The Many Faces of

Neutrophilic Eccrine Hidradenitis

DISCUSSION______________________________________________________________________

• NEH is a neutrophilic dermatosis of the eccrine glands. • To date, adults receiving chemotherapy (most commonly cytarabine as seen in our patient) for AML remains the

most common presentation reported in literature.2

• Of note, neutrophils may be absent on histology in chemotherapy-induced neutropenic patients termed “chemotherapy-induced eccrine hidradenitis”.2

• NEH may rarely occur in patients with no previous treatment or following methotrexate (potential etiology in our case), granulocyte-colony stimulating factor, acetaminophen, bleomycin, anthracyclines, 5-fluorouracil, taxanes, cyclophosphamide, vinca alkaloids, imatinib mesylate, or upon initiation of zidovudine.2,4

• Infrequently, NEH has been reported in association with other hematological malignancies, solid tumors, Behçet’s disease, hemodialysis, or systemic infection with HIV, Streptococcus, Serratia, Nocardia, Enterobacter, and Staphylococcus aureus.3,5

• Clinically, NEH most often presents in febrile adults as a self-limited eruption of non-tender to tender, erythematous papules and plaques of the face, trunk, and extremities on an average of 9.7 days following drug exposure.3,4,6 Less frequently, as a polymorphous eruption of papules, nodules, pustules, purpura, urticaria, or as plaques mimicking cellulitis which may make it difficult to distinguish from other neutrophilic dermatoses such as Sweet’s syndrome and pyoderma gangrenosum.1,3,6

• Rarely, an idiopathic variant of NEH presents in children featuring lesions limited to the palms and soles referred to as “palmoplantar eccrine hidradenitis”, thought to be the result of mechanical and/or thermal trauma in healthy children.5

• Regardless of etiology, the eccrine glands and coils serve as the ultimate target of destruction, usually a result of drug-induced neutrophilic chemotaxis following stimulation by inflammatory mediators such as tumor necrosis factor-alpha.4,5 resulting in damage and necrosis of eccrine epithelium.3,4,6

• Alternatively, NEH may be considered along the neutrophilic dermatoses spectrum rather than a distinct entity, a paraneoplastic phenomenon, or in healthy individuals suggesting underlying sweat gland abnormalities.3

• Diagnosis is confirmed by skin biopsy showing an infiltration of neutrophils, and possibly necrosis around and within the eccrine glands and ducts, often with edema and extravasation of red blood cells in the dermis.1,5

• Exclusion of infection is paramount in the prevention of life-threatening complications and unnecessary administration of antibiotics or changes in chemotherapy regimens.3

• NEH tends to be self-limited, although relapse may occur upon re-exposure to an offending agent.3

• Treatment is supportive with topical or systemic corticosteroids and analgesics if needed.3

CONCLUSION______________________________________________________________________

• Historically, NEH is an uncommon neutrophilic dermatosis affecting the eccrine glands that is mostly known to occur in adults receiving chemotherapy for AML. However, NEH should also be considered in any child receiving chemotherapy presenting with fever and a polymorphous eruption.

• Clinicians must broaden their differential diagnosis to include potentially life-threatening mimickers such as opportunistic infections or other neutrophilic dermatoses with systemic features.

• Biopsy is key to establishing a definitive diagnosis. • Treatment is mainly supportive with topical corticosteroids and analgesics as needed.

REFERENCES______________________________________________________________________

1. Bassas-Vila J, Fernandez-Figueras MT, Romani J, Ferrandiz C. Infectious Eccrine Hidradenitis: A Report of 3 Cases and A Review of the Literature. Actas Dermosifiliogr. 2014; 105(2): e7-e12. 2. Copaescu A-M, Castilloux J-F, Chababi-Atallah M, Sinave C, Bertrand J. A Classic Clinical Case: Neutrophilic Eccrine Hidradenitis. Case Rep Dermatol. 2013; 5: 340-346.3. Lee WJ, Kim CH, Chang SE, Lee MW, Choi JH, Moon KC, Koh JK. Generalized Idiopathic Neutrophilic Eccrine Hidradenitis in Childhood. Int J Dermatol. 2010; 49: 75-78. 4. Shih J-H, Huang Y-H, Yang C-H, Yang L-C, Hong H-S. Childhood Neutrophilic Eccrine Hidradenitis: A Clinicopathologic and Immunohistochemical Study of 10 Patients. J Am Acad Dermatol. 2005; 52(6): 963-966.5. Yeh I, George E, Fleckman P. Eccrine Hidradenitis Sine Neutrophils: A Toxic Response to Chemotherapy. J CutanPathol. 2011; 38: 905-910. 6. Grillo E, Vano-Galvan S, Gonzalez C, Pedro J. Letter: Neutrophilic Eccrine Hidroadenitis with Atypical Findings. Dermatology Online Journal. 2011. 17(9): 14.

INTRODUCTION_______________________________________________________________________

• Neutrophilic eccrine hidradenitis (NEH) is an uncommon neutrophilic dermatosis of the eccrine sweat glands.1

NEH was most often reported in adult patients receiving induction chemotherapy, notably, cytarabine for acute myeloid leukemia (AML), characterized by self-limited eruption of erythematous papules and plaques.2

• NEH has since been described in association with other malignancies, infection, and following the ingestion of related immunomodulators and acetaminophen.2

• Featured is a case of NEH presenting as a persistent polymorphous eruption in a child receiving intensification chemotherapy for an even rarer, underlying Philadelphia-chromosome positive acute lymphoblastic leukemia.

PRESENTATION_____________________________________________________________________

• An 8-year-old Hispanic male with Ph+ ALL presented to the emergency department with a two-day history of fever and rash on the extensor arms, cheeks, lower trunk, and legs which began within two hours of leucovorin infusion, nearly 2 days following administration of methotrexate and cytarabine.

• Additional history included sulfa-induced urticarial eruption, seizure disorder, recurrent pneumonia and otitis media, asthma, and anemia requiring multiple transfusions.

• Home medications included dasatinib, levetiracetam, and acetaminophen.• Physical examination revealed symmetric, non-tender, blanchable, edematous, erythematous, follicular

papules and plaques with central dusky coloration of the extensor arms, lower back, buttocks, anterolateral thighs, and lateral lower legs (Figure 1-3). Pinpoint, skin-colored to pink follicular papules and pustules of the cheeks, extensor arms, and abdomen (Figure 4), superficial erosions with hemorrhagic crusts of the lower lip and a pink velvety dorsal tongue were also noted. Scalp alopecia prominent. Palms and soles were spared.

• Histology showed hyperkeratosis, clefting below the granular layer, vacuolar interface dermatitis, follicular plugging, dyskeratotic cells and neutrophils within eccrine gland coils (Figure 5-6). Culture and DIF negative.

• Laboratory tests revealed leukopenia with neutropenia, lymphocytosis, mild monocytosis, anemia, thrombocytopenia, elevated transaminases, hypoproteinemia, and hypoalbuminemia.

• Renal function tests, CRP, coagulation profile, cultures, and chest radiograph were unremarkable.• Serology negative for anti-streptolysin O, human immunodeficiency virus-1/-2, hepatitis B and C virus,

Mycoplasma pneumoniae IgM, parvovirus B19, Epstein-Barr virus.• PCR negative for parvovirus, adenovirus, cytomegalovirus, human herpes virus-1/-2/-6/-7, and enterovirus.• Bone marrow aspiration revealed minimal residual disease with erythroid and granulocytic hyperplasia. • Findings were consistent with NEH, and in all likelihood, the result of cytarabine. However, methotrexate as

the offending agent could not be excluded. Further, dasatinib has been reported to cause follicular papular and pustular eruptions, similar to the acneiform and keratosis pilaris-like eruption seen in our patient.

• Treatment included empiric antibiotics and antifungals pending negative cultures and topical corticosteroid. • One month later, the patient presented to the dermatology clinic with minimal improvement of the eruption

and was started on oral prednisolone to further facilitate recovery.

Leslie Mills, DO, Robin Shecter, DO, FAOCDJFK Medical Center-North Campus, West Palm Beach, Florida

Neutrophilic Eccrine Hidradenitis SpectrumPalm Beach Consortium for

Graduate Medical Education

JFK Medical Center-North CampusPalms West Hospital

St. Lucie Medical CenterUniversity Hospital & Medical Center

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