EUH Morning Report: Review of Still’s Disease

The Bottom Line: Still’s disease, more specifically adult-onset Still’s disease (AOSD) is  a diagnosis of exclusion. Various infectious, neoplastic, and autoimmune diseases can mimic its clinical manifestations and need to be ruled out for diagnosis (DynaMed Plus, 2018). It is a rare systemic inflammatory disease with 1-34 cases per 1 million people. AOSD is equally distributed among men and women, with peak ages of onset of 15-25 and 36-46 years (Giacomelli et a, 2018).

References: DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 – . Record No. 114565, Adult-onset Still disease; [updated 2018 Aug 24, cited 2018 Sep 5]; [about 13 screens]. Emory login required.

Giacomelli R, Ruscitti P, Shoenfeld Y. A comprehensive review on adult onset Still’s disease. J Autoimmun. 2018 Sep;93:24-36. Doi:10.1016/j.jaut.2018.07.018.

Summary: George Still described 22 children with systemic onset juvenile idiopathic arthritis in 1897. In 1971, Eric Bywaters reported 14 adult patients with symptoms similar to pediatric Still’s disease, such as skin rash, fever, and polyarthritis. Thus, AOSD was defined. It remains a multisystemic disorder of unknown etiology and difficult diagnosis (Giacomelli et al, 2018).

Current AOSD treatment is aimed at targeting pro-inflammatory signs and symptoms, preventing organ damage and life-threatening complications, minimizing adverse effects. Giacomelli et al (2018) confess that recent evidence suggest new insights in AOSD pathogenesis and highlight new therapeutic targets, thus AOSD management may be improving “in the next future.”

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Grady Morning Report: What are the current guidelines concerning the management of acute pulmonary embolism (PE)?

The Bottom Line:

Only one of the phase 3 clinical trials investigating the use of new direct oral anticoagulants in patients with VTE reported efficacy results for the subgroup of patients with acute PE and RV dysfunction. Among patients with elevated NT‐proBNP levels, recurrent VTE occurred in 15 of 454 patients in the edoxaban cohort and in 30 of 484 patients in the warfarin group.

A new trial, the Pulmonary Embolism International Trial (PEITHO‐II) will focus on the safety, efficacy and cost‐effectiveness of dabigatran in the treatment of patients with acute intermediate‐risk PE. Patients will be treated with low molecular weight heparin for at least 72 hours followed by dabigatran treatment for 6 months.

References: Klock FA et al. Management of intermediaterisk pulmonary embolism: uncertainties and challenges. Eur J Haematol. 2015 Dec;95(6):489-97. doi: 10.1111/ejh.12612. Epub 2015 Jul 15.

Link to current trial (still recruiting patients): https://www.escardio.org/Working-groups/Working-Group-on-Pulmonary-Circulation-and-Right-Ventricular-Function/Education/peitho-2

Summary:

Reperfusion Treatment

A. The Pulmonary Embolism Thrombolysis Trial (PEITHO) compared, in a double‐blind manner, fibrinolysis with tenecteplase plus heparin vs. placebo plus heparin in 1005 patients with acute PE. Eligible patients had RV dysfunction, plus myocardial injury; that is, they were at intermediate‐high risk of an adverse early outcome. The primary outcome, a composite of all‐cause death or hemodynamic decompensation/collapse, was significantly reduced with tenecteplase. On the other hand, there was an increased incidence of hemorrhagic stroke after fibrinolytic treatment with tenecteplase; major non‐intracranial bleeding events were also increased in the tenecteplase group compared with placebo. This study strongly argues against the standard application of thrombolysis in hemodynamically stable PE patients.

B. Catheter‐directed techniques are considered an alternative to surgery. The safety and efficacy of pharmacomechanical fibrinolysis is supported by the results of a recent trial which enrolled 150 patients with submassive (intermediate‐risk) or massive (high‐risk) PE. Due to the lack of high‐quality studies in patients with PE in general as well as in patients with intermediate‐risk PE specifically, the safety and efficacy of these interventions remain unknown.

Anticoagulation Treatment

New non‐vitamin K‐dependent oral anticoagulants (NOACs), in particular direct factor IIa (thrombin) and factor Xa inhibitors, were developed and tested in large phase‐3 randomized clinical trials. A meta‐analysis of the phase III clinical trials on VTE showed that new oral anticoagulants were associated with a significantly lower risk of major as well as fatal hemorrhage compared to VKA treatment. The experience with NOACs in current trials on intermediate risk PE is limited.

 

 

EUH Morning Report: Review of type 1 vs type 2 hepatorenal syndrome

The Bottom Line: Hepatorenal syndrome (HRS) is functional renal impairment in patients with advanced liver disease and without evidence of renal parenchymal disease, severe volume loss, or nephrotoxicity from medication.

    • type 1 hepatorenal syndrome
      • rapid decline in renal function
      • doubling of serum creatinine from baseline to > 2.5 mg/dL (221 mcmol/L) in < 2 weeks
      • usually triggered by precipitating event causing both a decline in liver function as well as a decline in other organ functions leading to hepatorenal syndrome
    • type 2 hepatorenal syndrome
      • steady, progressive decline in renal function (average serum creatinine 2 mg/dL [176.8 mcmol/L])
      • usually characterized by refractory ascites and sodium retention

Reference: DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 – . Record No. 116729, Hepatorenal syndrome; [updated 2018 May 30, cited 2018 June 28]; [about 15 screens]. Emory login required.

EUH Morning Report: What is Sister Mary Joseph’s nodule?

The Bottom Line: Sister Mary Joseph’s nodule is a metastatic cancer of the umbilicus that is typically associated with adult cancers of the gastrointestinal tract and ovary (Albano and Kanter, 2005). It is a rare but important physical finding and is a sign of advanced stage of malignancy (Tso et al, 2013).

References: Albano EA, Kanter J. Sister Mary Joseph’s Nodule. N Engl J Med. 5 May 2005;352(18):193.

Tso S, Brockley J, Recica H, Ilchyshyn A. Sister Mary Joseph’s Nodule: an unusual but important characteristic of widespread internal malignancy. Br J Gen Pract. 2013 Oct;63(615):551-552. Doi: 10.3399/bjgp13X673900.

Summary: The condition is named after Sister Mary Joseph (1856-1939), a surgical assistant for Dr. William Mayo, who noted the association between paraumbilical nodules observed during skin preparation for surgery and metastatic intraabdominal cancer confirmed at surgery (Albano and  Kanter, 2005).

EUH Hunt Conference: What is the history of hand, foot, mouth disease in adults?

The Bottom Line: Most commonly diagnosed in children, hand, foot, mouth disease (HFMD) infects approximately 11% of exposed adults, and less than 1% of those infected experience clinical manifestations of the disease (Ramirez-Fort et al, 2014). Most cases resolve on their own, yet supportive treatment can alleviate fever, pain and inflammation (DyanMed Plus, 2018).

References:  DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 – . Record No. 116931, Hand-foot-and-mouth disease; [updated 2018 Feb 22, cited 2018 Jun 19]; [about 10 screens]. Available from http://www.dynamed.com/login.aspx?direct=true&site=DynaMed&id=116931. Emory login required.

Ramirez-Fort MK, Downing C, Hung Q, et al. Coxsackievirus A6 associated hand, foot and mouth disease in adults: Clinical presentation and review of the literature. J Clin Virol. 2014 Aug;60(4):381-6. Doi:10.1016/j.jcv.2014.04.023

Summary: Complications are rare but can include the following (DynaMed Plus, 2018):

  • temporary nail shedding
  • myocarditis
  • pulmonary edema
  • neurologic complications
    • viral oraseptic meningitis
    • brainstem encephalitis
    • neurogenic pulmonary edema
    • acute flaccid paralysis
    • opsoclonus-myoclonus syndrome
    • cerebellar ataxia
    • Guillain-Barre syndrome
    • transverse myelitis

EUH Hunt Conference: A review of Horner syndrome

The Bottom Line: Horner syndrome results from an interruption of sympathetic innervation to the eye. The classic triad is unilateral ptosis (slight narrowing of the ocular fissure), miosis (smaller pupil on the affected side), and anhidrosis (lack of perspiration on the forehead or face). Horner syndrome is not likely to cause any functional visual disturbance but is of great importance clinically as a “red flag” warning that the oculosympathetic pathway has been interrupted and thus there may be potentially life-threatening lesions in the head, neck, and chest.

Reference: Martin TJ. Horner syndrome: a clinical review. ACS Chem Neuroscience. 2018 Feb 21;9(2):177-186. Doi:10.1021/acschemneuro.7b00405

Summary: The first, and perhaps most important, aspect of evaluating suspected Horner syndrome is a careful history. The history often reveals an obvious cause, such as trauma or neck/chest surgery, or will show that the Horner syndrome had been present for many years and therefore may not require an extensive investigation. The history may also reveal other symptoms that would help localize the lesion causing the Horner syndrome. A careful examination is obviously also critical, as other causes of anisocoria or ptosis may need to be considered rather than Horner syndrome, and concomitant signs (for example, a sixth nerve paresis) may help localize a potential lesion. After this, pharmacologic testing can be helpful to confirm diagnosis. Many clinicians will elect not to evaluate Horner syndrome if it has been present for greater than two years.

Though often benign or idiopathic, the cause of Horner syndrome can be very threatening or even lethal, so understanding how to recognize, diagnose, and appropriately evaluate Horner syndrome is important to all clinicians.

EUH Dressler Conference: A review of cardiac sarcoidosis

The Bottom Line: Cardiac sarcoidosis (CS) is the cardiac manifestations of sarcoidosis, a systemic disease of unknown cause characterized by immune granulomas. Cardiac involvement is clinically apparent in 5% of patients with sarcoidosis, but detected in approximately 20% of white and black American persons and 70-80% of Japanese persons at autopsy. The classification of CS is based on disease course:

  • acute sarcoidosis (Lofgren syndrome) resolves spontaneously within 2 years
  • chronic sarcoidosis resolves within ≥ 3-5 years
  • refractory sarcoidosis characterized by progressive disease despite treatment

(DynaMed Plus, 2017)

References: Yatsynovich Y, Dittoe N, Petrov M, Maroz N. Cardiac sarcoidosis: A review of contemporary challenges in diagnosis and treatment. Am J Med Sci. 2018 Feb;355(2):113-125. Doi:10/1016/j.amjms.2017.08.009

DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 – . Record No. 306338, Cardiac sarcoidosis; [updated 2017 Mar 31, cited 2018 Apr 13]; [about 11 screens]. Available from http://www.dynamed.com/login.aspx?direct=true&site=DynaMed&id=306338. Emory login required.

Summary: CS may be asymptomatic and is often presented by sudden death. Most deaths attributed to CS are caused by arrhythmias or conduction system disease, and congestive heart failure may occur. Current consensus on diagnosis relies on endomyocardial biopsy, in the absence of which, histologic proof of extracardiac sarcoid involvement is necessitated. The primary therapeutic approaches are broadly divided into two categories: pharmacological management and invasive or device oriented (Yatsynovich, Dittoe, Petrov, & Maroz, 2018).

 

EUH Krakow Conference: Review of Kikuchi-Fujimoto Disease

Bottom line: “Kikuchi–Fujimoto disease, or Kikuchi’s disease, also known as histiocytic necrotizing lymphadenitis, is a rare, benign, self‐limiting condition characterized by cervical lymphadenopathy and fever….symptoms usually resolve spontaneously within 1–4 months. However, cervical lymphadenopathy can persist for up to 6 months and even 1 year. There is a possibility of recurrence, yet rates of only 3–4% have been reported. The treatment of Kikuchi’s disease is primarily supportive and aims to facilitate the relief of symptoms with the use of analgesics, antipyretics, and rest. In a more severe or protracted disease course, short‐duration oral corticosteroid therapy is the treatment of choice. There are no specific guidelines regarding the dosage or length of treatment. Hydroxychloroquine is another therapeutic option that has been used to achieve rapid clinical improvement in Kikuchi’s disease. The safety profile of hydroxychloroquine may make it a better alternative to long‐term, high‐dose corticosteroids as it has fewer adverse effects. Despite a lack of recommendation, intravenous immunoglobulin, given its immunomodulatory nature, has also been used successfully in patients with severe disease. The mortality rate with Kikuchi’s disease was calculated to be 2.1%. Patients diagnosed with Kikuchi’s disease should be subject to close long‐term monitoring for the possible development of SLE [systemic lupus erythematosus]. Kikuchi’s disease can precede the onset of SLE by years.”1 Review articles provides several histopathological and dermatological images of patients with the condition.

ReferenceMathew LM, Kapila R, Schwartz RA. Kikuchi-Fujimoto disease: a diagnostic dilemmaInt J Dermatol. 2016 Oct;55(10):1069-75. doi: 10.1111/ijd.13314. Epub 2016 May 21. 

EUH Krakow Conference: Review of Lemierre’s Syndrome

Bottom Line: Vijay and Fattah1 state that Lemierre’s syndrome typically presents in young adults who were previously healthy. In a case series of 222 patients who fit the “Lemierre’s syndrome case presentation, the median age was 19 years and 89% of patients were aged 10 to 35 years.”2 Its four key elements are “primary oropharyngeal infection within 4 weeks, suppurative thrombophlebitis of the internal jugular (IJ) vein, metastatic septic emboli, and [a] causal association with F necrophorum.” It should be “suspected in those with a recent history of oropharyngeal infection presenting with fever and rigors, with or without evidence of metastatic lesions, particularly respiratory symptoms (pleuritic chest pain, dyspnoea, haemoptysis).” Penicillin/beta-lactamase inhibitor, penicillin plus metronidazole, and carbapenem” are “appropriate empirical antibiotic regimens….There are no controlled trials to guide management, but most sources recommend between 2–6 weeks of antibiotics in total.” Review article provides four computed tomography pulmonary angiogram (CTPA) images with red arrows that indicate locations of multiple peripheral nodular lesions.

References:

1. Vijay V, Fattah Z. Lesson of the month 1: Lemierre‘s syndrome: a reminder of the ‘forgotten disease.’ Clin Med (Lond). 2018 Feb;18(1):100-102. doi:10.7861/clinmedicine.18-1-100.

2. Riordan T. Human infection with Fusobacterium necrophorum (Necrobacillosis), with a focuson Lemierre’s syndrome. Clin Microbiol Rev. 2007 Oct;20(4):622-59. doi:10.1128/CMR.00011-07.

EUH Morning Report: Review of microscopic colitis

Bottom Line: “Microscopic colitis is a common cause of chronic watery diarrhea, particularly in the elderly. The accompanying symptoms, which include abdominal pain and fatigue, can markedly impair patients’ quality of life. Diagnosis is based upon characteristic histologic findings of the colonic mucosa….Two recent randomized studies have confirmed the effectiveness of oral budesonide for both induction and maintenance treatment of microscopic colitis and is now endorsed by the American Gastroenterological Association as first-line treatment.”

Reference: Cotter TG, Pardi DS. Current approach to the evaluation and management of microscopic colitis. Curr Gastroenterol Rep. 2017 Feb;19(2):8.