Dr. Allison Lange Publishes!

R3 Dr. Allison Lange published a case report today in BMJ Case Reports. She took care of a patient with a history of dermatomyositis who presented to the hospital with fevers and arm pain. The patient was found to have CMV viremia which then precipitated HLH/macrophage activation syndrome. This case report represents the first such report of CMV viremia causing MAS in a patient with dematomyositis.

Dr. Lange wrote this report with Dr. Kazi (our program director), Dr Chen (of hematopathology), and Dr. Barnes (infectious diseases). Great work!

The paper can be found here:

http://casereports.bmj.com/content/2018/bcr-2018-225231.short?g=w_casereports_current_tab

Cox’s Conference: Post-Pericardiotomy Syndrome

In this week’s Ambulatory Cox’s Conference, Dr. Neela Thangada presented a case of a female with history of hypertension, type 2 diabetes, and adrenal insufficiency secondary to pigmented nodular adrenocortical disease who presented with a chief complaint of shortness of breath, one week in duration. Our expert discussant, Dr. Ian Neeland guided us through the differential diagnosis for acute, progressive shortness of breath.

The young female patient was also experiencing orthopnea, paroxysmal nocturnal dyspnea, and exercise intolerance, all symptoms concerning for heart failure. Exam was pertinent for jugular venous distention, muffled heart sounds, and diffuse crackles. Our differential for acute onset of heart failure included myocarditis, myocardial infarction, valvular disease (acute aortic insufficiency), cardiac tamponade, constrictive pericarditis, infiltrative cardiomyopathies, familial cardiomyopathies, endocrinopathies (hyperthyroidism, hypothyroidism, adrenal insufficiency, and acromegaly), and nutritional deficiencies leading to heart failure. A bedside echocardiogram was performed that revealed a pericardial effusion. The patient had a notable history of recent sternotomy for anterior mediastinal mass resection, which made post-pericardiotomy syndrome the likely diagnosis.

Post-Pericardiotomy Syndrome Pearls:

  • Post-cardiac injury syndrome is pericarditis with or without a pericardial effusion as a result of injury to the pericardium.
  • Commonly occurs post-myocardial infarction, known as Dressler Syndrome.
  • However patients can also develop a similar syndrome after cardiac surgery, thoracic surgery that disturbs the pericardium, cardiovascular interventions (percutaneous coronary intervention, pacemaker lead insertion, and radiofrequency ablation), or trauma.1

Clinical Presentation:

  • Occurs after injury to or invasion of the pericardium or myocardium.
  • Typically there is a latent period, weeks to months, between the injury and the development of pericarditis or pericardial effusion.
  • Symptoms include pleuritic chest pain, fever, but heart failure symptoms can occur in the setting of pericardial effusion. Pericardial tamponade is rare (~ 2%).2

Diagnosis:

  • Suspected based on clinical picture (fever, chest pain, shortness of breath) in the setting of recent myocardial infarction or pericardial injury.
  • Laboratory abnormalities include leukocytosis and elevated erythrocyte sedimentation rate and C-reactive protein.2
  • EKG can have diffuse ST-segment elevation and PR depression.
  • Echocardiogram can reveal pericardial effusion.

Treatment:

  • First-line treatment consists of NSAIDs (if there are no contraindications) and colchicine.
  • In cases of refractory disease, systemic glucocorticoids (prednisone at 0.25 – 0.50 mg/kg/day) can be used.3
  • Colchicine may also be effective in prevention of post-pericardiotomy syndrome after cardiac surgery.4

References:

  1. Wessman DE, Stafford CM. The postcardiac injury syndrome: case report and review of the literature. South Med J 2006; 99:309.
  2. Imazio M, Brucato A, Rovere ME, et al. Contemporary features, risk factors, and prognosis of the post-pericardiotomy syndrome. Am J Cardiol 2011; 108:1183.
  3. Adler Y, Charron P, Imazio M, et al. 2015 ESC Guidelines for the diagnosis and management of pericardial diseases: The Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC)Endorsed by: The European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2015; 36:2921.
  4. Finkelstein Y, Shemesh J, Mahlab K, et al. Colchicine for the prevention of postpericardiotomy syndrome. Herz 2002; 27:791.

VA Morning Report- The Pulseless Disease

Yesterday, R3 Dr. Brandon Jakubowski presented a case he initially saw in PRIME clinic – a young lady who presented with a papular rash on her chin. The rash was initially treated conservatively, however progressed and involved painful pustular lesions on the patient’s arms. The patient was seen by dermatology and underwent a biopsy, however ended up going to the emergency room prior to the pathology resulting. In the ER, the patient was hypotensive and was noted to have absent upper extremity pulses. A CT scan was performed and aided in diagnosing Takayasu’s arteritis.

 

For research purposes, the American College of Rheumatology developed diagnostic criteria for Takayasu Arteritis in 1990. Patients must meet at least three of the following six criteria:

  • Age of onset ≤ 40 years old
  • Claudication of extremities
  • Decreased brachial artery pulse
  • Blood Pressure difference > 10mmHg between arms
  • Bruit over subclavian arteries or aorta
  • Arteriogram abnormality (narrowing or occlusion of the entire aorta, its primary branches or large arteries in the proximal upper or lower extremities, not due to arteriosclerosis, fibromuscular dysplasia or similar causes; changes usually focal or segmental)

The modified Ishikawa diagnostic criteria is slightly more complicated but has a higher sensitivity and specificity (92.5% and 95%, respectively) than the original ACR criteria and is notable for removing the age criteria.

In the management of Takayasu Arteritis, immunosuppressants are the cornerstone of therapy, however optimal management is undefined. This particular patient received high dose steroids, then transitioned to tocilizumab when side effects were no longer manageable. It is important to understand that laboratory findings do not reliably track disease activity and therapy is essentially guided by patient symptoms.

 

Further reading:

Arend WP, Michel BA, Bloch DA , et al. The American College of Rheumatology 1990 criteria for the classification of Takayasu arteritis. Arthritis Rheum 1990;33:112934.doi:10.1002/art.1780330811

Kim ESH, Beckman J. Takayasu arteritis: challenges in diagnosis and management. Heart. 2018 Apr;104(7):558-565. doi: 10.1136/heartjnl-2016-310848. Epub 2017 Nov 25.

 

 

Cox’s Conference – Sweet’s Syndrome

In last week’s Ambulatory Cox’s Conference, Dr. Stephen Philip presented a case of a female with history of rheumatoid arthritis who presented with a chief complaint of fever and rash. Initial laboratory studies unveiled an active urinary sediment concerning for glomerulonephritis. Our expert discussant, Dr. Biff Palmer guided us through the differential diagnosis for fever and rash with renal involvement.

In a patient who presents with fevers and rash, the differential diagnosis is broad and includes infectious, autoimmune, neoplastic, and drug-related etiologies. Our patient had evidence of renal involvement with an active urinary sediment concerning for glomerulonephritis. Our differential diagnosis in this patient included systemic lupus erythematosus, vasculitis (IgA vasculitis, ANCA-associated vasculitis, or cryoglobulinemia), common viral illnesses (EBV, CMV, and HIV), infective endocarditis, disseminated fungal infection, and cutaneous malignancy. The patient underwent a skin biopsy which confirmed the diagnosis of Sweet’s Syndrome.

Sweet’s Syndrome Pearls:

·     Also known as acute febrile neutrophilic dermatosis

·     Characterized by abrupt onset of painful, erythematous papules, plaques, or nodules which is frequently accompanied by fever and leukocytosis.

·     Neutrophilic infiltration to other organ systems can very rarely occur, including ocular, musculoskeletal, central nervous system, cardiovascular system, pulmonary system, gastrointestinal tract/liver, and kidneys. Renal involvement, as in our patient, is rare but commonly presents with proteinuria, less commonly with hematuria or renal insufficiency.1-2

·     Most commonly associated with infections (after URI or GI infection), inflammatory bowel disease, pregnancy, autoimmune diseases (RA, SLE, dermatomyositis, sarcoid), malignancies (more commonly hematologic malignancies), and drug related (most common is G-CSF).

Clinical Presentation:

·     Patients will have abrupt onset of painful inflammatory papules, plaques, or nodules. The distribution will be asymmetric with the upper extremities most commonly effected.

·     Often associated with fever, arthralgias, headache, myalgias, and malaise.

·     Extracutaneous involvement can occur, frequently ocular and musculoskeletal. However additional organ systems can also become involved.

·     Laboratory studies often show a peripheral leukocytosis with neutrophilia. An elevated erythrocyte sedimentation rate and C-reactive protein is common, along with anemia and platelet abnormalities.

Diagnosis:

·     Diagnostic criteria has been established – both major criteria is required along with two of four minor required.3

o     Major Criteria:

§     Abrupt onset of painful erythematous plaques or nodules

§     Histopathologic evidence of a dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis

o     Minor Criteria:

§     Fever, > 38 C

§     Association with underlying maligiancy, inflammatory disease, or pregnancy OR preceded by URI, GI infection, or vaccination

§     Excellent response to treatment with systemic glucocorticoids or potassium iodine

§     Abnormal laboratory values at presentation (need 3 of the 4: ESR > 20 mm/hr, positive C-reactive protein, > 8,000 leukocytes, > 70% neutrophils).

Treatment:

·     Corticosteroid therapy is first-line. Typically start with prednisone at 0.5 to 1mg/kg per day.

·     After initiation of steroid therapy, symptoms are expected to improve within 48 hours.

·     Once disease control is obtained, can begin to taper steroids with a plan to discontinue steroids within 4-6 weeks.

·     Other therapies such as colchicine, dapsone, and potassium iodide have been used as steroid-sparing agents.4

References:

1.     Cohen PR, Kurzrock R. Sweet’s syndrome revisited: a review of disease concepts. Int J Dermatol 2003; 42:761-778.

2.     Vignon-Pennanmen MD. The extracutaneous involvement in the neutrophilic dermatoses. Clin Dermatol 2000;18:339–47.

3.     von den Driesch P. Sweet’s syndrome (acute febrile neutrophilic dermatosis). J Am Acad Dermatol 1994; 31:535.

4.     Cohen PR, Kurzrock R. Sweet’s syndrome: a review of current treatment options. Am J Clin Dermatol 2002; 3:117.

NEJM Res 360 Journal Club: Hosted by UTSW Internal Medicine Residency

UTSW has been chosen to work with NEJM hosting a journal club. We will be reviewing the paper “Procalcitonin-Guided Use of Antibiotics for Lower Respiratory Tract Infection” (ProACT). The Journal has recruited three of the study authors to help us provide some insight into the design and execution of the trial.

Please visit here for the discussion: https://resident360.nejm.org/discussions/679

Anybody can access the discussion and contribute!

 

The paper can be accessed here: https://www.nejm.org/doi/full/10.1056/NEJMoa1802670

VA QI Morning Report – PICC?

This morning at the VA we did a mini M&M based on this case regarding the appropriateness of PICC lines in a patient with CKD/ESRD with diabetes and osteomyelitis.

PICCs should generally be avoided in patients with an eGFR <45 ml/min/1.73m2 or placed only after consultation with a nephrologist. The reason for this is PICC placement can harm future candidacy for AV fistula placement, the safest and most effective method of hemodialysis.

There are alternatives for patients needing long-term IV access that may preserve the central and peripheral vasculature in the event HD is needed. The MAGIC criteria have helped to delineate the most appropriate intravenous catheter for your patient. The original paper, published in 2015, can be found here. The authors have also developed an app, which can be found here.

 

https://psnet.ahrq.gov/webmm/case/450/dont-pick-the-picc

http://annals.org/aim/fullarticle/2436759/michigan-appropriateness-guide-intravenous-catheters-magic-results-from-multispecialty-panel

http://www.improvepicc.com/magic-app.html

 

Parkland Morning Report 7/18 – Lupus Cerebritis

At today’s morning report at Parkland R2 Corbin Eule presented a case of a 68 year-old female with 2 weeks of confusion and lower extremity motor and sensory neuropathy, on a background of chronic fatigue, malaise and unintentional weight loss.

Our case discussion was led by pulmonary/ critical care faculty Dr Carlos Girod. The initial differential was broad and included malignancy with paraneoplastic syndrome, connective tissue disorders, and infiltrative disorders such as amyloidosis and sarcoidosis. The patient’s admission labs were notable for pancytopenia and normal renal function and urine sediment. An autoimmune panel was revealing with ANA >1:2560, positive anti-dsDNA antibodies, and low complement levels. Subsequent studies included a bone marrow biopsy showing LE cells and peripheral nerve biopsy consistent with vasculitis.

The patient was diagnosed with systemic lupus erythematosus (SLE) and received a course of “pulse” dose methylprednisolone followed by initiation of mycophenolate and an oral prednisone taper, with which she clinically improved.

SLE Pearls:

–     SLE may present with a wide variety of neuropsychiatric manifestations, including cognitive dysfunction, encephalopathy, polyneuropathy, psychosis, mood disorders, and coma1.

–     Neuropathy associated with SLE is thought to be due to vasculopathy of the small arteries supplying nerves; given the systemic nature of the disease, multiple nerves can be affected at once2.

–     LE cells were first described in 1948 by hematologists Dr Malcolm Hargraves and Dr Robert Morton, who found cells in the bone marrow of patients with SLE that appeared to have had their nuclei phagocytosed by mature polymorphonuclear cells3.

Clinical Presentation:

–     SLE is diagnosed by likelihood (definite, probable or possible SLE) using clinical and immunologic criteria such as that described by the American College of Rheumatology (ACR)4 or the Systemic Lupus International Collaborating Clinics (SICC)5.

–     The presence of neurologic manifestations in the absence of other known causes is one of the clinical criteria described by both societies, as is the presence of blood cell dyscrasias (hemolytic anemia, thrombocytopenia, leuko- or lympho-penia), and serum autoantibodies (ANA, anti-dsDNA, anti-Sm or antiphospholipid antibodies) that were seen in this case.

Treatment:

–     Treatment of SLE depends on the severity of the flare, with systemic corticosteroids and immunosuppressants forming the mainstay of treatment.

–     Determining dosing intensity and duration of corticosteroid therapy for treatment of SLE is challenging. Whereas historically “pulse” steroids (methylprednisolone 0.5 to 1g/day for 3 days) were commonly regarded as the gold standard for severe SLE flares, more recent evidence suggests that lower doses may be equally efficacious, with reduction in infectious side effects6.

References:

1. The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis and rheumatism. 1999;42(4):599-608.

2. Florica B, Aghdassi E, Su J, Gladman DD, Urowitz MB, Fortin PR. Peripheral neuropathy in patients with systemic lupus erythematosus. Seminars in arthritis and rheumatism. 2011;41(2):203-211.

3. Hepburn AL. The LE cell. Rheumatology (Oxford). 2001;40(7):826-827.

4. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis and rheumatism. 1997;40(9):1725.

5. Petri M, Orbai AM, Alarcon GS, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis and rheumatism. 2012;64(8):2677-2686.

6. Badsha H, Edwards CJ. Intravenous pulses of methylprednisolone for systemic lupus erythematosus. Seminars in arthritis and rheumatism. 2003;32(6):370-377.

Joey Harrington Publishes!

 

R3 Dr. Josephine Harrington published her new review “Should Metformin Remain First-Line Therapy for Patients with Type 2 Diabetes Mellitus and Atherosclerotic Cardiovascular Disease? An Alternative Approach” today in Current Diabetes Reports.

 

Dr. Harrington reviews the evidence for cardiovascular effects of antihyperglycemic agents, proposing the major aim of therapy of type 2 diabetes should be to reduce CV events and deaths. In the face of newly developed diabetes therapies with proven CV safety, is metformin the best option to improve CV outcomes?

 

Dr. Harrington publishes this review with former UTSW IM resident and current UTSW cardiology fellow Natalia de Albuquerque Rocha, UTSW cardiology fellow Kershaw Patel , Dr. Subodh Verma, and UTSW Cardiologist Dr. Darren McGuire. The review can be found here.

Cox’s Conference: Enteric Fever

In last week’s Ambulatory Cox’s Conference, Dr. Roger Fan presented a case of a young female who presented with fevers, rash, and headache. Our expert discussant, Dr. James Luby guided us through the differential diagnosis for the constellation of symptoms – fever, rash, and headache.

In a patient with an acute presentation of fever, rash, and headache the differential diagnosis is broad and includes infectious, autoimmune, and drug-related reactions etiologies. It is important to elicit a thorough history from the patient including travel history, exposures (insects, animals, sick contacts), medications, immunization history, and immune status of the host. The patient had history of recent travel to Nepal to visit family. Our differential diagnosis in this patient included common viral illnesses (EBV, CMV, and HIV), tick-born illnesses (Rocky Mountain spotted fever, Ehrlichiosis/anaplasmosis, and Lyme disease), meningococcal infection, disseminated gonococcal infection, and travel related illnesses (Malaria, Dengue fever, Typhoid/paratyphoid (enteric fever), Zika and Chikungunya). The patient was diagnosed with Salmonella typhi (enteric fever).

 

Enteric Fever Pearls:

  • Classically caused by Salmonella enterica serotype Typhi, however other serotypes including S. enterica Paratyphi A, B, or C can cause a similar syndrome.1
  • Typhoid and enteric fever can be used interchangeably
  • More common in children and young adults
  • Most prevalent in poor areas with overcrowding and poor access to sanitation (south-central Asia, Southeast Asia, and southern Africa have the highest incidence of S. Typhi infection).
  • US has ~ 200-300 cases of S. Typhi per year (80% of these cases are in travels to countries where enteric fever is endemic). 2

Clinical Presentation:

  • Classic presentation includes fever, abdominal pain, constipation/diarrhea, “rose spots” (salmon-colored macules on trunk and abdomen), and headaches. Less common manifestations include cough, arthralgias/myalgias, intestinal perforation, and neurologic manifestations (encephalopathy, acute psychosis, myelitis, and disorded sleep patterns).1
  • Symptoms begin ~ 5-21 days after ingestion of the causative organism (typically through contaminated water or food).
  • Common laboratory derangements include cytopenias – anemia, leukopenia (leukocytosis more common in children), and elevated liver enzymes.

Diagnosis:

  • Must have high clinical suspicion in patients who have traveled to endemic areas.
  • Blood and stool cultures should be obtained. Blood cultures are 40-80% sensitive. Stool studies have a 30-40% sensitivity.1
  • Positive cultures can take several days to incubate, empiric therapy should be started in patients with a high clinical suspicion.
  • Serology testing can be performed, however positive results may represent prior exposure.

Treatment:

  • In patients with severe or complicated disease (organ dysfunction, systemic toxicity, or requires hospitalization), initial therapy with ceftriaxone is appropriate.3
  • In patients with uncomplicated disease who can be treated as an outpatient, fluroquinolone or azithromycin is first line.3
  • Multi-drug resistant strains of S.Typhi are prevalent worldwide. These strains can be commonly resistant to ampicillin, trimethoprim-sulfamethaxazole, and chloramphenicol. Increasing resistance to fluroquinolones is also a growing issue, particularly in South Asia.3

 

References:

  1. Parry CM, Hien TT, Dougan G, et al. Typhoid fever. N Engl J Med 2002; 347:1770.
  2. Lynch MF, Blanton EM, Bulens S, et al. Typhoid fever in the United States, 1999-2006. JAMA 2009; 302:859.
  3. Kariuki S, Gordon MA, Feasey N, Parry CM. Antimicrobial resistance and management of invasive Salmonella disease. Vaccine 2015; 33 Suppl 3:C21.

Metformin and B12 deficiency

Today at VA Morning Report, a question came up about metformin and B12 deficiency and how often to screen for B12 deficiency in patients being treated with metformin. The short answer is that there are no set guidelines. The long answer is:

Metformin has been reported to cause a decrease in serum B12 concentrations. Cross-sectional studies report a wide range of prevalence of biochemical vitamin B12 deficiency with metformin exposure, ranging from 5.8% to as high as 40%. Though the exact mechanism is not known, it is thought to be caused by B12 malabsorption: it is thought that metformin interferes with the calcium-dependent membrane action responsible for vitamin B12-intrinsic factor absorption in the terminal ileum.

A recent report from the Diabetes Prevention Program (DPP) / DPP outcomes study (DPPOS) assessed the risk of B12 deficiency with metformin. The study contained adult participants from 27 centers in the US. Patients treated with metformin 850 mg BID vs placebo. B12 levels were assessed at 5 years (n = 857, n = 858) and 13 years (n = 756, n = 764). Low B12 (≤ 203 pg/mL) occurred more often in the Metformin group than the Placebo group at 5 years (4.3 vs 2.3%; P = .02) but not at 13 years (7.4 vs 5.4%; P = .12). Combined low and borderline-low B12 (≤ 298 pg/mL) was more common in metformin group at 5 years (19.1 vs 9.5%; P < .01) and 13 years (20.3 vs 15.6%; P = .02). Anemia prevalence was higher in metformin group but did not differ by B12 status. The prevalence of neuropathy was higher in the metformin group with low B12 levels. In the patients with biochemical B12 deficiency, homocysteine levels were was elevated consistent with true B12 tissue deficiency.

Several researchers globally have made recommendation to screen those with T2DM on metformin for B12 deficiency. The group above proposed screening for B12 deficiency prior to initiating metformin (>/= 3-4 years), use of high doses of metformin (>/= 2 g/day), clinically worsening diabetic distal polyneuropathy in the presence or absence of anemia. The most recent American Diabetes Association Standards of Medical Care in Diabetes – 2018 makes the following statement: “Long-term use of metformin may be associated with biochemical vitamin B12 deficiency, and periodic measurement of vitamin B12 levels should be considered in metformin-treated patients, especially in those with anemia or peripheral neuropathy.” (Grade B). No formal recommendations have been provided by USPSTF.

Please refer to this article for more information! Vanita R. Aroda et al and the Diabetes Prevention Program Research Group. Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2016 Apr; 101(4): 1754–1761.