Q:

12/12/2017
18 year old white male with history of Bell's Palsy at age 16, presented in spring with wheezing and shortness of breath. He was treated for asthma with oral steroids, steroid inhalers and albuterol. He was seen for three more exacerbations in the next three months and received oral steroids each time. In August, he had a rash on his hand associated with the asthma symptoms. A CBC was drawn off oral steroids which revealed a WBC of 27.94 with 78% eosinophils (21.79 kU/L). CXR was normal. Rheumatoid panel negative. I saw him for the first time in October. He was using high dose inhaled steroids, LABA, and albuterol. Repeat CBC with WBC of 11.36 kU/L with 57% eosinophils (6.48 kU/L). His FEV1 62% with 12% reversibility. Subsequent work up included skin testing which showed sensitization to a few molds, and negative or normal CMP, troponin, C-ANCA, P-ANCA, C3, C4, CH50, Aspergillus IgG, B12, strongyloides Ab, Toxocara IgG, Aspergillus IgE, cortisol, UA, FISH Analysis for SCFD2, LNX, PDGFRA, PDGFRB, FGFR1, BCR/ABL1, and negative bone marrow biopsy. Chest CT with a few nonspecific nodules 1-2 mm in size. He continues to have and FEV1 of 60%. Most CBC WBC 9.98 kU/L with 58% eosinophils (5.79 kU/L).

What should be the next step in evaluation? Would the new biological medications be helpful or harmful? Should I send him to CV surgery for a lung biopsy looking for Churg-Strauss? Should we wait and see if hand rash recurs to biopsy? Any imaging that would be helpful?

 

A:

Answer:
From the information provided, your patient has persistent peripheral eosinophilia at sufficient levels to qualify for hypereosinophilic syndrome. His asthma is recent onset and the Bell’s palsy may or may not have been associated with eosinophilia. The differential includes eosinophilic pneumonia, eosinophilic bronchitis, hypereosinophilic syndrome and eosinophilic granulomatosis with polyangiitis (EGPA or Churg Strauss vasculitis). The negative ANCA does not exclude the diagnosis of but the CT scan results would exclude eosinophilic pneumonia. The small nodules would not be particularly helpful in the differential and the small size limits likelihood of value from biopsy. The facial palsy could be a manifestation of EGPA, although it is probably more likely with granulomatosis with polyangiitis (GPA or Wegener’s granulomatosis) [1,2]

My response to your individual questions are:
1. The next step in evaluation would be to initiate a therapeutic trial with anti-IL5 mepolizumab. I favor mepolizumab over the other options because of the 2017 FDA approval for EGPA (3,4,5,6) It would also be helpful to verify that the peripheral blood eosinophil count responds to systemic corticosteroids to be more assured that the eosinophilia is dependent on T lymphocytes and IL-5.
2. I would not request a lung biopsy with the current findings. I would consider a high resolution CT scan of chest without contrast if FEV1 decreased further.
3. I would not delay treatment pending a reoccurrence of the rash.
4. The only imaging I would consider would be a high resolution CT of chest if the prior CT was not a high resolution. However, I would not obtain at this time if lung function remained stable. I would recommend a cardiac ultrasound or consultation with a cardiologist.

In summary, I favor the diagnosis of EGPA because of the persistent asthma with low FEV1, negative ANCA which is more common with EGPA than GPA, absence of renal abnormalities or nodules on chest imaging and the degree of peripheral eosinophilia. The diagnosis of EGPA requires tissue eosinophilia with vasculitis but the safety of anti-IL5 therapy, the potential value for the asthma as well as EGPA would lead me to initiate therapy without tissue biopsy. If your patient developed any additional neurologic changes or evidence of renal disease, I would recommend tissue biopsy as you may need to utilize cytotoxic therapy, such as cyclophosphamide. I would monitor very carefully and repeat laboratory testing to monitor renal function. If eosinophil count does not normalize with anti-IL5 therapy, I would also consider immunosuppressant therapy.

1. Jeong, Sang Mee, et al. "Progressive Bilateral Facial Palsy as a Manifestation of Granulomatosis With Polyangiitis: A Case Report." Annals of rehabilitation medicine 40.4 (2016): 734-740.
2. Greco, Antonio, et al. "Churg–Strauss syndrome." Autoimmunity reviews 14.4 (2015): 341-348.
3. Kim, Sophia, et al. "Mepolizumab as a steroid-sparing treatment option in patients with Churg-Strauss syndrome." Journal of Allergy and Clinical Immunology 125.6 (2010): 1336-1343.
4. Wechsler, Michael E., et al. "Mepolizumab or placebo for eosinophilic granulomatosis with polyangiitis." New England Journal of Medicine 376.20 (2017): 1921-1932.
5. Guillevin, Loïc. "Vasculitis: Mepolizumab for eosinophilic granulomatosis with polyangiitis." Nature Reviews Rheumatology 13.9 (2017): 518-519.
6. https://www.drugs.com/newdrugs/fda-approves-nucala-mepolizumab-eosinophilic-granulomatosis-polyangiitis-churg-strauss-syndrome-4657.html

I hope this information is of help to you and your patient.

All my best.
Dennis K. Ledford, MD, FAAAAI

 

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