Eosinophilic Granulomatosis with Polyangiitis (EGPA) a.k.a Churg-Strauss Syndrome

Introduction

In 1951, Churg and Strauss described a syndrome with a relatively uniform clinical picture of severe asthma, fever, peripheral eosinophilia, and symptoms of “vascular embarrassment” in 13 patients initially diagnosed as having polyarteritis nodosa. Churg-Strauss syndrome (CSS) or Eosinophilic Granulomatosis with Polyangiitis (EGPA) is an uncommon form of antineutrophil cytoplasmic antibody-associated necrotizing vasculitis affecting the small-to-medium sized blood vessels. Disease typically follows three phases.

Etiology

  • Although the etiology of this disease is not well known, both T- and B-cell mediated immunity have been considered.
  • Hyper-responsiveness to antigenic stimuli may be the etiologic factor in the development of CSS.
  • In 1998, Wechsler and colleagues reported eight patients with this syndrome after a decrease or withdrawal of oral steroids.
  • Also cases have been attributed to antibiotics such as erythromycin, azithromycin and roxithomycin and some metered dose inhalers (bamuterol, salmeterol and nedrocromil)

Clinical Manifestations

  • The prodromal phase presents as adult-onset asthma, atopic disease, and allergic rhinosinusitis. It precedes the vasculitic phase by 3 to 9 years but intervals as long as 30 years have also been described.
  • Next, is the eosinophilic phase which is usually a subclinical eosinophilic tissue infiltration without necrosis but can sometimes manifest as pulmonary infiltrates or nodules with or without pneumonitis, or as gastroenteritis.
  • The third and final phase is the vasculitic phase, where patients are usually diagnosed. The mean age at presentation varies from 38 to 52 years of age, but can range from 7 to 74.
  • The most common manifestations at the time of diagnosis were asthma (91.1%), weight loss (49.3%), mononeuritis multiplex (46%), sinusitis or polyposis (41.8%), skin lesions (39.7%), and lung infiltrates (38.6%).

Diagnosis

  • Laboratory Studies
    • Eosinophilia usually appears in the second phase of disease, but can also initially present in the prodromal or vasculitic phases.
    • The presence of ANCA is documented in approximately 40% of EGPA and appears to be associated with renal and upper respiratory tract involvement, alveolar hemorrhage, purpura, biopsy-proven vasculitis and peripheral neuropathy.
      • The absence of ANCA is associated with pulmonary disease, cardiomyopathy, and fever.
      • The origin of this dichotomy is uncertain but it is hypothesized that the tissue damage in ANCA-negative EGPA is directly related to the presence of tissue eosinophils, whereas the ANCA-positive patients are thought to have endothelial damage in the typical ANCA-associated vasculitis fashion.
  • Criteria
    • In 1990, the American College of Rheumatology established the classification criteria for EGPA with a sensitivity of 85% and specificity of 99.7%.
    • Fulfillment of 4 or more criteria is needed for classification as EGPA.
      1. Asthma
      2. Eosinophilia greater than 10% on differential white blood cell count
      3. Mononeuropathy or polyneuropathy
      4. Migratory or transient pulmonary infiltrates detected radiographically
      5. Paranasal sinus abnormality
      6. Biopsy with perivascular eosinophils.
  • Imaging
    • The most common radiological findings are lobular or centrilobular peripheral consolidation and nodularity, thickened bronchial walls, inter-lobular septum, and peri-cardial and pleural effusion.
    • On computed tomography, enlargement of or distortion of peripheral pulmonary arteries may be seen.
  • Pathology
    • Histological diagnosis is by demonstration of vasculitis that is necrotizing, tissue infiltration with eosinophils and extra-vascular granulomas are found in a few cases

Differential Diagnosis

  • The differential diagnosis includes polyarteritits nodosa, Wegener’s granulomatosis, drug reaction, bronchogenic granulomatosis, fungal and parasitic infections, and malignancy

Treatment

  • Regularly with prednisone starting at 40-60 mg a day
  • Cyclophosphamide or azathioprine can be added with the purpose to limit the disease or spare steroids.
  • In case of fulminant disease or multi-organ involvement, parenteral corticosteroid such as methylprednisolone is used.
  • If response to mentioned treatment is not seen, parenteral immunoglobulin is administered.
  • Newly experimental medications for unresponsive cases are mycophenolate mofetil and tumor necrosis factor (TNF)-α blockers (such as etanercept and infliximab).
  • Treatment is continued at least one month after remission

Modified from:

– BMC Musculoskeletal Disorders 2014, 15:388

– Journal of Medical Case Reports 2010, 4:188

Answer to CC #8

Case Challenge #8 presented a 42 year old female with fever, rash, and worsening shortness of breath.  She started to exhibit symptoms after starting a leukotriene inhibitor and tapering off steroids. Exam revealed fever, mild hypoxia, and prominent bilateral wheezing. She also had palpable purpura on both of her legs. Neurologic exam reveals foot drop on the right. Labs revealed a peripheral eosinophilia and elevated inflammatory markers. Imaging revealed bilateral peripheral infiltrates.

We asked which of the following is most likely to be helpful in the diagnosis of this case?

The results of the voting are as follows:

Untitled

The correct answer is: P-ANCA!

The patient has Eosinophilic Granulmomatosis with Polyangiitis (EGPA, formerly known as Churg-Strauss Syndrome)
  • Small vessel vasculitis associated with allergies, asthma, pulmonary disease and eosinophilia
  • Can also involve skin, heart, kidneys, GI tract and nervous system (mononeuritis multiplex)
  • Dx: granulomatous vasculitis on Bx, eosinophils; p-ANCA positivity
  • Often flares with steroid tapering or with leukotriene receptor antagonists

Thanks for playing, case challenge #9 will be posted next Tuesday!

Resident Update Talk: Type 1 Diabetes

Dr. Jeremy Warshauer, future endocrinologist, gave us a great RUT this week on Type 1 Diabetes. He reviewed the pathophysiology, epidemiology as well novel and upcoming treatment options including the Bionic Pancreas and Pancreatic Islet Cell Transplantation. Take at look!

(A note to email subscribers: The powerpoint is only visible from the full site. Click on the link above to be taken directly to the site)

“Remember when we tested for porphyria by…”

This week at Weissler Conference we talked about how acute porphyria used to be diagnosed many years ago – exposing urine to ultraviolet radiation (the sun!) and the color becoming purple-pink. This was even mentioned in the TV show, Scrubs, when JD accidentally diagnoses a patient with acute porphyria by this method in the episode “My Dumb Luck” (thanks to Punag for the reference). The diagnosis is now established in a patient who presents with neurovisceral symptoms (abdominal pain, nausea, vomiting, constipation, neuropathies) with a substantial elevation in urinary porphobilinogen.  Measurements of fecal, serum, urine porphyrins and and erythrocyte porphobilinogen deaminase (PBGD) will help distinguish the type of acute porphyria. Check out the review article below from Blood to learn more about porphyrias!

The porphyrias: advances in diagnosis and treatment.

(image courtesy of http://scrubs.wikia.com/wiki/My_Dumb_Luck)

DO I NEED VITAMIN D?!

Dr Holick, endocrinologist and mineral metabolism specialist from Boston University, gave us a rousing Grand Rounds about vitamin D deficiency. The recommendations for vitamin D supplementation, which Dr. Holick notes afflicts almost everyone, are below:

 


However, these dosing recommendations change for patients with obesity, as increased body weight can increase the need for vitamin D up to 2-3 fold. Dr. Holick’s research is prolific, so take a look at a recent article about the need for increased vitamin D dosing in obese patients.


The Importance of Body Weight for the Dose Response Relationship of Oral Vitamin D Supplementation and Serum 25-Hydroxyvitamin D in Healthy Volunteers

Unlike vitamin D recommendations by the Institute of Medicine, the Clinical Practice Guidelines by the Endocrine Society acknowledge body weight differentials and recommend obese subjects be given two to three times more vitamin D to satisfy their body’s vitamin D requirement. However, the Endocrine Society also acknowledges that there are no good studies that clearly justify this. In this study we examined the combined effect of vitamin D supplementation and body weight on serum 25-hydroxyvitamin (25(OH)D) and serum calcium in healthy volunteers. We analyzed 22,214 recordings of vitamin D supplement use and serum 25(OH)D from 17,614 healthy adult volunteers participating in a preventive health program. This program encourages the use of vitamin D supplementation and monitors its use and serum 25(OH)D and serum calcium levels. Participants reported vitamin D supplementation ranging from 0 to 55,000 IU per day and had serum 25(OH)D levels ranging from 10.1 to 394 nmol/L. The dose response relationship between vitamin D supplementation and serum 25(OH)D followed an exponential curve. On average, serum 25(OH)D increased by 12.0 nmol/L per 1,000 IU in the supplementation interval of 0 to 1,000 IU per day and by 1.1 nmol/L per 1,000 IU in the supplementation interval of 15,000 to 20,000 IU per day. BMI, relative to absolute body weight, was found to be the better determinant of 25(OH)D. Relative to normal weight subjects, obese and overweight participants had serum 25(OH)D that were on average 19.8 nmol/L and 8.0 nmol/L lower, respectively (P<0.001). We did not observe any increase in the risk for hypercalcemia with increasing vitamin D supplementation. We recommend vitamin D supplementation be 2 to 3 times higher for obese subjects and 1.5 times higher for overweight subjects relative to normal weight subjects. This observational study provides body weight specific recommendations to achieve 25(OH)D targets.