All posts by andersodav

Moffitt Pearls – Rheumatology Report – 8.21.2017 – Evan’s Syndrome and SLE

Thank you to Leah for presenting a very interesting case of a young man with history of lupus c/b APS and DVT presenting with thrombocytopenia+ hemolysis found to have Evan’s Syndrome (ITP + AIHA)!

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Key Pearls

  1. Although the term is falling out of favor Evan’s syndrome describes the combo of ITP & AIHA.
  2. For unclear reasons, lupus flares are often accompanied by a dissociation between ESR (high) and CRP (nl or minimal elevation). Other findings of flare (vs. infection) include drop in complement, recued leukocyte count and + RBC casts and/or proteinuria.
  3. Direct oral anticoagulants have not been studied nor are they recommended as anticoagulants in patients with lupus and known DVT. Treat with warfarin or LMWH only!

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More on Evan’s Syndrome

  • Combination of Coombs-positive warm AIHA and immune thrombocytopenia (ITP).
  • Antibodies that cause platelet destruction are unique from those that cause AIHA.
  • Differential Diagnosis:
    • Infectious (eg, HCV, HIV)
    • SLE
    • Lymphoproliferative disorders
    • Common Variable immunodeficiency
  • Treatment (similar to ITP, however azathioprine and cyclophosphamide are used)
    • First line therapy: Glucocorticoid @ 1-2 mg/kg +/- IVIG
    • Second line: Azathioprine or rituximab
    • Third line: Splenectomy
    • Under investigation: Eltrombopag –> a TPO receptor agonist stimulating platelet formation

American College of Rheumatology Classification of SLE

[Always verify all prior diagnoses of rheumatological conditions]

  • SLE Criteria > 3 of 11 ( Se & Sp > 95% and all DO NOT have to be at the same time)
    • Cutaneous Manifestations
      • Malar Rash
      • Photosensitivity
      • Discoid Rash
      • Oral ulcer
    • MSK
      • Nonerosive arthritis – oligioarticualr; symmetrical, migratory
    • Cardiopulmonary
      • Serositis – pleuritic or pericarditis
    • Renal
      • Proteinuria or cellular Casts – > 500 mg/dL on UA or 3+ on dip

 

    • Neurological
      • Seizures OR psychosis

 

    • Hematological
      • Hemolytic anemia or leukopenia, or lymphopenia or thrombocytopenia
    • Serologies
      • +ANA
      • +anti-dsDNA or antiphopholipid Abs

 

Review of Hemolytic Anemias based on Smear

Picture2

Moffitt Pearls 8.16.17 – Endocrine Report – Central AI & Hypothyroidism

Case Summary

Thank you to Emma for presenting a fascinating case of a middle aged man with SCC of the head and neck treated with a PD-1 inhibitor p/w hyponatremia found to have SIADH 2/2 hypothyroidism and central adrenal insufficiency (AI)!!!

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Key Pearls

  1. Remember that replacement of thyroid hormone without replacement of glucocorticoids can precipitate acute adrenal insufficiency.
  2. Nonthyroidal Illness (formerly known as Euthyroid Sick Syndrome) is a normal response to illness and is a relative hypothyroid state marked by elevated TSH and depression of Free T4 and T3.
    • NOTE: Thyroid function should not be assessed in seriously ill patients unless there is a strong suspicion of thyroid dysfunction (thanks Brad Monash!).
  3. A standard stimulation test is 250 mcg of IV Cosyntropin which tests ability of ACTH -> increase cortisol (more details below)

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Evaluation of Adrenal Insufficiency

The HPA Axis

  • A primary adrenal disorder resulting in deficiency of cortisol = 1° AI or Addison’s disease
  • A pituitary disorder resulting in deficiency of corticotropin (ACTH) secretion = 2° AI
  • A hypothalamic disorder resulting in deficiency of corticotropin-releasing hormone (CRH) and secondarily of ACTH = 3° AI

Evaluation of HPA Axis Response to ACTH

  • Early am cortisol < 3 is virtually diagnostic of primary OR secondary AI; >17 rules this out
    • If unclear (often the case) then go to stim testing!
  • Standard Stim test is 250 mcg of IV Cosyntropin
    • Measure cortisol before, 30 & 60 min after intravenous (IV) injection
    • If f/u cortisol is greater than 18, this indicates normal adrenal function
    • A inadequate response suggests EITHER primary or secondary AI
      • Measure ACTH:
        • High = primary AI
        • Low = secondary or tertiary AI

AI

Copyright © 2000-2015 The Cleveland Clinic Foundation. http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/endocrinology/

Moffitt Pearls 8.15.17 – Anaphylaxis and Drug Reactions

Case Summary:

Thank you to Karen for presenting a mystery case of a young man with hx of asthma, seasonal allergies and eczema p/w perioral edema, itching and profound hypotension concerning for anaphylaxis! We discussed the importance of early therapy for anaphylaxis, drug reaction patterns and the possibility of serum sickness in the setting of Bactrim exposure and the atypical nature of her presentation.

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Key Pearls

  1. Anaphylaxis is a Type 1 IgE mediated hypersensitivity reaction that usually occurs within in minutes of an allergen exposure.
    • Volume and IM epinephrine are mainstays of therapy and should NOT be delayed.
  2. Drug reactions are often delayed days to weeks from drug exposure (make sure to review a log) and are mediated by Type IV hypersensitivity.
  3. Angioedema may be manifested by IgE mediated (Type I Hypersensitivity) drug reaction
    • IgE-mediated reactions tend to become more severe & progress toward anaphylaxis (Bactrum as in our case) upon re-exposure to causative agent

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Classification of Allergic Reactions

Type Description Mechanism Clinical Features
I Anaphylactic Usually IgE dependent release of vasoactive substances (histamine, prostaglandins and leukotrienes) Anaphylaxis (definition below), Angioedema, urticarial, GI Sx and bronchospasm
II Antibody (AB)-dependent cytotoxicity Antigen/Haptan associated with cell binds AB -> cell/tissue damage Hemolytic anemia, Interstitial nephritis
III Immune Complex Disease Formation of Antigen-Antibody (AB) Complexes Causes damage Serum Sickness
IV Cell-mediated or Delayed Hypersensitivity Antigen sensitizes T cells, then mediates tissue injury Delayed dermatitis or drug reaction

Drug Reaction Patterns Discussed

SJS (< 10 % body surface area)/TEN (>30% body surface area)

  • Mucosal involvement required, occurs usually within 8 weeks of drug exposure

DRESS

  • Systemic involvement (fever, adenopathy elevated LFTs) driven by eosinophilia; Reaction begins 2-6 weeks after exposure to offending drug

AGEP

  • Reaction often occurs 48-72 hours after drug exposure

Fixed Drug Eruption

  • Usually without mucosal involvement, occurs anytime – days to weeks after drug exposure

Erythroderma

  • >90% of body surface area involved; ddx wide and includes drugs ~ 20% cases and malignancy (Cutaneous T-cell lymphoma)

anap

 

Moffitt Pearls – 8.11.17 – Saddle Nose Deformity, Upper GI Bleeding &Munchausen Syndrome

Thank you to HH and Neil for both presenting today! HH first presented a mini case of a patient who came in for a gout flare that was found to have a saddle nose deformity.

Neil then presented the interesting case of a young woman with a hx of gastric ulcers presented with epigastric pain and hematemesis who after extensive work-up including CT and EGD was found to have Munchausen syndrome!************************************************************************************

Key Pearls

  1. The differential diagnosis for saddle nose deformity falls into the classic triad of infectious, inflammatory and malignancy per table below.
  2. 80% of upper GU bleeds are due to four causes: peptic ulcer disease (35%), esophagogastric varices (30%), esophagitis (10%) and Mallory-Weiss tears (~5%).
  3. The management strategy for a pt. w/ munchausen syndrome is VERY difficult, but should include a single provider (w/ help from psychiatry) and goal to limit interventions + discuss diagnosis with patient in a supportive manner.

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Differential Diagnosis for Saddle Nose Deformities

Infectious Inflammatory Malignancy Other
Syphilis GCA (formerly Wegner’s) NK T-cell Lymphoma Trauma
Leprosy Sarcoidosis Locally invasive tumor (BCC) Cocaine
TB Relapsing polychondritis Lymphomatoid Granulomatosis Surgery
Cutaneous Leishmaniosis      
Septal abscess      

 Differential Diagnosis for Hematemesis AND Fever

  • Mallory-Weiss Tear
  • Peptic ulcer bleeds c/b perforation
  • Hemosuccus pancreaticus (pseudoaneurysm/aneurysm)
  • Upper GI Malignancy – hemobilia, widespread esophageal/gastric malignancy

Munchausen Syndrome or Factitious d/o Imposed on Self

  • Definition: Falsified general medical or psychiatric symptoms
  • Risk Factors: Females, Unmarried, Healthcare professional
  • Diagnostic Criteria (DSM-5):
  1. Falsification of physical or psychological signs or symptoms, or induction of injury or disease, associated with identified deception
  2. The individual presents himself or herself to others as ill, impaired, or injured
  3. The deceptive behavior is evident even in the absence of obvious external rewards
  4. The behavior is not better explained by another mental disorder, such as delusional disorder or another psychotic disorderPrognosis: Very poor even as multiple studies have shown limited benefit even with psychotherapy
  • Management: One provider should oversee pt with help of psychiatry w/ goal to limit interventions. One should be sure to exclude all possible medical conditions and then discuss diagnosis w/ pt in supportive manner

 

Moffitt Pearls 8.8.17 – Undifferentiated systemic Rheumatic Disease & ILD

Thank you, Saate, for getting us started this am with a young man reporting 10 days of cough with complete white out of the left side of his chest found to have a large empyema!

Thank you, Emma and Gabby, for co-presenting the fascinating case of a young woman with history of RA coming in with persistent cough and fever.

**Key Pearls**

Ditty Pearl: Copper deficiency is an uncommon nutritional deficiency seen in patients after gastric bypass and results in a myelopathy localizing to the posterior columns and bilateral corticospinal tracts

Image Pearl: Tracheal deviation towards or away from a dense hemithorax can help distinguish volume loss (atelectasis) from a fluid occupying processes (i.e. lung collapse from massive pleural effusion or hemothorax)

Case Pearl: Rheumatologic diseases most frequently associated with pulmonary involvement, specifically ILD are scleroderma, myositis, dermatomyositis, MCTD and rheumatoid arthritis

Undifferentiated systemic Rheumatic Disease and Overlap Syndromes

  • As many as 25% of rheum disease in patients with systemic symptoms cannot be definitely diagnosed (don’t feel bad Emma and Gabby!)
  • Evaluation of a patient w/ possible autoimmune disease includes the following:

1) How was their disease diagnosed (clinical history and serologies)?

2) What therapies or diagnostic evaluations have they had?

3) What Rheum disease processes fall within their clinical presentation? (Use clinical history to dictate further work-up & serology evaluation)

ILD

 

Moffitt Pearls 7.10.17 – PD-1 Inhibitors & PCP Pneumonia

Pulmonary Report 7.10.17

Thank you to Ugo for presenting the case of an elderly male with widely metastatic melanoma refractory to PD1 inhibitors presenting with 1-2 weeks of fatigue, FTT, DOE found to have PCP pneumonia!

Top Pearls:

  • PD1 inhibitors are considered first-line therapy for metastatic melanoma.
  • Common toxicities of immune check point inhibitors include immune-mediated inflammation of virtually any organ system. See below for more details on PD1 inhibitors.
  • The risk for opportunistic infections w/ checkpoint inhibitors is related to the steroids that are generally given to treat the checkpoint inhibitor toxicities. A case report & paper (https://www.ncbi.nlm.nih.gov/pubmed/27501841) illustrating this risk.
  • Remember! For patients on steroids if > 20 mg/day of prednisone for > 2 weeks –> give PCP prophylaxis. (per expert opinion -> the rule of Dr. Jen B!)

Which patient that are immunocompromised get PCP?

  • HIV-positive patients (CD4 < 200)
  • Cancer, solid organ transplant, BMT – related to type & chemo intensity
  • Rheumatologic (GPA has intrinsic risk)
  • Chronic steroids (see Jen rule above)

Steroids for Rx of PCP in HIV-Negative patients??

  • Not well studied in HIV-negative patients, only a few retrospective studies
  • No mortality benefit, but may expidite recovery
  • Steroids are recommended in the AJT guidelines
  • 40-60 mg Prednisone BID x 5-7 days with 7-14 day taper

 

Table Comparing PCP in HIV Positive and Negative Patients (thanks Jen!)

table PCP

 

PD-1 Inhibitors (blast from the past)

pd1

Emerging data show that 20% of patients with melanoma treated with ipilimumab achieve long-term survival! See this associated review.

PD-1 (programmed cell death 1) and its association with the ligand (PD-L1) is a necessary step in stimulating apoptosis of T-cells, serving as an immune checkpoint. PD-L1 is generally expressed by native cells, signaling to the T-cell “I’m one of you! Don’t hurt me”.  Some tumors have been found to also express PD-L1, enabling them to evade destruction by T-cells.  In order to treat these malignancies, PD-1 inhibitors (pembrolizumab, nivolumab) serve to block the interaction between PD-1 and PD-L1, enabling T-cells to stay “programmed on”, and thus enable immune-mediated destruction of tumor.

Because of this mechanism of action, a common consequence is the upregulation of cell-mediated immunity and, unfortunately, inhibition of native tissues to turn off T-cells. As a result, we commonly see autoimmune-mediated inflammation manifested as new rash, diabetes, thyroid disease, pneumonitis, hepatitis, colitis, etc.

Common Immune-Mediated Toxicities Seen with Check-point Inhibition:

Organ System Manifestation Management
Skin & Mucosa Pruritic rash (most common!)

Alopecia

Vitiligo

Mucositis

Topical corticosteroids

Oral antipruritics

Consider oral steroids

GI Tract Diarrhea/colitis – presents ~6wks into treatment R/O infxn

Anti-motility agents

Steroids if severe

Liver Hepatitis (rate <5%, severe toxicity very rare) Stop therapy if moderate-severe.

Steroids + mycophenolate given rarely.

Lung Pneumonitis – (rate <5%, but occasionally fatal) Steroids common. Infliximab, cyclophosphamide also used, though patients requiring therapy beyond steroids have nearly 100% mortality.
Endocrine Hypophysitis

Autoimmune thyroid disease

Adrenal Insufficiency T1 DM

Hormonal replacement

Steroids

Less commonly reported immune-mediated adverse events include the following: acute renal injury, pancreatitis, neurotoxicity (GBS, myasthenia gravis, PRES, aseptic meningitis, autoimmune encephalitis), cardiotoxicity (myocarditis), hematologic (cytopenias), and ocular inflammation.

Many of the adverse events described above can be managed with continued use of PD-1 inhibitors if mild. However, for severe adverse reactions, PD-1 inhibitors are withheld and potential discontinued permanently.

Moffitt Pearls 7.5.17 – Wilson’s Disease & Hemolytic Anemia

Thank you to Vincent for presenting a challenging case of a young woman with anxiety and depression presenting with unexplained jaundice and cirrhosis, later representing with a severe, hemolytic anemia. Although similar to a prior case presented last month then this was a second presentation of possible Wilson’s disease

 Top Pearls:

  1. Acute alcoholic hepatitis is a chronic disease (despite the name!). Presentation is based on predominantly cumulative burden – a single binge in a patient with otherwise minimal alcohol intake is unlikely to cause severe alcoholic hepatitis.
  2. In a young patient (< 35 yo) with new diagnosis of cirrhosis, consider genetic causes including Wilson’s, hemochromatosis, alpha-1 antitrypsin disease, autoimmune hepatitis, PBC, PSC. Vascular disease and infectious hepatitis should also be considered.
  3. The combination of liver disease and hemolysis raises concern for Wilsonian Crisis, which can herald impending acute liver failure.

Laboratory Diagnosis of Tumor Lysis Syndrome

Alcoholic Hepatitis

The clinical syndrome of acute alcoholic hepatitis includes the following compilation of laboratory and clinical features:

  • Moderately elevated transaminases in a 2:1 ratio of AST/ALT
  • Typically less than 300, rarely greater than 500
  • Elevated bilirubin and Jaundice
  • Jaundice generally develops within 3 months prior to presentation
  • Fever & Neutrophilic Leukocytosis
  • Both should only be ascribed to alcoholic hepatitis after ruling out infection!
  • Right upper quadrant pain – can often palpate tender hepatomegaly
  • Clinical history of chronic drinking with or without recent bing
  • It’s not uncommon that patients have actually decreased their drinking in the weeks-months preceding acute alc hep due to the onset of symptoms with alcohol intake.

See this RCT from NEJM regarding pentoxifylline vs. prednisolone for the treatment of alcoholic hepatitis. Bottom line:  Acute alcoholic hepatitis is a profoundly morbid disease with very high mortality (30-40% in 6 months).  Prednisolone was associated with a reduction in 28-day mortality, but did not reach significance and there were no improvements in 90-day or 1 year mortality.

Autoantibodies Associated with Causes of Cirrhosis

 

Autoimmune hepatitis

IgG, ANA, antismooth muscle Ab, anti-liver-kidney microsome-1 Ab, anti-liver cytosol Ab-1

Primary biliary cirrhosis

ANA, anti-mitochondrial Ab

Primary sclerosing cholangitis

IgM (40-50%), p-ANCA (30-80%)

Wilson Disease (WD) & Hemolytic Anemia

  • Wilson’s disease (WD) is an inherent disease, caused by mutations in the ATP7B gene leading to decreased excretion of copper into the bile
  • Copper accumulation results in injury to the liver and the central nervous system (thank you Muazzum for you amazing neuro ROS)
  • WD presents in a fulminant form with hepatocellular dysfunction, hemolysis and various multiorgan failures (Wilson’s crises)
  • Wilson disease can cause a Coombs-negative hemolytic anemia WITHOUT schistocytes reported in the literature
  • The exact mechanism of the haemolytic process has yet to be defined. copper inhibits sodium potassium ATPase in the erythrocyte leading to haemolysis (and likely without schistocytes as in this case).
  • Medical treatment includes chelating agents and/or zinc, but these have not proved effective in fulminant liver failure, where only liver transplantation (LTx) is regarded as lifesaving.
  • Some limited data for plasmapheresis for rapid copper removal
  • Portends very poor prognosis, often leading to acute liver failure

 (see attached an article on a review of Wilson’s and Hemolytic anemia compliments of HH!!)

Blast from the past!!! Approach to Hemolytic Anemia (thank you Katie!!)

 

 

https://www.evernote.com/shard/s307/sh/16c1d172-fb95-4da7-93b0-d85e5c25854f/3768012329b5e8d8e358cacd312f033a