Category Archives: Ambulatory Report

Cox’s Conference: Recurrent hypokalemia – Liddle Syndrome

In today’s Cox’s Conference, Dr. Jan Ramesh with expert discussant Dr. Biff Palmer presented a case of recurrent hypokalemia in the setting of lifelong hypertension that ultimately was diagnosed as Liddle Syndrome.

Continue reading Cox’s Conference: Recurrent hypokalemia – Liddle Syndrome

Cox’s Conference: Antiphospholipid Antibody Syndrome

At today’s Cox’s Conference, Dr. Josephine Harrington with expert discussant Dr. Srikanth Nagalla of antiphospholipid antibody syndrome.

Pearls:

-Antiphospholipid antibody syndrome should be suspected in a patient with unprovoked venous and arterial thromboses, especially in a young patient without provocation. Testing can also be considered in women with histories of pregnancy loss, intrauterine growth restriction, preeclampsia, and abruption in settings in which antiphospholipid syndrome is suspected (testing should be limited to lupus anticoagulant, anticardiolipin Ab, and beta 2 glycoprotein Ab)

-Diagnosis is based on clinical criteria of thromboses or pregnancy morbidity in the presence of antiphospholipid antibodies. The antiphospholipid antibodies used in the Sapporo classification are anticardiolipin (IgG and IgM), anti-beta2-glycoprotein (IgG or IgM), and lupus anticoagulant. Repeat confirmatory laboratory testing of the above antiphospholipid antibodies should be confirmed >= 12 weeks apart

-Remember that you need clinical features and laboratory features to diagnosis antiphospholipid antibody syndrome. Thus, there is no value in testing asymptomatic patients

-Multiple positive antiphospholipid antibodies, particularly triple positive (anticardiolipin, anti beta2 glycoprotein, and lupus anticoagulant) are at higher risk of thrombosis

Q: What is the importance of diagnosing antiphospholipid antibody syndrome, particularly in men, who will not have the pregnancy related complications?

A: Antiphospholipid antibody syndrome, due to its high risk of recurrence, typically requires indefinite anticoagulation. This is in contrast to unprovoked or provoked venous thromboses, for which discontinuation can be entertained. However, patient risk factors for bleeding, patient preference, and antibody positivity (e.g. triple positive vs single positive) should be taken into consideration. Moreover, the diagnosis of antiphospholipid antibody syndrome has implications on choice of anticoagulation. The evidence for the use of direct acting anticoagulants is scant, partially due to the rarity of disease limiting feasibility of large scale trials. The RAPS trial demonstrated non-inferiority of rivaroxaban when compared to warfarin; however, surrogate markers of thrombogenicity were used and long-term studies examining the actual thrombosis event rate of rivaroxaban vs warfarin are lacking. Thus, there is a general bias towards vitamin K antagonists in the treatment of antiphospholipid antibody syndrome. Additionally, the knowledge that antiphospholipid syndrome is driving thrombosis may yield additional treatment considerations for recurrent thrombosis while therapeutic on vitamin K antagonists. Hydroxycholroquine has been suggested to decrease the risk of thrombotic events and may be considered as add-on therapy to anticoagulation in such patients.

Q: Can anticoagulation be discontinued based on falling titers of antiphospholipid antibody titers later in life?

A: This is a great question whose answer is waiting to be discovered.

Cox’s Conference: Chronic Urticaria, Penicillin Allergy, and Allergy Pearls

During this week’s Cox’s Conference, we had a special presentation from two of our Allergy/Immunology fellows, Dr. Daniel Har and Dr. Shyam Joshi, with expert discussant Dr. David Khan. They presented had two cases, one of chronic urticaria and another of pneumonia in the setting of reported penicillin and cephalosporin allergy.

Chronic Urticaria:

  • Definition: urticaria that has been continuously or intermittently present for at least six weeks
  • Pathophysiology: unknown. Possibly secondary to auto-allergy mediated IgE activation of mast cells
  • History: blanching wheals that last less than 24 hours, are not painful or burning. Triggers of wheals include pressure, heat, water.
  • Physical Exam:
    • Chronic urticaria
    • Dermatographism
      Dermatographism
  • Testing:
    • Choosing Wisely:Don’t routinely do diagnostic testing in patients with chronic urticaria.In the overwhelming majority of patients with chronic urticaria, a definite etiology is not identified. Limited laboratory testing may be warranted to exclude underlying causes. Targeted laboratory testing based on clinical suspicion is appropriate. Routine extensive testing is neither cost effective nor associated with improved clinical outcomes. Skin or serum-specific IgE testing for inhalants or foods is not indicated, unless there is a clear history implicating an allergen as a provoking or perpetuating factor for urticaria.
    • Skin Biopsy: neutrophils and eosinophils, but NOT leukocytoclasis or fibrinoid necrosis (vasculitis)
  • Differential Diagnosis:
    • Urticaric vasculitis: these lesions are nonblanching, spanning several days and often followed by residual hyperpigmented changes. Biopsy shows leukocytoclasis or fibrinoid necrosis (vasculitis)
  • Management:
    • CU management
      Note: After Step 3, steps 4 through 7 are interchangeable and depends on the experience and preference of provider. Omalizumab has shown remarkable success for remission in several patients

Antibiotic/Drug Allergy Pearls:

  • History of Penicillin Allergy

    • What do you do?
      • Confirm reaction. Oftentimes, these reactions are misdiagnosed, mislabeled, or have waning allergy. 10% of the population endorse a history of penicillin allergy; of these patients, 90% not allergic to penicillins and are able to take these antibiotics safely. If the reaction is not consistent with a mast-cell mediated reaction, the allergy is likely not real.
      • Penicillin Skin Testing:
        • Can be done as an inpatient and outpatient
        • Excellent negative predictive value for excluding penicillin allergy
        • Two-step process: First, PRE-PEN test (benzylpenicilloyl polylysine) and PCN-G test. Then, if negative, amoxicillin 500 mg challenge.
        • Note: Penicillin is the only antibiotic for which there is validated skin testing outcomes. Other skin tests exist but lack rigor in validation
    • What if you want to use a cephalosporin?
      • Medical Myth: 10% of patients with penicillin allergy have a cephalosporin allergy. This was perpetuated by early in vitro studies as well as studies using cephalosporins contaminated with penicillin
      • Facts:
        • The cross-allergy with 2nd, 3rd, and 4th generation cephalosporins in patients with penicillin allergy is negligible. 
        • The cross-allergy with 1st generation cephalosporins is approximately 1%.
  •  Drug Allergies:

    • If you want to determine if a drug is safe to administer in a patient with a reported allergy but has a low pre-test probability actual allergy, refer for a graded challenge.
      • This is purely diagnostic. It does not change tolerance to drug
      • Involves successive exposure to increasingly less dilute doses of the drug in question. The interval between exposures depends on the type of reported reaction

Other High-Value Allergy Pearls:

  • Choosing Wisely:  Don’t perform food IgE testing without a history consistent with potential IgE-mediated food allergy.
    • Testing individuals without a consistent history yields a high rate of false-positive or clinically irrelevant results that waste healthcare resources and lead to unwarranted patient lifestyle restrictions and anxiety.
    • Reactions that are IgE mediated are rapid (minutes to two hours), unless mediated by alpha-gal allergy in meats, with symptoms that can involve the skin, gastrointestinal tract, or cardiovascular system.

 

  • Diagnosis of anaphylaxisdiagnosis of anaphylaxis

 

  • Choosing Wisely:  Don’t diagnose or manage asthma without spirometry.

 

  • Choosing Wisely: Don’t routinely order low- or iso-osmolar radiocontrast media or pretreat with corticosteroids and antihistamines for patients with a history of seafood allergy, who require radiocontrast media.
    • The risk of allergic reaction to IV contrast to patients with shellfish allergy is similar to that of patients who have any form of atopy

Cox’s Conference: Cardiac Stress Testing

In this week’s Cox’s Conference, Dr. Justin Grodin discussed a case presented by Dr. Christopher Puleo in which a 45 year old woman with non-ischemic cardiomyopathy presented with symptoms of worsening dyspnea on exertion and typical angina. During the case, we learned many pearls about the uses, indications, and limitations of cardiac stress testing. Below are selected pearls from our discussion.  Continue reading Cox’s Conference: Cardiac Stress Testing

Cox’s Conference: Adult-Onset Still’s Disease and Leukocytoclastic Vasculitis

Today’s Cox’s Conference is brought to you by expert discussant Dr. Arturo Dominguez who invited two dermatology residents to present us two interesting dermatology cases of adult-onset Still’s disease and of leukocytoclastic vasculitis in the setting of IgA-dominant post-infectious glomerulonephritis.  Continue reading Cox’s Conference: Adult-Onset Still’s Disease and Leukocytoclastic Vasculitis

Cox’s Conference: Immune Thrombocytopenia

Today’s ambulatory report is brought to us by one of our fantastic R3’s, Dr. Ijeoma Oguike, with expert discussant, Dr. Srikanth Nagalla.

Case:

A young man with a history of hypothyroidism presented to clinic with bilateral lower extremity non-blanching petechiae. He otherwise was without any complaints. On exam, he was well appearing and without evidence of hemarthroses or hematomas. He was found to have a platelet count of less than 5,000 thousand per microliter of blood with an otherwise normal CBC. He was negative for HIV and HCV. He was diagnosed with primary immune thrombocytopenia.

Discussion:

Immune thrombocytopenia is an acquired autoimmune condition caused by auto-antibodies (IgG) to one of several possible surface receptors (commonly, the GIIb/IIIa receptor) on platelets. It is a diagnosis of exclusion characterized by isolated thrombocytopenia without another obvious cause. Patients often present without any symptoms but may have signs of primary hemostatic disorders (mucocutaneous bleeding).

Diagnostic Pearls:

-The differential diagnosis for an isolated platelet count in the single digits include: immune thrombocytopenia, drug-induced thrombocytopenia and post-transfusion purpura

-When immune thrombocytopenia is suspected, be sure to test for HIV and hepatitis C as several cases are linked with infection with these agents. Additional testing for other disease states can be considered in select patients with signs and symptoms of disease (e.g. ANA for connective tissue disease).

-Approximately 20% of patients with an initial diagnosis of primary immune thrombocytopenia eventually are diagnosed with secondary immune thrombocytopenia due to other underlying conditions such as autoimmune disease, CVID, lymphoma, HIV, HCV, autoimmune lymphoproliferative syndrome

Treatment Pearls:
Treatment Options

Steroids: prednisone 1 mg/kg with a prolonged taper or dexamethasone 40 mg PO daily for 4 days (mean onset of response is 2-5 days with peak effect 10-14 days)

IVIG: mean onset of response is 1 day with peak effect in approximately 5-7 days

Rituximab: mean onset of response 8 weeks

Splenectomy: mean onset of response varies from immediate to weeks

Thrombopoetin mimetics: If above steps fail, eltrombopag or romiplostim can be used with the goal of stimulation of the bone marrow to generate platelets faster than they can be destroyed. mean onset of response is 2 weeks

Treatment goals:

Note that treatment is not aimed at normalizing platelet counts. Rather, treatment attempts to achieve a goal platelet count of >50000 per microliter of blood to avoid serious bleeding

Q and A:

Q: Why do patients with immune thrombocytopenia have less bleeding relative to their platelet counts?

A: Hemostatic presentations can vary in immune thrombocytopenia. This variability is likely due to the functional effect of the autoantibody on the platelets. Some antibodies are activate platelet aggregation whereas others neutralize. Thus, some patients may tend to bleed while others will have relatively low rates of bleeding relative to their platelet count.

Q: Can plasmapheresis be used for immune thrombocytopenia?

A: Plasmapheresis is most effective for IgM mediated processes. Due to its large size, most IgM molecules are intravascular and can be removed by plasmapheresis. IgG, however, has a large volume of distribution. As such, plasmapheresis is not as effective in immune thrombocytopenia.