical intervention and CGM with an overall relative reduction in hypoglycemia- related adverse events.

Case Report: 77 year old female diagnosed with a benign insulinoma at age 44 who underwent surgical resection via partial pancreatectomy and exhibited a favorable clinical response. Six years later she developed recurrent episodes of hypoglycemia and was confirmed to have a single hepatic lesion of metastasis. Surgical excision was performed, and the patient remained asymptomatic for approximately 10 years. At age 70 she again became symptomatic and was found to have diffuse metastatic disease, thereby making her disease inoperable. Medical management was implemented, and the patient was started on CGM. Diazoxide has been most effective in preventing severe hypoglycemia, and CGM has played an integral role in managing her symptoms. Both her quality of life and prognosis have significantly improved with its use, as she is now 40 years out from the time of initial diagnosis.

Discussion: While benign insulinomas are the most common neuroendocrine tumors of the pancreas with a relatively good prognosis due to curative interventions (88% 10-year survival), conversion to malignant insulinomas remains an extremely rare phenomenon that poses significant morbidity and mortality to affected patients. Ten-year survival for malignant insulinomas has been reported to be roughly 29%. However, use of CGM for management of hypoglycemia, perhaps one of the most significant risk factors contributing to morbidity, was first reported in 2008, and the case reports documenting its use have demonstrated very positive outcomes. Our patient is one among few reported cases in the literature exhibiting prolonged survival due to the use of a multimodal medical approach which is enhanced significantly by the use of CGM. Ziyang Liu, MD Category: Clinical Vignette

An Unusual Cause of Hepatic Abscess in a Patient with Diverticulitis

A 55 year old frequent traveler to Mexico with no significant PMH presented with one year history of RUQ abdominal pain, intermittent fever and night sweats and was found to have 2 large cystic fluid collections in his liver on abdominal CT. The pain started as a sharp, stabbing 3-8/10 daily pain that gradually changed to a dull pain with associated soreness in the area. The pain worsened with meals and activity and had gotten worse over the previous 2-3 month. He had also recently developed anorexia, nausea and a 20 lbs weight loss. His laboratory findings showed leukocytosis, normocytic anemia, elevated alkaline phosphatase, mildly elevated AST and ALT, low albumin, and normal bilirubin. Abdominal CT showed large lobulated intrahepatic rim-enhancing fluid collections in the right hepatic lobe with marginal edema measuring 7.5 x 12.1 cm and an additional round fluid collection measuring 3.8 cm with ill-defined margin as well as mild pericolonic inflammatory stranding adjacent to the ascending colon suggestive of diverticulitis. The patient was empirically treated with intravenous ceftriaxone and metronidazole to cover for both pyogenic and amebic abscesses. After 4 days of minimal improvement, he underwent US-guided catheter drainage of the largest cyst for both diagnostic and therapeutic purposes. Ceftriaxone was discontinued after amebic species were confirmed in both abscess fluid and stool samples. He was then started on ciprofloxacin for broaden coverage for diverticulitis. Patient rapidly improved after abscess drainage and became free of symptoms after 5 days. After completing 14 day course of metronidazole for both the abscess and the diverticulitis, he was started on paromomycin for 7 days to eliminate the intraluminal cysts. Amebic hepatic abscesses are most commonly caused by E. histolytica.

While rare in the United States, E. histolytica is the second most common cause of parasitic death in the world, followed by malaria. Hepatic abscess is one of the most common extraintestinal manifestations of E. histolytica. In hepatic abscesses, the clinical presentation of pyogenic and amebic abscesses are indistinguishable. We often must rely on extrahepatic signs and symptoms, epidemiologic risk factors and other laboratory testing to differentiate between the two. Our case presents a rare case of co-occurring diverticulitis and amebic hepatic abscess. As a known risk factor for pyogenic hepatic abscess, the presence of diverticulitis in a patient with known risk factors for amebic infections significantly complicated the diagnosis of the etiology of his hepatic abscess. Differentiating between pyogenic and amebic hepatic abscess is important for the treatment both medically and surgically as seen in this patient. Sarah Burns, MD Category: Clinical Vignette

Taking a Stab at the Diagnosis

Heart failure with preserved ejection fraction comprises 50% of new onset heart failure cases and is a diagnosis of exclusion. Cardiac amyloidosis, an uncommon disorder with approximately 2000 new cases occurring in the USA yearly, is a cause of infiltrative cardiomyopathy which can present clinically as HFpEF.

A 65 year old female recently discharged from an outside hospital presented to the ED with 24 hours of worsening dyspnea associated with dizziness. Cardiac work up at the outside facility included normal cardiac catheterization and an echocardiogram showing normal ejection fraction. She was diagnosed with new onset heart failure with preserved ejection fraction and discharged on bumex, carvedilol, losartan, rosuvastatin, and warfarin. On presentation, she was afebrile, hypotensive (systolics between 80 and 100 mmHg) and tachycardic (pulse to 101 beats per minute), with normal oxygen saturation on room air. Physical exam was significant for periorbital purpura, bibasilar crackles and lower extremity edema. Labs revealed hemoglobin of 16.6, hematocrit of 51, albumin of 1.7, INR of 5.73, N-terminal proBNP of 12698, initial troponin of 0.828, and repeated troponin of 0.897. Electrocardiogram showed low voltage and Q waves in the anterior, septal and inferior leads. Repeat transthoracic echocardiogram demonstrated severe concentric left ventricular hypertrophy, ejection fraction of 46-50%, mildly reduced left ventricular systolic function, transmitral spectral Doppler flow pattern suggestive of restrictive filling, mild right ventricular hypertrophy, and moderate pericardial effusion without tamponade. A cardiac MRI was obtained and showed diffuse thickening of the left and right ventricles with markedly abnormal gadolinium contrast dynamics and diffusely delayed myocardial gadolinium uptake indicative of an infiltrative process. An endomyocardial biopsy stained with congo red demonstrated amyloidosis. Further staining was positive for lambda light chains. Urinalysis revealed proteinuria and serum lambda light chains were significantly elevated. Bone marrow biopsy revealed plasma cell myeloma positive for lambda light chains. Treatment consisted of diuresis and discontinuation of beta blockers and angiotensin receptor blockers as scant evidence exists for use in cardiac amyloidosis. The patient’s dyspnea improved with diuresis and she was referred to hematology and oncology for possible initiation of treatment of multiple myeloma.

When determining the underlying etiology of HFpEF, awareness of the various pathologies and a systematic approach to ruling out these pathologies is essential for proper diagnosis. Deconditioning, constrictive pericarditis, infiltrative processes (including amyloidosis, sarcoidosis and hemochromatosis), valvular disease, CAD, high output failure including thyrotoxicosis, and RV myopathy must be considered in the evaluation of new onset HFpEF. When amyloidosis is confirmed, determination of the type of amyloid is critical as treatment and prognosis varies significantly between various types. At the present time, the patient has a 5 year survival rate of approximately 8% based upon NT-proBNP and troponin as predicted by the Mayo Stage model. Lauren Liaboe, MD Category: Clinical Vignette

Leaching Liver Lesions: A Case of Invasive Klebsiella Pneumoniae Liver Abscess Syndrome

Invasive Klebsiella pneumoniae liver abscesses syndrome (IKPLAS) is a rare clinical disease entity defined as a liver abscess and disseminated Klebsiella infection. It is often seen in patients of Asian descent and is increasing in prevalence within the United States.

An otherwise healthy 42-year-old Vietnamese man who immigrated to the United States six years prior presented to the emergency department with a nine-day history of back pain. The patient reported his pain worsened acutely just prior to presentation when lifting a heavy object. He also described numbness of the left leg. At presentation, the patient was septic. Because of this, a MRI of the lumbar spine was obtained which demonstrated multiple paraspinal and gluteal region abscesses. A chest CT demonstrated a 2cm right hepatic lobe hypoattenuating lesion suggestive of an abscess as well as multiple pulmonary nodules with peripheral and upper lobe predominance. Blood cultures drawn prior to initiation of antibiotics grew out Klebsiella pneumoniae. Given the patient’s ethnic background and the organism isolated, the liver lesion was suspected as the primary abscess, with hematogenous dissemination to the lungs, paraspinal and gluteal regions, this being consistent with IKPLAS. The patient underwent drainage of the piriformis muscle abscess which also yielded Klebsiella pneumoniae. When cultures returned positive for Klebsiella pneumoniae, the antibiotic regimen was narrowed to ceftriaxone based on organism susceptibility. Despite appropriate antibiotic therapy, he went on to develop further abscesses as well osteomyelitis of the L1 and L2 vertebrae. He underwent subsequent abscess drainage after which the patient defervesced and his back pain improved. The patient was eventually discharged on ceftriaxone 2gm every 12 hours and received a total of eight weeks of antibiotics.

IKPLAS is rare but increasingly prevalent syndrome associated with a high degree of morbidity and mortality. It should be considered in septic patients who are found to have liver abscesses and are of Asian descent. Joseph Eleid, MD Category: Clinical Vignette

It''s Not Pancreatitis: Persistently Elevated Lipase Secondary to Macrolipasemia

Lipase detected in the serum is typically used in the diagnosis of pancreatitis. There is, however, an entity known as macrolipasemia which is thought to be a non-pancreatic-derived protein-bound macromolecule. Macrolipase has been associated with various disease processes such as Crohn disease, cirrhosis, non-Hodgkin Lymphoma, celiac disease, and SLE. These associations have only been described in case reports. Macrolipasemia has no known etiology.

A 54-year-old Vietnamese woman with no significant past medical history presented with significant weight loss, abdominal fullness and pain, and anorexia. These symptoms had been present intermittently for the prior 2-3 years, but had recently become constant and severe. Initial workup showed a lipase elevated over 4000 suggestive of pancreatitis. Abdominal imaging was negative and further diagnostic workup did not reveal an etiology for pancreatitis. Patient was given bowel rest and IV fluids, showed improvement, and was discharged home. The patient returned 48 hours later with the same symptoms as her initial presentation. This time she did not show a significant response to typical pancreatitis treatment. An extended workup to determine an etiology of the elevated lipase and abdominal pain was then done with the assistance of Gastroenterology and Surgery. The interdisciplinary conclusion was that her presentation was inconsistent with pancreatitis, but the cause of the abdominal pain remained unknown. Incidentally, a biopsy obtained during an upper endoscopy showed H. pylori; it was subsequently eradicated without resolution of symptoms. While investigating rare causes of persistently elevated lipase, we decided to send serum to test for the presence of macrolipase. The result of this test showed that 99.1% of patient’s serum lipase was macrolipase, which is consistent with macrolipasemia. To date, the etiology of patient’s elevated lipase and abdominal symptoms remains unknown. She was subsequently diagnosed with monoclonal gammopathy of undetermined significance (MGUS), but as the name implies, this is of undetermined significance.

We present a case of macrolipasemia of unknown etiology. The delay in discovering that the lipase elevation was nonpancreatic in origin resulted in a protracted and expensive workup, which could have been avoided or more focused, had the detection of macrolipase been sooner. Over the course of multiple hospitalizations, the patient received 4 abdominal CT scans, several ultrasounds, 2 MRIs, an EGD, a colonoscopy, a HIDA scan, a gastric emptying study, and a small bowel series. Though macrolipasemia is an exceedingly rare clinical entity that has only been described in case reports, it remains as an important part of the differential diagnosis in a patient with persistently elevated lipase in the absence of pancreatitis. Martha Mapalo, MD Category: Clinical Vignette

An Uncommon Complication of Severe Hypertension

Posterior reversible encephalopathy syndrome (PRES) is a potentially reversible clinicoradiologic syndrome characterized by headache, mental confusion, visual disturbances and associated with characteristic posterior cerebral lesions on radiological imaging. Prompt treatment of this condition is mandatory to avoid severe irreversible complications.

A 63 year old woman with history of severe hypertension was found unresponsive at a nursing facility. By arrival to ED, she was awake, but disoriented to time and place. Her blood pressure was elevated at 202/95, the rest of her vitals were normal. She had no focal neurological deficits; however she did complain of severe headache and later, blurred vision. CT scan showed new hypoattenuation of the white matter in the left cerebrum semiovale, concerning for acute subacute ischemia. There was concern for stroke, however her National Institutes of Health Stroke Scale score was mild and she had been on heparin for DVT prophylaxis, therefore did not get thrombolysed. A lumbar puncture showed elevated protein. She had a moderately abnormal EEG with diffuse cerebral dysfunction, but no epileptiform activity. Repeat CT the next day done to confirm an ischemic event showed continued mild edema in the high left cerebral hemisphere, and new finding of edema in the posterior parietal lobes bilaterally; to consider PRES. Over the next few days, her mentation returned to normal, but she continued to complain of severe frontal headache and blurred vision, BP was managed with amlodipine and carvedilol, later a was added. Fundoscopic exam was unremarkable, however on confrontation she did have right superior quadrantanopia. Blurry vision was attributed to PRES By the time of discharge, was at baseline functionally, blood pressure better control, had residual headache and blurry vision.

Discussion: This case highlights the importance of considering PRES in patients presenting with severe hypertension, headache, alteration in mentation, seizures and/or visual disturbances. It uncommonly presents with neurological deficits. PRES has been described in all ages, also in pregnant women, patients on immunosuppressant medication, renal disease, hypertension or autoimmune diseases; therefore cuts across all medical disciplines. It’s important to recognize and treat it promptly, because it is potentially reversible, however if not, can lead to fatal outcomes or long term sequelae. Another lesson learnt from this case is that PRES may be misdiagnosed as TIA or stroke, for which management would include ‘permissive hypertension’ in the acute setting, but in PRES aggressive management of blood pressure if hypertension is present, is necessary. Jan Irum, MD Category: Clinical Vignette

Vitamin B12 deficiency Masquerading as TTP

Introduction: Undiagnosed pernicious anemia is common in elderly population and can lead to many sequelae including neurologic deficits, hematologic abnormalities, and is even associated with cancer.

This case describes a patient who presented with severe neurologic deficits and an apparent hemolytic anemia which was found to be secondary to B12 deficiency. The effects of b12 deficiency are far reaching and the neurological effects tend to be more permanent which makes it more important to be diagnosed early. Case 81yoM with past medical history of BPH brought in by family to the emergency department for concerns of worsening mental status, severe weakness, anorexia and general failure to thrive. Initially a severe hemolytic anemia secondary to TTP was suspected because of severe anemia and thrombocytopenia, elevated LDH and low haptoglobin,schistocytes on smear,elevated creatinine and altered mental status. Furthermore, it was noted that the patient was unable to swallow liquids or solids. Peripheral smear suggested schistocytes and Hypersegmented neutrophils, MCV was noted to be elevated at 139. Further evaluation did not suggest hemolysis and initial B12 levels were unmeasurable. Despite severe anemia, we were unable to transfuse the patient because he was thought Jehovah’s witness by his family. Intrinsic factor blocking Ab was sent and came positive suggesting long-standing pernicious anemia. After administration of B12,folate and IV iron , pt experienced mild improvement in cognition, but remained with severe deficits. Hgb improved minimally. Repeat swallow studies noted complete inability to swallow liquids and solids, ultimately an esophageal gastrograffin was performed and this demonstrated severe stenosis at the level of the LES with irregular borders highly suggestive of malignancy. Considering the known association of pernicious anemia with malignancy, gastric cancer was highly suspected, but confirmatory biopsy could not be performed as patient had severe anemia. Ultimately the family decided to take the patient home for hospice care without further intervention.

Conclusion: Pernicious anemia is very common in the elderly and if undiagnosed can lead to severe consequences including neurologic deficit, severe anemia/hemolysis and even cancer. This underscores the importance of high clinical suspicion in the appropriate setting and early treatment to prevent these worse outcomes. Shira Amdur, MD Category: Clinical Vignette

A Case of TB-induced Hypersensitivity

Erythema induratum (EI), or nodular vasculitis, is a hypersensitivity reaction often, but not exclusively, associated with Mycobacterium tuberculosis infection. It presents clinically as painful, recurrent violaceous nodules and plaques on the lower extremities that then leave a scar hyperpigmentation. It can closely resemble erythema nodosum and is distinguished histopathologically.

A 53-year-old man who immigrated to the United States from Vietnam approximately one year prior presented to his primary care physician with a rash on his lower legs. He described a one- month history of painful, red bumps initially on his calves, which spread anteriorly. He rated the pain 9/10 and complained that it kept him up at night. Ibuprofen provided some relief and oxycodone provided no relief. He was given a course of Keflex but his rash did not respond. He also complained of fevers, chills, fatigue, joint pain and swelling (ankles, MCPs, and PIPs). He denied cough, hemoptysis or night sweats. He also denied recent travel or sick contacts, including known exposure to anyone with tuberculosis. Patient was referred to Rheumatology at which time he was considered to have erythema nodosum and hydroxychloroquine was prescribed. Several labs were ordered including a QuantiFERON Gold, which came back reactive. Other abnormal labs included elevated ESR, CRP, C4, and a differential significant for an eosinophilia. A recent chest x-ray was negative. Patient was referred to the Department of Health for latent tuberculosis, as well as to Dermatology for skin biopsy. Biopsy was undertaken and showed septal and lobular panniculitis with granulomatous inflammation, fat necrosis, caseating necrosis, and vascular damage (a deep dermal vessel had fibrinoid necrosis), all consistent with EI. As a result, the patient was advised to stop taking the hydroxychloroquine and was counseled on the importance of compliance with his anti-tuberculosis regimen. Following this, the patient was treated for latent TB, and his EI significantly improved.

This case illustrates a fascinating example of a cutaneous reaction to M. tuberculosis. Although this patient did not display any classic symptoms associated with TB—he had no pulmonary involvement—his underlying illness was revealed by a QuantiFERON Gold prior to starting strong immunosuppressants. Erythema induratum is easily misidentified as erythema nodosum, and the biopsy is crucial in distinguishing the two. As treatment differs for these two types of panniculitis, it is critical to correctly identify the condition. Susan Showers, MD Category: Clinical Vignette

A Clinically Important and Novel Side Effect of Sumatriptan: A case report

This case reminds us to be mindful of all potential side effects of medications given in the inpatient setting. Sumatriptan potentially confounded the care of our patient by causing elevated lactic acid in the absence of sepsis.

A 33 year old male with past medical history of migraines, pulmonary HTN, and ongoing IV drug use, with recent tibial fracture who underwent ORIF which was complicated by hardware infection requiring long term Nafcillin treatment, was admitted from an outpatient antibiotic infusion center for treatment of Acinetobacter bacteremia and Candida fungemia. His hospitalization was complicated by multifocal pneumonia and a brief MICU stay for hypoxic respiratory failure. He improved clinically and was transferred back to the floor where daily lactates, which were drawn per protocol, remained near 2.0. On day 10 of the hospitalization he reported a migraine and requested Sumatriptan from the overnight covering physician. Shortly thereafter, he became agitated with BP of 160/102, HR 129, and O2 sat 83%. The abnormal vital signs lasted several hours and the overnight physician evaluated the patient who reported anxiety, vague chest discomfort and mild abdominal pain. Troponin was found to be mildly elevated at 0.5 without any ischemic EKG changes. Lactate was critically high at 13.7. Repeat lactate was 2.1 after 1 liter normal saline. The rapid decrease in lactate led us to believe that it was more likely a transient side effect of medication rather than a consequence of ongoing severe sepsis. Blood cultures drawn were negative at 5 days further supporting this hypothesis. Moreover, this patient never had documented hypotension during the episode of transient lactic acidosis. The patient’s abdominal pain quickly resolved without intervention making mesenteric ischemia or ischemic colitis unlikely. Transthoracic echocardiogram performed 3 days later showed no findings to suggest myocardial ischemia. Thus, the acute elevation in lactate was presumed to be due to the Sumatriptan administration.

Multiple medications have been associated with a type B2 lactic acidosis although the exact mechanism is unclear. Type B lactic acidosis is usually quickly reversible which differs from Type A lactic acidosis which is due to hypoperfusion and tissue hypoxia. While Sumatriptan has been associated with rare cases of mesenteric and cardiac ischemia, it is hypothesized that our patient’s transient lactic acidosis was a Type B lactic acidosis side effect of the medication, which to our knowledge, has not been reported before. Based on this case, we recommend careful consideration when giving Sumatriptan for the treatment of migraines in the inpatient setting. Christina Rea, MD Category: Clinical Vignette

Fever of Unknown Origin in an Immunocompetent Adult Due to Cytomegalovirus

Fever of unknown origin (FUO) is defined as a prolonged febrile illness with a temperature greater than 101 degrees Fahrenheit that remains undiagnosed for more than three weeks. Malignancy, infections, and autoimmune etiologies are the most common causes of FUO. All cases of FUO are associated with a high mortality, estimated to be between 22-52%. Thus, it is essential for physicians to promptly and effectively diagnose and treat FUO. We present to you a rare case of FUO secondary to cytomegalovirus (CMV) viremia in an immunocompetent host.

A 48-year old healthy male presented with a 6-week history of fevers, as high as 102.5 degrees Fahrenheit. Fevers were associated with night sweats, severe frontal headaches, green nasal discharge, blisters on lips, a maculopapular rash on arms, photophobia, blurry vision, myalgias and stiff neck. Outpatient management consisted of four courses of antibiotics with no improvement. Pertinent labs on admission were leukocytosis to 30 with atypical lymphocytosis and monocytosis, as well as transaminitis. Lumbar Puncture showed no signs of infection. Further work up included Blood Cultures, Urine Culture, AFB smear, SPEP, Coccidiomycosis, Blastomycosis, Histoplasmosis , Cryptococcus, West Nile Virus, Brucella, HIV serology, autoimmune panel, and CT Head and Chest – all of which were negative. Given atypical lymphocytosis and the overall clinical picture, CMV PCR was sent and was found to be positive with extremely high titers (47,000 copies per ml). The patient was diagnosed with CMV mononucleosis syndrome and treatment was initiated with valgancyclovir . On outpatient follow up, the patient’s symptoms had resolved and his CMV viral load was undetectable within four weeks of treatment with valgancyclovir.

Viral etiologies, especially CMV, are uncommon causes of FUO. CMV viremia causing FUO in an immunocompetent host has rarely been reported in the literature. A French Study which reported all FUO cases between 2000 to 2012 documented only one case of CMV viremia. Despite being rare, CMV should be considered if driven by clinical suspicion as it is relatively easy to diagnose and treat. This can decrease both health care cost as well as patient discomfort and distress from prolonged and invasive work-ups. Emily Hanson, MD Category: Clinical Vignette

Diastolic Dysfunction in Friedreich’s Ataxia

Background: The leading cause of death in Friedreich’s Ataxia (FA) is due to cardiomyopathy, which predisposes patients to heart failure and . As such, the typical life expectancy in these young adults is 29-38 years. A retrospective analysis of a large FA registry has shown that left ventricular systolic dysfunction is predictive of poor outcomes (1), but diastolic dysfunction has received insufficient attention in the literature, perhaps owing to difficulty in diagnosis.

Case: A 25-year-old woman recently diagnosed with FA presented with 6 months of increasing exertional shortness of breath, chest pressure and tightness radiating to her neck. She also had been waking up short of breath. An electrocardiogram was significant for right axis deviation, poor R wave progression and nonspecific ST segment changes. A transthoracic echocardiogram demonstrated normal systolic function, with an ejection fraction (EF) >55%. However, the transmitral Doppler E/A ratio of 1.8 suggested pseudonormalization with elevated diastolic pressures, as did a mitral valve “B-bump” on M-mode. The patient subsequently underwent cardiac catheterization, which revealed angiographically normal coronary arteries but severely elevated filling pressures, with a left ventricular end-diastolic pressure of 28 mmHg.

Discussion: This patient presented with a clinical syndrome consistent with heart failure, confirmed ultimately by measurement of significantly elevated left ventricular filling pressures. Elevated filling pressures may also cause coronary microvascular dysfunction and myocardial injury (2), and as such lead to an anginal syndrome. The prevalence and severity of diastolic dysfunction in patients with FA is unknown. Recent models for evaluating extent of cardiac involvement in patients with FA have shown left ventricular hypertrophy and EF to be strong indicators of cardiomyopathy progression. However, diastolic parameters were incompletely characterized and not included in analysis (1). Nearly 50% of patients with heart failure have preserved EF, with outcomes that are similar to those with reduced EF (3). Indicators of diastolic dysfunction, such as E/A and E/e’ ratios and presence of B-bump, can be identified on echocardiogram, and may play an important role in identifying higher risk patients with cardiomyopathy due to Friedreich’s Ataxia. Pradeep Mitta, MD Category: Clinical Vignette

Zero to Sixty in 48 Hours

Cirrhosis is a known cause of thrombocytopenia but it is important to consider other etiologies when the degree of thrombocytopenia is severe, especially in light of impending life-threatening bleeding. One must always maintain a low threshold for additional diagnostic entities when patients present acutely and confirmatory testing reveals profound thrombocytopenia.

A 34-year-old man with cirrhosis secondary to Hepatitis C and alcohol abuse presented with persistent bleeding from preexisting oral ulcers and . Patient denied melena, hematemesis or hematochezia. His past medical history was significant for pancytopenia secondary to cirrhosis, active hepatitis C infection and hypersplenism. He denied any recent change in his medications nor taking any herbal medications or supplements. Vital signs were normal on admission. Physical examination was positive for dried blood on the lips and hepatosplenomegaly. Lab work revealed a platelet count of 0 with chronic leukopenia and anemia. His baseline platelet count is approximately 35,000. Urine analysis indicated gross blood. Coagulation workup was not suggestive of Disseminated Intravascular Coagulation (DIC). Peripheral smear was significant for complete lack of platelets without schistocytes. He was started on daily platelet transfusions with minimal change in his platelet count. A diagnosis of secondary Immune Thrombocytopenic Purpura (ITP) was made and therapy was initiated with intravenous immunoglobulin (IVIG) and dexamethasone. His platelet count failed to improve with worsening hematuria. He also received Rituximab, Romiplostim infusions and high dose methylprednisolone. The patient underwent splenic artery embolization three times. In spite of all efforts he continued to have hematuria and bleeding from intravenous lines with only transient rise in counts. He was taken for laparoscopic splenectomy with a platelet count of 35,000; following which the bleeding subsided and his platelet count improved to 100,000. Patient had a complicated hospital course but was eventually discharged home and currently his platelet counts are within normal limits. This patient appeared to have developed secondary ITP from his active Hepatitis C. Though he had chronic thrombocytopenia from cirrhosis and splenomegaly, it would be unusual to see this degree of platelet drop from these causes alone.

ITP is a diagnosis of exclusion and bleeding is usually not proportionate to level of thrombocytopenia as in this patient. This case illustrates the fact that a clinician must have a low threshold for expanding the differential diagnosis of thrombocytopenia, especially diagnoses that are likely to harm the patient such as Thrombotic Thrombocytopenic Purpura, Disseminated Intravascular Coagulation and ITP. This case also demonstrates the challenging nature of managing severe refractory ITP. Splenectomy is the preferred therapy for patients with ITP who are refractory to first-line therapy with glucocorticoids or IVIG and is shown to cause sustained remission in two-thirds of patients. Youngh Ho Kim, MD Category: Clinical Vignette

When has a Separation Anxiety Disorder

Introduction: Electrolyte abnormalities coupled with hypertension and acid-base disorders, especially in young patients with normal renal function, could signify secondary hypertension.

Case report: A 32 year-old Hispanic male was referred to clinic with hypertension and hyperkalemia. Physical examination revealed a BP of 170/110 mmHg bilaterally, pulse of 72, soft abdomen with no renal bruits, and no edema. Laboratory findings were significant for a Cr of 0.99 mg/dL, K, Cl and CO2 of 6.6, 113 and 18 mEq/L respectively and a spot urine K/Cr ratio of 1.2. Suppression of renin aldosterone system was also noted. The constellation of findings of hypertension, hypobicarbonatemia and inappropriate renal K handling in setting of hyperkalemia pointed towards pseudo-hypoaldosteronisim II (PHA-II). Since genetic testing is often costly and not cost-effective, the patient was started on chlorthalidone which normalized his blood pressure and electrolyte abnormalities.

Discussion: Gordon described a syndrome of hyperkalemia, hypertension and metabolic acidosis characterized by sodium (Na) retention and inability of the kidneys to excrete potassium (K) in patients with preserved glomerular filtration rate (GFR). Potassium excretion requires a high collecting duct (CD) tubular flow rate, a lumen negative voltage and presence of K channels. It is postulated that the human body has evolved to preserve Na and excrete K as most of the naturally occurring foods are low in Na and high in K. This is achieved by regulatory enzymes referred to as “with-no-K (with K referring lysine, WNK)” that regulate the activity of Na-Cl co-transporter (NCC) in DCT and K channels in CD. In between meals, the human body tries to conserve Na. This is achieved by the presence of WNK-3 in distal convoluted tubular (DCT) cells which promotes the expression of NCC. A diet high in K results in high aldosterone levels as well as suppression of WNK-3 and NCC by WNK-4 which in turn leads to lumen negative voltage, increased distal Na delivery and expression of K channels in the CD. These changes lead to excretion of K load after which WNK-4 is inhibited by WNK-1 that results in reactivation of WNK-3 and Na preservation state. PHA-II is a condition that could be due to a loss of function mutation of WNK-4 or gain of function mutation of WNK-1. This causes Na retention and hypertension that result in suppression of the renin/aldosterone axis and hyperkalemia. Metabolic acidosis ensues primarily from decreased urinary ammonium excretion in setting of hyperkalemia and hypoaldosteronism. The main stay of therapy is as they block NCC which results in Na wasting, increased aldosterone and K excretion that leads to normalization of blood pressure and electrolyte abnormalities Kristen Lytle, MD Category: Clinical Vignette

Dramatic Gangrene: A Case of Multi-Digit Gangrene Syndrome

Multiple digits gangrene is a rare occurrence. Necessity for an extensive work up is warranted considering the multitude of etiologies and gravity of this condition. We are presenting a case of multi-digit gangrene that was challenging from a diagnostic point of view.

A 55 year old male with a history of traumatic brain injury and disorder was admitted for dry gangrene of multiple digits on his hands and feet, hypoxia and acute heart failure. The gangrene had developed in the previous week without signs of intercurrent infection or hemodynamic compromise. In addition, he was found to have anemia and thrombocytopenia. Imaging including CT angiography of chest, abdomen and extremities revealed a right lung apical mass, no pulmonary embolism, and no atheromatous changes or vascular occlusions on extremities. The initial diagnosis of thromboangiitis obliterans was not satisfying because of the very rapid development, discrepancies with angiographic findings, and history of no tobacco use. At this point, focus of investigation was centered on possible paraneoplastic syndrome, vasculitis or thromboembolic disease. Workup for possible malignancy, which included imaging, bronchoscopy, apical mass biopsy, and later upper endoscopy and colonoscopy was negative. Rheumatology panel, which included c- and p-ANCA, ANA, hepatitis C serology, and scleroderma antibodies was negative for vasculitis; however, the diagnosis of antiphospolipid syndrome was eventually established by positive lupus like inhibitor and increased cardiolipin IgM level. The patient was started on life-long oral anticoagulation and discharged home. Unfortunately, his further course was complicated by wet gangrene of the right foot and further progression of dry gangrene of his fingers. On next admission, he had a right below knee amputation with pathology showing medium and large arterial thromboses. Later, the patient died at home from unrelated causes.

Multiple digits’ gangrene is a dramatic syndrome with a challenging nature of diagnosis. Major entities in differential diagnosis are thrombangiitis obliterans, various vasculitides, neoplastic syndrome, symmetric peripheral gangrene, and antiphospholipid syndrome, which a few of these are not commonly seen in general and hospital practice. Multiple digits’ gangrene is uncommon manifestation of antiphospholipid syndrome, and we believe that knowledge of this devastating thromboembolic complication would be of benefit for health care providers, from students to seasoned clinicians. Joshua Duchesne, MD Category: Research

Developing Specific Identifers for a New Classification System And Diagnostic Differention For Cocaine-Induced Vasculitis: Initial Population Studies

PURPOSE: To determine demographic and clinical aspects of cocaine-associated vasculitis (C AV) and compare these variables with non-cocaine-associated vasculitis (non-CAV).

METHODS: In an IRB-approved exempt study 76 consecutively encountered patients with definite vasculitis cared for by the UNM Rheumatology Division were identified for retrospective examination of clinical features, findings, and demographics including a standardized battery of immunologic and rheumatologic examinations recorded in the EMR. 31 patients with CAV and 45 with non- CAV were characterized as immunologic findings (ANCA, PR3, MPO, ANA, DNA, HCV, cyroglobulins), clinical findings (including vascular imaging, biopsy, vasculitis rash, neuropathy, glomerulonephritis, pulmonary hemorrhages, etc), and demographics (age, gender, cocaine use, tobacco, alcohol, opiates, other drugs). Standard summary statistics (means, medians, proportions, odds ratios, confidence intervals) were calculated for cocaine ever (the dependent variable) and all potential predictor variables. Predictor variables were tested for strength of relationship with cocaine use ever, using univariate logistic regression. Models were fitted using maximum likelihood estimation. Since a large number of potential explanatory variables were investigated we used the Bonferroni method to avoid too large Type I error rate. Since we had 122 potential explanatory variables we divided 0.05 by 122 to achieve a critical p- value of 0.00041. Two tailed tests were used throughout.

RESULTS: Basic demographic were as follows: Mean age (CAV= 44, non-CAV= 51, P = 0.019), female gender (33%CAV, 67%non-CAV, P = 0.0001), cocaine use (CAV 100%, non- CAV0%, P = 0.0001). Major categories GPA (Wegener’s) (6%CAV, 22%non-CAV, P = 0.0001), MPA (microscopic polyangiitis) (71%CAV, 44%non-CAV, P = 0.0001), EPA (Churg-Strauss) (3%CAV, 7 %non-CAV, P = 0.0001), Takaysu’s arteritis (3%CAV,0 %non-CAV, P = 0.0001), and Giant cell (temporal arteritis) (0%CAV, 9 %non-CAV, P = 0.0001). In corrected comparisons, in CAV patients compared to non-CAV demonstrated a statistical increase in DNA (p=0.0003), P-ANCA (p=0.0011), and vasculitis disease activity (BVAS) (P=0.0001), but not c- ANCA (p=0.2995), and not MPO or PR3 (p>0.05). Further there were statistical differences in corrected P-values between (CAV and non-CAV) in the following variables: tobacco use (p=0.0001), ETOH (p=0.0001), opiate (p=0.0026), cannabis (p=0.0004), HCV PRC (p=0.002), lesions arms (p=0.0001), lesions legs (p=0.0001), lesions feet (p=0.0001), lesions trunk (p=0.0001).

CONCLUSIONS AND SIGNIFICANCE: CAV is characterized by younger age, male gender, excess of MPA, p-ANCA positivity, serologic overlap with SLE, substance abuse, extensive skin lesions, and greater disease activity (BVAS). This study will provide markers to help differentiate CAV from non-CAV in obtunded, recalcitrant, or disingenuous patients, and provide preliminary identifiers for a specific CAV classification within existing vasculitis classifications systems. Nhan Luu, MD Category: Clinical Vignette

Gitelman syndrome Masquerading as Chronic Hypomagnesemia

Gitelman syndrome is a heritable renal disorder characterized by hypomagnesemia, hypokalemia and hypocalciuria linked to an inactivating mutation of the gene encoding the thiazide sensitive Na-Cl- (NCCT) located on chromosome 16q. A relative low prevalence and varied presentations make Gitelman syndrome a diagnostic challenge.

A 63 year old woman with a history of chronic hypomagnesaemia and GERD presented to the outpatient renal clinic for further work up. She has a history of multiple admissions for diffuse muscle pain, weakness, leg , and . There was no history of fever, diarrhea, rash or abdominal pain. She reported having increase urinary frequency, but no other urinary tract symptoms. She took oxide 400 mg PO TID, omeprazole 40 mg PO Qday, carbonate 1 tab PO BID, and amelioride 5mg PO Qday. The family history and and childhood history were unremarkable. Physical examination revealed blood pressure 115/77 mmHg. The rest of the exam was benign. Renal ultrasound was normal and there was no evidence of . Urinalysis was unremarkable. Her past several chemistries were unremarkable except for persistent hypomagnesemia. However, during this clinical visit, her chemistry revealed hypokalemia, , hypocalcemia, hypophosphatemia, and hypomagnesemia. Omeprazole was held due to its ability to reduce GI absorption of magneseium. On further evaluation, her Ca/Cr ratio was low at 0.07, reflecting hypocalciuria. Her fractional excretion of magnesium was 11%, reflecting a significant renal magnesium wasting. Renin (19) and aldosterone (141) both came back high with ARR ratio at 7, reflecting salt wasting-induced activation of the RAAS. Subsequently, she was treated with magnesium and potassium supplements and . After several weeks of treatment, her hypokalemia, metabolic alkalosis, and hypophosphatemia all resolved. Although hypomagnesemia significantly improved, full normalization of serum magnesium level was difficult to achieve because high doses of magnesium cause diarrhea and GI loss of magnesium.

The chronic salt wasting state of Gitelman syndrome is responsible for the host of electrolyte abnormalities. The loss of sodium reabsorption at the distal tubules (DCT) results in increased Na+ delivery and absorption through the epithelial sodium channel (ENac). This increases the negative charge in the tubular lumen that will stimulate potassium (K+) and hydrogen ion (H+) secretion, resulting in hypokalemia and hypochloremic metabolic alkalosis. The hypercalcemia and hypocalciuria seen in Gitelman syndrome are due to volume contraction induced by increase in sodium (Na+) and calcium (Ca++) reabsorption at the proximal tubules. The magnesium wasting in Gitelman is be due to salt wasting induced by volume contraction that stimulates aldosterone release, resulting in downregulation of the magnesium channel TRPM6. This case illustrates the myriad ways Gitelman syndrome can present. Timely recognition of Gitelman syndrome is important for institution of appropriate therapy and minimization of long- term complication of hypomagnesemia. Kavitha Ganta, MD Category: Clinical Vignette

Hypokalemia: A Common Manifestation of Uncommon Etiology

Abiraterone acetate (Zytiga),reduces androgen production by blocking the enzyme CYP 17 and is FDA approved to treat late-stage castrate resistant prostate cancer. Abiraterone causes fluid retention, hypokalemia, and hypertension. Evidence from randomized controlled trials, demonstrate that the incidence of such mineralocorticoid related side effects increase with the duration of medication exposure, rather than the acute dose. We present a patient with metastatic prostate cancer with persistent hypokalemia several days after discontinuing Abiraterone.

A 67 years old male who presented one month after a mechanical fall with a left-upper quadrant fluid collection. Three days after drainage,renal was consulted for evaluation of persistent hypokalemia. Past medical history was significant for Hypertension, Prostate Cancer, Colon Cancer for which he underwent colon resection 10 years prior, Pancreatic Cancer s/p distal pancreatectomy, splenectomy and abdominal wall hernia repair. Initial evaluation revealed Potassium in the range of 1.9-2.9, magnesium was normal. Patient was receiving potassium supplements up to 100meq per day. No history of prior hypokalemia or diarrhea was noted. Physical examination was pertinent for BP of 177/78, Left upper quadrant pigtail catheter and pitting pedal edema. Laboratory data showed: Na:140, K:2.1, Cl:104, Bicarbonate:28, Cr:0.54.Urine studies: Na:47, K:63.6, Cl:140, Cr:64.7, Left Upper quadrant drain, Potassium:5.9. Further review showed that Abiraterone was started 4 months back but patient discontinued medication 1 week prior to presentation. Metabolic work up was initiated and labs were resulted after patient’s discharge. Serum cortisol:22.2(6–23 mcg/dl), 17 OH Progesterone: <10 (<=138 mg/dl),11 deoxy cortisol :10.20 (<=49 ng/dl),ACTH:70 (0-46), Renin: 0.2 (0.2 to 1.6 ng/ml/hr), Serum aldosterone:10 (<= 31 ng/dl), corticosterone:9230(130-820ng/dl). Patient was started on Amiloride 10 mg po daily with normalization of BP and potassium in the next 2 days

Arbiraterone is a potent and selective irreversible inhibitor of CYP17 which is located in the endoplasmic reticulum of the testis, ovaries, adrenals, and placenta. CYP17 catalyzes two sequential reactions-conversion of pregnenolone and progesterone to their 17alpha-hydroxy derivatives by 17 -hydroxylase activity and the subsequent formation of dehydro epiandrosterone and androstenedione, respectively, by C17, 20 lyase activity. Thus, Arbiraterone mimics 17 alpha hydroxylase deficiency, leading to mineralocorticoid excess over time. Diagnosis is confirmed by markedly elevated levels of 11-deoxycorticosterone and corticosterone. Aldosterone and plasma renin concentrations are usually low. In our patient, corticosterone levels were markedly elevated confirming the diagnosis.The fluid retention, hypokalemia, and lower extremity edema due to aribiraterone can be reversed with either or . Nevertheless, spironolactone may function as an agonist for mutated androgen receptors in prostatic tissue and is not recommended. Clinical studies have successfully employed eplerenone with no evidence of loss of tumor control. In this case, we initiated amiloride to manage hypokalemia without interfering metabolic work up. Patient will be switched to epleronone on further follow up visits. James Jackson, MD Category: Clinical Vignette

A Diet of Diet Coke: An Unusual Presentation of Hemolytic Anemia

Introduction: Vitamin B12 deficiency is a frequently investigated cause of megaloblastic anemia. Etiologies include pernicious anemia, medications, H. Pylori infection, prior gastrectomy, and dietary deficiency. While the most common presentation is a macrocytic anemia, profound deficiency can lead to more significant manifestations in some patients.

Case: An 83 year-old female with a prior history of dementia presented to the Emergency Department after her neighbor noted worsening confusion, weakness, and decreased appetite for the past week. It was reported that the patient had recently been treated at a psychiatric facility for psychosis and worsening dementia. The patient herself denied any complaints at time of presentation. Review of systems was notable for decreased PO intake over the past several months and a diet of mostly soda and crackers. On physical exam the patient was oriented to person, but not location, time, or situation. She had an otherwise normal exam with no other significant findings. Laboratory studies demonstrated pancytopenia with a WBC count of 1.1, hematocrit of 14 and platelets of 30 which decreased to 9 several hours later. MCV was significantly elevated at 127. Indirect bilirubin and LDH were both elevated and haptoglobin was below the detectable assay limit. Peripheral smear demonstrated 1-2 schistocytes per HPF. A CT head was obtained that demonstrated a small intraparenchymal hemorrhage. An ADAMTS13 level was mildly decreased at 53. Iron levels were normal accompanied by a mildly elevated ferritin and decreased folate. Vitamin B12 was significantly decreased at 93 pg/ml. The patient was admitted and transfused with packed RBCs, platelets, and FFP for her anemia and thrombocytopenia in the setting of intracranial hemorrhage. After the patient’'s laboratory evaluation returned with evidence of profound B12 deficiency, she was started on intramuscular B12 supplementation at 100mcg/day for 7 days with significant improvement of all of her cell lines and complete resolution of her thrombocytopenia. Her mental status improved daily. The patient was then discharged on continued supplementation with B12, folate, and thiamine and scheduled outpatient hematology follow up.

Discussion: The classic presentation of Vitamin B12 deficiency is a macrocytic anemia that can be accompanied by evidence of demyelinating neurologic dysfunction such as neuropathy, ataxia, and mental status changes. More rarely in cases of profound B12 deficiency, intramedullary and peripheral hemolysis can occur with a significant decrease in all cell lines and a pattern of lab abnormalities similar to that seen in the microangiopathic hemolytic anemias. It is crucial in these cases to quickly recognize a reversible B12 deficiency as severe pancytopenia can present with life threatening manifestations. In our case, the patient presented with profound thrombocytopenia and an intraparenchymal hemorrhage followed by resolution of her hematopoetic abnormalities with adequate B12 supplementation. Diaa Osman, MD Category: Clinical Vignette

Why can't I Stop Bleeding?

Introduction Acquired adult onset amegakaryocytic thrombocytopenia is an extremely rare platelet disorder with only a limited number of cases reported in the literature. Progressively, it has become a recognized phenomenon with various treatment protocols developed to minimize its morbidity and mortality. Below is a rare presentation of this extremely rare disorder and its successful outcome.

Case: 52 year old female presented with persistent and progressive problems with epistaxis, lacrimal bleeding, and gum bleeding. She also endorses easy bruising. A bone marrow aspirate was conducted and findings were consistent with amegakaryocytic thrombocytopenia. She was initially treated with Rituxan, Nplate and cyclosporine with maintenance on Rituxan for twenty months but symptoms relapsed with findings of thrombocytopenia and worsening bleeding episodes. Treatment was reinitiated with Nplate Rituxan, cyclosporine and prednisone with no response. The patient became platelet transfusion dependent and developed steroid induced diabetes and steroid-induced hyperlipidemia. Physical exam: Vital signs/General appearance: Temperature 36.3, heart rate 86, respirations 20, blood pressure 146/85, oxygen saturation 98% on room air, height 154 centimeters, weight 56 kg. Well appearing female patient who was in no distress. No major physical findings including the absence of scleral icterus, healthy within normal findings of cardiac, respiratory, gastrointestinal, hematological or lymphatic, and neurological findings. Skin was absent of any rashes, hives or petechiae. Labs: CBC shows a white blood cell count of 9.4, hemoglobin 13.2, platelets 8. Chemistries are remarkable for glucose of 652. LFT’s are remarkable for an alkaline phosphatase 192. LDH 539. She was subsequently arranged to be admitted to the hospital for a 4 day course of anti-thymocyte globulin of a dose of 40mg/kg along with cyclosporine 12mg/kg and prednisone taper over 2 weeks. The patient’s platelet count was noted to increase and symptoms went in remission, with no repeat bleeding episodes. Further follow-up will define the level of success of this treatment protocol.

Discussion: Amegakaryocytic thrombocytopenia represents extremely rare heterogeneous group of disorders with a varied response to immunosuppression. More commonly seen in its congenital form, the acquired adult onset form typically requires immunosuppressive agents, including anti-thymocyte globulin (ATG) for steroid refractory disease. Early recognition of this diagnosis is key in improving prognosis and limiting symptoms that in some extreme cases can be life threatening. In the case of symptomatic patients, who continue to be refractory to treatment, an appropriate sibling donor, early hematopoietic progenitor cell transplant, even before administration of ATG, may be indicated. David Agyapong, MD Category: Clinical Vignette

Cocained-Induced Vasculitis

An increasing number of cases of cocaine-induced vasculitis are being found among cocaine users in the United States. It is estimated that about 70% of the cocaine used here is contaminated with Levamisole.

We describe a 65 year old male, with a 20 year history of cocaine abuse, who presented with a 1 month history of a progressively worsening, non-healing and painful rash on his trunk and extremities. He denied fever, weight loss and myalgias but admitted to itchiness. Examination showed multiple tender, erythematous and violaceous plaques with central necrosis on the trunk and extremities. These plaques were found to be in different stages of healing with their size ranging from 1cm-7 cms. Lab investigations revealed an elevated creatinine of 2.9, an elevated ESR, a low C3, presence of Myeloperoxidase (MPO) antibody and perinuclear Anti Neutrophil Cytoplasmic Antibody (p ANCA), and an absence of Antinuclear Antibody (ANA) and Anti Proteinase 3 (PR3) antibody. Urine drug screen was positive for cocaine and urine microscopy showed dysmorphic RBCs. Skin biopsy showed thrombotic vasculopathy with overlying re- epithelialazation. biopsy revealed focal endocapillary proliferative glomerulonephritis with crescents in 1 of 10 glomeruli and interstitial fibrosis and tubular atrophy involving approximately 70% of the specimen. This particular case corroborates our findings that cocaine adulterated with levamisole causes vasculitis in some reported cases. Yara Abdou, MD Category: Clinical Vignette

Striking the Right Cord

The skin is an organ that is frequently involved in connective tissue disorders and autoimmune diseases. Patients present with broad-ranging cutaneous manifestations that often aid in directing the differential diagnosis and revealing underlying pathophysiology of the disease. It is essential for internists to appreciate such dermatologic findings in order to strike the right cord and make the right diagnosis.

A 41-year-old female with history of SLE, Raynaud’s phenomenon and Rheumatoid Factor negative arthritis, presented with a chief complaint of joint pain and what she called as “ropes” on her trunk. On exam; vital signs were within normal limits. Skin exam revealed findings of new hyperpigmented, asymptomatic, symmetrical cutaneous cords on her bilateral flanks, extending from the axilla to her hips. The remainder of the exam was unremarkable. Lab tests showed a positive ANA with a titer of 1:2560 and speckled ANA pattern. Anti-dsDNA was positive at 13 with an Anti-RNP positive at 207. Anti Smith antibodies were positive at 45. SSA, SSB and SCL-70 were negative. C3, C4 were normal. Rheumatoid factor was negative at <7. Anti -CCP was negative at 12.8. ESR elevated at 58, CRP elevated at 19.8. Cutaneous biopsy of the involved region revealed superficial and deep perivascular and interstitial dermatitis with a “bottom heavy” inflammatory infiltrate along the junction of the dermis and subcutaneous adipose. Patient was diagnosed with Interstitial Granulomatous Disease (IGD) based on histopathology and clinical correlation. She failed her initial therapyof hydroxychoroquine and methotrexate. No specific treatment was given for her cutaneous lesions, but she was switched to belimumab infusion for her overall connective tissue manifestations with marked improvement.

Interstitial granulomatous disease (IGD) is a rare skin condition, more often seen in middle aged women, that is commonly associated with connective tissue disorders such as rheumatoid arthritis, systemic lupus erythematosus, systemic vasculitis, lymphoproliferative disorders, or autoimmune diseases such as vitiligo, thyroiditis, and diabetes. Ackerman syndrome is used to describe IGD that is associated with non-rheumatoid arthritis. This is a rare disorder, first described in 1993, characterized by the combination of arthritis and the pathognomonic rash (linear cutaneous cords) known as the ‘rope sign’. IGD can have variable clinical manifestations, including symmetric papules, plaques, nodules and, as in our case, linear cords on the lateral aspects of the trunk. This condition should be considered when patients present with typical dermatologic features, such as the rope sign and arthritis. Such patients should always be screened for underlying rheumatic and autoimmune diseases. James Bennett, MD Category: Clinical Vignette

Free Falling in the ICU

Thrombotic Thrombocytopenic Purpura (TTP) is a rare condition known to have various underlying causes. This disease process can result in neurological and renal dysfunction, and will lead to death in 90% of cases if left unrecognized and untreated.

A 26 year old woman with a history of TTP was transferred to the ICU from an outside facility with signs concerning for relapsed TTP. Her initial diagnosis was made 5 years earlier during her first pregnancy. At that time, she was found to have a depressed level of ADAMTS13 of less than 5% in addition to elevated inhibitor of ADAMTS13. She was treated with plasmaphereis and high-dose steroids, eventually requiring Rituximab to achieve remission. On this presentation the patient noted a recent acute onset of headache, dizziness, sore throat and dark urine for which she sought evaluation by her primary care physician. Her exam was notable for tachycardia, icteric sclerae, petachiae of the neck and thigh, and purpura across her upper extremeties. She endorsed a history consistent with a viral prodrome several days before the onset of symptoms. Labs revelaed a hemoglobin count of 8.2mg/dl, platelets of 7, an elevated reticulocyte percentage of at 17%, and schistocytes on peripheral smear. Bilurubin was 3.9 and her pregnancy test was negative. Blood and urin cultures as well as a chest x-ray were normal. A Coombs test was negative and her ADAMTS13 level was deficient. She was started on oral prenisone and fresh frozen plasma. Plasmapheresis was initiated the following day and after clinical improvement she was transferred to the general medicine team. Three days after admission her platelets improved to 47. By hospital day 7 her hemoglobin stabilized and she had platelets of 279. She was discharged with a taper of prednisone to follow up in outpatient clinic.

TTP is a rare disorder involving dysregulation of the clotting cascade that results in hemolysis of erythrocytes, and can lead to renal failure and neurological damage. The key manifestation of the disease is thrombocytopenia with microangiopathic ADAMTS13 protease. In this case, recognition by the patient’s primary care physician was critical to her survival. She responded very well to steroids and plasmapheresis, thus reinforcing the concept of early recognition leading to rapid treatment of a deadlly condition. Lauren Eberly, MD Category: Clinical Vignette

Hyperhemolysis Without Hemoglobinopathy—An Unusual Presentation

Introduction: Hyperhemolysis is characterized by a hemolytic transfusion reaction leading to a life-threatening anemia with a drop in hemoglobin and hematocrit (H&H) to levels markedly lower than were present before transfusion. This is a rare occurrence in patients without hemoglobinopathies. Case reports are usually associated with sickle cell anemia or thalessemia. This case highlights hyperhemolysis secondary to a delayed blood transfusion reaction.

Case Report: 55 year old male with PMH of hypertension and hyperlipidemia sustained multiple fractures after a complex motorcycle accident. He received 10 units of blood for active bleeding during orthopedic surgery. H/H at time of discharge was 8.2/24. Seven days later after discharge, he returned to the ED with progressive dyspnea, nausea and non-bloody emesis. H&H on presentation was 4.6 and 12 a Hgb drop of 56%, WBC at 64.2K, LDH at 2355, total bilirubin at 5.9, indirect at 4.3, and haptoglobin <8, urinalysis positive for hemoglobin. Delayed hemolytic transfusion reaction was confirmed with positive DAT (IgG and complement) and, with Jka antibody isolated as the cause. He became severely symptomatic with H&H at 5.4 and 15, and was transfused with 2 units of Jka negative blood. His H&H initially rose to 6.1 and 16, but sharply dropped to 5.0 and 14. The next day, the H&H had dropped further to 4.6 and 13, and he was transfused again with 1 unit. Again, his H&H rose directly after transfusion to 5.8 and 17, but dropped to 5.4 and 15. He received another unit with subsequent H&H values of 5.3 and 15. Further transfusions were held. Active bleeding was ruled out with negative guaiac, non- significant nasogastric tube findings, and normal abdominal CT. Further workup ruled out glucose-6-phosphate dehydrogenase or pyruvate kinase deficiency, or any underlying hemoglobinopathy. H&H was 6.1 and 19, with a normal WBC at time of discharge.

Discussion: Limited cases reports demonstrate hyperhemolysis with myelofibrosis and anemia of chronic disease, suggesting that hyperhemolysis can occur in the absence of underlying hemoglobinopathies. Our patient developed a delayed hemolytic transfusion reaction, and his hemoglobin and hematocrit dropped to levels lower than pretransfusion with subsequent transfusions, consistent with hyperhemolysis. This case further demonstrates the possibility of hyperhemolysis in patients without hematologic disease; diagnosis of this syndrome should not be dismissed in such patients without a hemoglobinopathy. Navneet Sidhu, MD Category: Clinical Vignette

Glucarpidase in Methotrexate Toxicity: Is it Worth $100,000?

Methotrexate since its invention 1948 has been most widely used anti-cancer agent, and is an important component in the treatment of a variety cancers including leukemias, lymphomas and osteosarcomas. Despite use of leucovorin and alkalization rescue the mortality secondary to renal dysfunction of high dose methotrexate is estimated to be to be 4.4 %.

We present to you a 78 year old male with past medical history of stage IIE large B cell lymphoma of his left testis s/p orchiectomy who was recently initiated on RCHOP treatment regimen for lymphoma. He was admitted for high dose methotrexate administration and his methotrexate level 24 hours after administration was found to be markedly elevated at 15.94(normal being <0.05). Additionally we noted worsening creatinine clearance. Supportive care measures were maximized that included administering additional leucovorin, maintaining urine pH ≥7, and aggressive hydration. Even with maximized supportive measures we were unsuccessful in clearing Methotrexate resulting in subsequent bone marrow and liver toxicity in the form of leukopenia and hepatocellular dysfunction. Given the renal dysfunction and signs of methotrexate toxicity, Glucarpidase was administered to assist with elimination of MTx .Subsequently 24 hours after giving glucarpidase the patients the patients methotrexate level started down trending t0 0.86 and eventually normalized along with the renal function.

Methotrexate toxicity can be fatal and can lead to myelosuppression, mucositis, hepatitis, and dermatitis. Critical determinants of MTX cytotoxicity are not only drug concentration but also duration of exposure. More than 90% of MTX is cleared by the kidneys. And elevated MTX levels cause renal dysfunction which is believed to be mediated by the precipitation of MTX and its metabolites in the renal tubules. Renal dysfunction results in sustained elevated plasma MTX concentrations. Glucarpidase is a noncompetitive enzyme which provides an alternative non renal route of methotrexate elimination by converting methotrexate to its inactive metabolites. Weidman et all concluded that early intervention with the combination of leucovorin and glucarpidase is highly effective in patients who develop HDMTX-induced renal dysfunction. Estimated cost is $100, 000 for a single dose per an article published in annals of pharmacology. FDA-approved use of glucarpidase is in the setting of delayed methotrexate clearance, specifically with elevated sMTX >1 µmol/L and impaired renal function. Given high cost, it is essential to note the patient population who would benefit from the use of this drug. This case demonstrates the importance of monitoring Methotrexate levels, prompt recognition of toxicity, an understanding of the aggressive supportive measures to improve Methotrexate clearance, and the effectiveness of an uncommonly utilized medication, Glucarpidase. Diego Colom Steele, MD Category: Clinical Vignette

Clostridium Difficile - True to its Name

Clostridium difficile infection is a common occurrence following exposure to an antibiotic. However, the correct diagnosis may be difficult to find, even with the availability of sensitive tests.

A 50 year old man visited his regular clinic doctor because of watery diarrhea, an episode of hematochezia and lightheadedness. The patient had a history of aztreonam administration and hospitalization 5 months prior but lived at his home. A clinical diagnosis of infectious gastroenteritis was made and the patient was admitted for IV fluid therapy because of severe volume depletion. The patient had a flexible sigmoidoscopy performed the following day, showing pseudomembranous colitis. A stool sample tested negative for C. difficile toxin A gene via RT-PCR on admission. Standard stool cultures ordered on admission were also negative for common bacterial pathogens. Biopsies from the sigmoid colon were reported as inconclusive as to whether the etiology was C. difficile infection or ischemic colitis. The patient began to complain of abdominal pain, bloating and worsening diarrhea, and was empirically treated with oral metronidazole. A KUB revealed no toxic megacolon. Further testing for C. difficile infection was sent, including GDH antigen and toxin A/B assay, and these were again reported as negative.

The sensitivity of RT-PCR is estimated to be 92%, while the sensitivity of GDH antigen testing ranges from 83 to 93%, while toxin A/B immunoassay sensitivity ranges from 91-93%. The gold standard of diagnosis, however, is either cell culture cytotoxicity assay or toxigenic culture, which are not readily available. CT angiography of the abdomen failed to reveal any evidence of occlusion of mesenteric vessels. At this point, rarer causes of pseudomembranous colitis including Klebsiella oxytoca or Shigella sp. infection, and lymphoma were being considered. However, on the 9th day of oral metronidazole therapy, the patient began to improve considerably. Correspondingly, marked improvement was seen on sigmoidoscopy. A presumptive diagnosis of C. difficile infection was made on the basis of his clinical response. This case illustrates the difficulty in the diagnosis of this common hospital condition, and the limitations of laboratory tests for C. difficile infection. Although the sensitivity and specificity of the laboratory tests used to diagnose C. difficile infection are high, they are by no means absolute. Mary Seiler, MD Category: Clinical Vignette

Mycoplasma Pneumonia: A Novel Risk Factor for Thromboemboli?

Pulmonary emboli are potentially life-threatening events frequently considered in patients with pulmonary complaints. The diagnosis is more likely to be missed when another obvious pulmonary pathology can explain the same complaints.

A 54 year old male without any significant past medical history presented to the emergency department with one week of malaise, nonproductive cough and two days of dyspnea. At presentation he endorsed pleuritic chest pain and headaches. He had smoked half a pack per day until the week prior. He was afebrile, slightly tachycardic and profoundly hypoxic requiring 15 liters on a nonrebreather. His physical exam was unremarkable, and chest xray showed a left lower lobe infiltrate consistent with a bronchial pneumonia vs aspiration. Labs showed a mild leukocytosis. He was admitted and started on community acquired pneumonia treatment with ceftriaxone and azithromycin, with the addition of tamiflu, since he had not received a flu shot that year. On hospital day 4 he had not had significant improvement and infectious labs including flu PCR were negative, so he underwent a noncontrasted CT scan which showed extensive inflammatory bronchiolitis that favored a viral or atypical pneumonia. Due to persistent hypoxia, he underwent CT-chest angiogram on hospital day 7 which revealed multiple segmental pulmonary emboli in his right lower lobe. He had been on prophylactic anticoagulation since hospital admission. Several days later his mycoplasma IgG and IgM both came back positive. A literature review revealed that mycoplasma pneumonia has been linked to pulmonary emboli in several children. Given that his basic malignant work-up was negative, mycoplasma pneumonia was considered his thrombogenic risk factor. Since he was already being treated with azithromycin a high dose prednisone taper was added per Pulmonary recommendations. He required a total of 16 days in the hospital primarily because of his high oxygen requirement. On discharge he was still requiring 4 L of oxygen. He was discharged on coumadin, a lovenox bridge and prednisone.

This case is particularly important because we frequently use the risk stratification model to determine whether a patient should undergo work-up for pulmonary emboli and one question in that model is whether another diagnosis can better explain the patient’s symptoms. In this case the patient did not have any risk factors for pulmonary emboli and had evidence of infection, which could explain his symptoms. An additional consideration is whether mycoplasma bronchiolitis in particular, and any inflammatory process in general, may cause a hypercoagulable state raising the possibility of pulmonary emboli. While risk stratification is an important clinical tool, clinical judgment must be used to recognize when a patient is not responding as expected to clinical treatments thus prompting reconsideration of the initial diagnosis. jairon johnson, MD Category: Clinical Vignette

Subarachnoid Hemorrhage Rarely Reported Manifestation of Granulomatosis With Polyangitiis

Subarachnoid hemorrhage has been rarely reported as a manifestation of granulomatosis with polyangitiis (GPA). We present a case where subarachnoid hemorrhage was the initial presentation of a vasculitis flare.

This is a 42 year old female with a past medical history of GPA, renal failure, renal transplant, hypertension, and hypothyroidism who was admitted to the NICU with a subarachnoid hemorrhage and hypertensive crisis. She had a history of renal failure secondary to GPA with a transplant in 1999. She had a nephrectomy of her transplanted kidney less than 1 month prior to her presentation due to failure of the transplant. Her medication list on admission made no mention of immunosuppression, but on later questioning, she reported that immunosuppression for the transplant was stopped after the nephrectomy. Her hypertension was initially difficult to control with systolic blood pressures in 190’s-200’s. She required multiple medications including a nicardipine drip, clonidine (which she had been on prior to her admission) captopril, hydralazine and amlodpine. Her blood pressure was titrated down to a final goal of below 140 on hydralazine, lisinopril, clonidine, and carvedilol. On the day of transfer out of the NICU she developed papular, erythrematous blanching skin lesions on her forehead. Over the next 2 days the lesions progressed over her face including her forehead, eyebrow and nose, as well as oral ulcers. After development of her skin lesions, several labs were ordered including ANA, ANCA, PR3 and MPO. She was also started on 40mg methylprednisolone and dermatology was consulted and performed a skin biopsy. The biopsies were consistent with GPA. Her methylprednisolone was increased to 100mg every day, and she dramatically improved with resolution of her skin lesions. Her initial presentation of GPA in the past was with renal involvement without significant skin lesions. Her initial presentation during this flare was her subarachnoid hemorrhage with skin manifestations developing later.

Vasculitis is an uncommon cause of subarachnoid hemorrhage. The majority of subarachnoid bleeds are due to aneurysms. There is little data regarding optimal acute management of subarachnoid hemorrhage, and most recommendations focus on hypertension control. This case highlights the importance of considering other causes of subarachnoid hemorrhage as a vasculitis flare requires urgent treatment. It also highlights the importance of questioning patients about past as well as current medications and remembering that immunosuppression for a transplant will also suppress any autoimmune diseases. Benjamin Deaton, MD Category: Research

Trajectory of Patients with MRSA bacteremia

Introduction: MRSA is an important cause of bacteremia and remains the most common pathogen isolated in patients with health care associated bacteremia. It carries a significant mortality and morbidity. The aim of our study is to describe the trajectory and long-term outcomes of patients with MRSA bacteremia and the interplay between bacterial, treatment and host factors. Methods We included all of the patients admitted to the University of New Mexico Hospital between January 1st, 2009 to December 31st, 2013 who were admitted with or developed MRSA bacteremia during their hospital stay. The first episode of bacteremia was considered the index case for each patient. Candidate predictor variables included: host data (age, co-morbidities, McCabe-Jackson score, MRSA carriage status, bacteremia Pitt score and criteria for complicated versus uncomplicated bacteremia), bacterial data (MRSA strain, Panton Valentine Leukocidin production (PVL), presence of Accessory Gene Regulator - AGR) and treatment data (drug and duration). The main outcomes were mortality at 90 days and 1 year. The secondary outcome was hospital readmission during the same period. Predictors were evaluated using survival analysis for outcomes at 90 and 365 days.

Results: We identified a total of 137 distinct patients with MRSA bacteremia. Mean age was 52.3 years ± 16.9, 103(75%) were male, 48(35%) Caucasian and 52(38%) Hispanic. The most common sources of infections were: injection drug use in 40(29%) patients, central venous catheters in 10(7.3%) patients, skin and soft tissue infections in 39(28.5%) patients and pneumonia in 17(12.4%) patients. The MRSA strains were mostly USA100 (44 of 116 patients, 37.6%) and USA300 (67 of 116 petients, 57.3%). PVL production was detected in 28 of 58 (48.3%) isolates and presence of AGR in 13 of 98 (13.3%) isolates. For treatment, 134 (97.8%) received vancomycin, 26(18.9%) received linezolid and 29(21.2%) received daptomycin. The median duration of treatment was 33 days (IQR: 16-42). 21(15.2%) patients died during the index hospitalization. Mortality at 3 months was 21.2% (25 of 118 patients) and 33.3% (33 of 99 patients) at one year. 39 patients were readmitted between 3 months and 1 year, 14(10.3%) for infections, 4(2.9%) with cardiovascular disease, 4(2.9%) with musculoskeletal complications. 14(12.6%) of 111 patients were nursing home residents at 3 months and 5(5.1%) of 98 at one year. Besides the McCabe-Jackson score (HR: 2.7 – 8.3), the only significant predictor of mortality at 3 months and 1 year was the duration of antibiotic treatment HR 0.9(95% CI:0.8-0.9) and HR 0.96(0.9-0.97).

Conclusion: Prehospital comorbidities and duration of treatment are the main determinants of mortality at 3 months and 1 year in patients with MRSA bacteremia. Husam Bader, MD Category: Research

Simple Community Acquired Pneumonia: The Potentially Deadly Missed Detail

Introduction: Community acquired pneumonia (CAP ) is the single most common cause for admissions to the hospital through the emergency department, with nearly one million hospital admissions per year**. This abstract focuses on a vital part of the management that is commonly missed.

Case: A 67 year old woman, with a past medical history of lupus, initially hospitalized with CAP at an outside hospital, improved clinically, was then discharged after three days with oral antibiotics. The patient presented three months later to UNMH with extreme fatigue, non- resolving shortness of breath and new yellowing of the sclera. Initial workup showed a hilar lung mass of 6 x 3.1 cm, with multiple masses in the liver and spine, raising suspicion for metastatic malignant disease. Liver biopsy was obtained which showed poorly differentiated small cell lung cancer. Unfortunately, no cancer treatment was initiated as the patient had progressive liver failure due to metastatic disease burden, and she passed away shortly afterwards.

Discussion: This abstract details a case where a primary lung cancer was missed due to lack of follow up after hospitalization for CAP. This illustrates the need to adhere to the latest guidelines published by ACP advising follow up chest x-ray seven to twelve weeks after treatment for CAP in smokers or patients older than forty to document resolution and rule out a malignant process. 49 cases admitted for pneumonia at UNMH in the past 90 days were reviewed, 22 of them specifically mentioned the need for a follow up with a chest x-ray after discharge. However, 39 mentioned the need to follow up with primary care provider. The latest guidelines published by ACP advise follow up chest x-ray seven to twelve weeks after treatment for CAP in smokers or patients older than forty to document resolution and rule out a malignant process. As this case demonstrates, failure to adhere to these guidelines can have devastating consequences such as a missed diagnosis of primary lung cancer. Clearly a critical aspect of treating CAP involves proper discharge recommendations, which prompted an investigation of recent UNMH admissions for pneumonia in the last 90 days and the discharge recommendations for the purpose of quality improvement. A convenience sample of 49 cases was reviewed, although 39 mentioned the need to follow up with a primary care provider, only 22 of them specifically mentioned the need for follow up chest x-ray after discharge. Thus, not only does this abstract report a case of a missed cancer diagnosis because of a missed chest x- ray, it also highlights the potential need for improvement of discharge recommendations following hospital admissions for pneumonia.

**Published statistics by HealthCare Cost and utilization project / 2006 Lisa Ereifej, MD Category: Clinical Vignette

Mid Back Pain, A Diagnosis in Evolution

Back pain is a common presenting complaint. When a patient presents with back pain one must maintain a broad differential diagnosis to include the most common diagnoses in addition to “do- not-miss” diagnoses. A clinician must maintain a low threshold for imaging when red flags are present.

An 18-year-old woman with no past medical history except for uterine artery embolization at the age of 14 secondary to vaginal bleeding presented with acute onset severe middle back pain of 3 days duration. The pain had persisted which was cause of concern for the patient and hence she sought evaluation. Physical exam was normal with no dysmorphic features except for a slight cleft to her uvula. Eye exam was normal. CBC and chemistry results were normal. CT chest was obtained which indicated a Type B aortic dissection that extended inferiorly, terminating proximal to the renal arteries and appeared to extend into the origin of the superior mesenteric artery. Transthoracic Echocardiogram was normal. There was no indication for surgery, the patient was monitored on telemetry, and was then discharged after blood pressure was controlled with oral antihypertensive medications. Two months later patient was readmitted to the hospital with shoulder and back pain. A repeat CT thorax showed continued increase in the caliber of the descending aortic false lumen and was concerning for left subclavian artery involvement. The patient was transferred to a specialized center for surgical repair. Weeks later genetic testing confirmed a variant in the SMAD3 gene, consistent with Loeys-Dietz syndrome.

Loeys-Dietz syndrome (LDS) an autosomal dominant connective tissue disorder. It was first described in 2005. It is characterized by arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. LDS patients are defined as those with mutations in transforming growth factor B receptor I and II. Deletions encompassing the SMAD3 gene are sufficient to cause features of LDS. Rapidly progressive aortic aneurysmal disease is a distinct feature of LDS. As more individuals are diagnosed with LDS our knowledge of the range of medical features and management principles will continue to evolve. This case illustrates the importance of maintaining a broad differential diagnosis with complaints of severe back pain. LDS has less phenotypical features compared to other more common connective tissues diseases which may result in premature closure in the diagnosis of back pain, and potentially missing the diagnosis of aortic dissection in young patients. This case also illustrates the importance of pursuing an underlying cause of aortic dissection in a patient without classical risk factors for the disease.