Abstract:

Hypereosinophilic syndrome is defined as persistent eosinophilia (>1500/µL for more than six months) associated with organ involvement, excluding secondary causes. It is a rare, potentially lethal disease that should be considered in cutaneous conditions associated with hypereosinophilia. We report a case of erythroderma as a manifestation of hypereosinophilic syndrome. A 36-year-old male with no comorbidities presented progressive erythroderma, pruritus, peripheral neuropathy, and eosinophilia in the previous seven months. No mutations were found in FIP1L1/PDGFRA. Patient experienced rapid remission in response to oral prednisone and hydroxyurea. Cutaneous manifestations may be the only evidence of hypereosinophilic syndrome. Genotyping excludes myeloproliferative disease, thereby orienting treatment and prognosis.

Keywords:
Eosinophilia; Polyneuropathies; Dermatitis, Exfoliative

CASE REPORT

Patient was a 36-year-old Brazilian male physician of Japanese descent with no comorbidities or atypical signs. Six years previously he presented intermittent erythematous papules on the trunk and face, in addition to pruritus aggravated by heat or alcohol intake. Six months previously he evolved with erythroderma, treated with cyclosporine (3mg/kg/d), hydration, and topical corticosteroids, with partial improvement. On physical examination: erythroderma, facial infiltration, and infiltrated erythematous plaques (mainly cubital and popliteal), xeroderma, thickening of the greater auricular, fibular, radial, and ulnar nerves with reduced strength in hands (Figure 1). Anatomical pathology of the skin revealed acanthosis, spongiosis, and superficial lymphocytic infiltrate with eosinophils (Figure 2). Complete blood count: eosinophilia 2,812U/µL; IgE 1,164 kU/L (ULN 114kU/L), and DHL 596U/L (ULN 225U/L). Ultrasound of the wrists showed thickening of the median nerve with normal morphology of the carpal tunnel. Normal echocardiogram, and abdominal tomography showed periaortic lymph nodes slightly increased in number.

DISCUSSION

Hypereosinophilic syndrome (HES) is characterized by persistently elevated peripheral eosinophil count (> 1,500/µL) associated with symptomatic organ involvement, excluding secondary causes of eosinophilia (Chart 1).¹1 Simon HU, Rothenberg ME, Bochner BS, Weller PF, Wardlaw AJ, Wechsler ME, et al. Refining the definition of hypereosinophilic syndrome. J Allergy Clin Immunol. 2010;126:45-9. It is classified as myeloproliferative (HES-M), secondary or reactive (HES-L), and idiopathic (HES-I) (Chart 2).²2 Valent P, Klion AD, Horny HP, Roufosse F, Gotlib J, Weller PF, et al. Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes. J Allergy Clin Immunol. 2012;130:607-612.e9.

HES is a rare disease (5,000 cases/year in the United States of America), potentially fatal, and the organs most frequently involved are skin, lungs, intestine, heart, kidneys, eyes, and peripheral nervous system. The most serious complication is cardiac, which should be investigated in all cases. In adults, the syndrome is more common in males (ratio 9:1), and mean age at onset is 50 years. Investigation of organ involvement and sub-classification are decisive for treatment and prognosis.³3 Hsieh FH. Hypereosinophilic syndrome. Ann Allergy Asthma Immunol. 2014;112:484-8.^,44 Plötz SG, Hüttig B, Aigner B, Merkel C, Brockow K, Akdis C, et al. Clinical overview of cutaneous features in hypereosinophilic syndrome. Curr Allergy Asthma Rep. 2012;12:85-98.

Cutaneous manifestations of HES require differential diagnosis with urticaria, pruritus sine materia, mycosis fungoides, cutaneous adverse drug reactions, contact dermatitis, and atopic dermatitis. Dermatologists should be alert to pruritic erythematous papules, urticaria, angioedema, dermographism, oral and genital ulcers, centrifugal annular erythema, acral bullae, and erythroderma. Histopathologic examination of the skin lesion is usually nonspecific, with viable eosinophilic infiltration.⁴4 Plötz SG, Hüttig B, Aigner B, Merkel C, Brockow K, Akdis C, et al. Clinical overview of cutaneous features in hypereosinophilic syndrome. Curr Allergy Asthma Rep. 2012;12:85-98.

5 Kazmierowski JA, Chusid MJ, Parrillo JE, Fauci AS, Wolff SM. Dermatologic manifestations of the hypereosinophilic syndrome. Arch Dermatol. 1978;114:531-5.

6 Mahajan VK, Singh R, Mehta KS, Chauhan PS, Sharma S, Gupta M, et al. Idiopathic hypereosinophilic syndrome: a rare cause of erythroderma. J Dermatol Case Rep. 2014;8:108-14.^-77 Abdulsalam MS, Ghanta HC, Pandurangan P, Menon M, Jacob SS. A Case of Erythroderma Secondary to Hypereosinophilia. J Clin Diagn Res. 2016;10:OD15-6.

In an endemic country like Brazil, a presentation with polyneuropathy requires ruling out leprosy, which is unlikely in this case because of the pruritus and histology.

In this case, treatment began with prednisone 1mg/kg/day, with important improvement in the skin lesions, eosinophilia (580/µL), and pruritus after 30 days. Bone marrow biopsy did not show neoplastic infiltration, FISH cytogenetic test did not reveal deletion or translocation of the FIP1L1 and PDGFRA genes, JAK2 mutation was negative, and immunophenotyping did not show clonal lymphocyte populations. Adjuvant therapy with hydroxyurea was scheduled in conjunction with the Department of Hematology.

The case was classified as HES-I based on the absence of lymphocytic phenotypical abnormalities or genetic alterations. Presence of peripheral neuropathy, absence of atopic signs, and worsening of the clinical picture with alcohol intake were characteristic. High IgE levels, good response to corticosteroid therapy, and low serum tryptase level and eosinophil count < 100,000/µL are associated with better prognosis. Therapeutic success in HES-I has been reported with tofacitinib and mepolizumab.⁴4 Plötz SG, Hüttig B, Aigner B, Merkel C, Brockow K, Akdis C, et al. Clinical overview of cutaneous features in hypereosinophilic syndrome. Curr Allergy Asthma Rep. 2012;12:85-98.^,88 King B, Lee AI, Choi J. Treatment of Hypereosinophilic Syndrome with Cutaneous Involvement with the JAK Inhibitors Tofacitinib and Ruxolitinib. J Invest Dermatol. 2017;137:951-954.

9 Schwartz LB, Sheikh J, Singh A. Current strategies in the management of hypereosinophilic syndrome, including mepolizumab. Curr Med Res Opin. 2010;26:1933-46.^-1010 Noh HR, Magpantay GG. Hypereosinophilic syndrome. Allergy Asthma Proc. 2017;38:78-81.

Diagnosis of HES is often delayed due to its pleomorphic dermatological manifestations and insidious evolution. It is thus crucial that in all cases of erythroderma, HES should be considered as a differential diagnosis.⁶6 Mahajan VK, Singh R, Mehta KS, Chauhan PS, Sharma S, Gupta M, et al. Idiopathic hypereosinophilic syndrome: a rare cause of erythroderma. J Dermatol Case Rep. 2014;8:108-14.^,77 Abdulsalam MS, Ghanta HC, Pandurangan P, Menon M, Jacob SS. A Case of Erythroderma Secondary to Hypereosinophilia. J Clin Diagn Res. 2016;10:OD15-6.

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