Hypereosinophilic syndrome (HES) is a heterogeneous group of rare disorders associated with persistent eosinophilia (higher levels of eosinophilic white blood cell) with evidence of organ damage. The prevalence of HES is unknown, and further research is yet to be done to understand these disorders. HES initially was considered to be idiopathic, but recent advances have paved the way for subclassification. It can be divided into three categories: primary/neoplastic, secondary/reactive, and idiopathic. To date, there are no published data on epidemiology of the disease. An improved approach to HES diagnosis in routine practice and creation of patient registries are essential steps before a reliable estimation of true prevalence can be made. What is know is that HES predominantly affects males, with an estimated male to female ratio ranging between 4 and 9 to 1. Diagnosis is made by an absolute eosinophil count >1500 cells/microliter, associated organ damage and exclusion of other known causes of eosinophilia. Being not any other recognized marker for this condition, HES can be difficult to diagnose as the symptoms it produces are associated with a variety of other disorders.
Patients presenting with eosinophilia will need a complete workup ruling out allergic disorders, infections, vascular-related disorders, malignancy, drug-related, and gastrointestinal or pulmonary related conditions. Symptoms include skin rashes, itching, asthma, shortness of breath, abdominal pain, vomiting, diarrhea, arthritis, muscle inflammation, congestive heart failure, deep venous thrombosis and anemia. Not so many drug options are available for the treatment. The current cornerstone treatment for HES consists of 1mg/kg/day or 60mg/day of steroids, but treatment with tyrosine kinase inhibitors and monoclonal antibodies (biologicals) are emerging. Indeed, for those cases of HES with recongnized bone marrow clonality, like for hypereosinophilia associate with myeloproliferative diseases ((M-HES), treatment with tyrosine kinase inhibitors like imatinib is speicifc. This is due to a specific fusion protein, called FIP1LI/PDGFRA. Since circulating cytolkinse like GM-CSF, IL-3 and IL-5 work as growth factors for eosinophilic granulocytes, the employment of monoclonal antibodies directed against these proteins (or their receptors) is deemed rational.
Yesterday, the U.S. FDA approved Nucala (mepolizumab) for adults and children aged 12 years and older with for six months or longer without another identifiable non-blood related cause of the disease. The new indication for Nucala is the first approval for HES patients in nearly 14 years. Nucala was evaluated in a randomized, double-blind, multicenter, placebo-controlled trial in 108 patients with HES. In the study, patients were randomly assigned to receive Nucala or placebo by injection every four weeks. The trial compared the proportion of subjects who experienced a HES flare during the 32-week treatment period. A HES flare was defined as worsening of clinical signs and symptoms of HES or increasing eosinophils (allergy-related white blood cells) on at least two occasions. The trial compared the proportions of patients with at least one flare over a 32-week treatment period, as well as the time to the first flare. Fewer patients in the Nucala treatment group (28%) had HES flares compared to patients in the placebo group (56%), with a 50% relative reduction.
In addition, the time to the first HES flare was later, on average, for patients treated with Nucala vs. placebo. The most common side effects of Nucala in patients with HES include: upper respiratory tract infection and pain in extremities (such as the hands, legs and feet). Herpes zoster (shingles) infections have occurred in patients receiving Nucala. Health care providers should consider vaccination if medically appropriate. For the treatment of HES, Nucala received orphan drug designation, which provides incentives to assist and encourage drug development for rare diseases. Additionally, the application was granted fast track designation and priority review. The FDA is granting the approval to GlaxoSmithKline of Research Triangle Park, North Carolina. Nucala is also FDA-approved for patients aged 6 years and older with severe asthma with an eosinophilic phenotype and for adult patients with eosinophilic granulomatosis with polyangiitis, a rare autoimmune condition that causes blood vessel inflammation.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Harish A, Schwartz SA. Clin Rev Allergy Immunol. 2020; 59(2):231.
Roufosse F, Kahn JE et al. J Allergy Clin Immunol. 2020 Sep 18.
Forero Molina MA et al. J Allergy Clin Immunol Pract. 2020 Aug 31.
Wu J, Smogorzewski J. J Dermatolog Treat. 2020 Jun 9:1-7.