Continuing Education Activity

Neutrophilic eccrine hidradenitis is an uncommon disease affecting the eccrine glands, leading to eccrine unit necrosis. It is most commonly seen in adults receiving cytarabine as a part of the induction chemotherapy for the treatment of hematological malignancy. The diagnosis of neutrophilic eccrine hidradenitis may signify that the patient has an underlying malignancy or relapse of previous malignancy. In newly diagnosed neutrophilic eccrine hidradenitis patients with no history of malignancy, the primary care provider should be notified, and age-appropriate cancer screening guidelines should be followed. This activity reviews the evaluation, treatment, and prognosis of neutrophilic eccrine hidradenitis and examines the role of the interprofessional team in evaluating and improving care for patients with this condition.

Objectives:

• Describe the risk factors for neutrophilic eccrine hidradenitis.
• Review the presenting features of neutrophilic eccrine hidradenitis.
• Outline the management of neutrophilic eccrine hidradenitis.
• Describe how an optimally functioning interprofessional team approach to coordinate care and enhance outcomes for patients with neutrophilic eccrine hidradenitis.

Introduction

Neutrophilic eccrine hidradenitis (NEH) is a benign, rare condition that was initially used to describe the skin eruptions observed in acute myelogenous leukemia (AML) patients receiving systemic chemotherapy. It can be considered a reactive disorder and is commonly associated with malignancies that include other leukemias, Hodgkin lymphoma, and solid tumors. Since its introduction in 1982, neutrophilic eccrine hidradenitis is frequently described with other neutrophilic dermatoses. these are a group of skin disorders characterized by normal neutrophilic infiltrates in the predominantly dermal portion of the skin, with no identifiable source of infection. [1]

Etiology

Neutrophilic eccrine hidradenitis is a benign, self-limiting neutrophilic dermatosis of unknown etiology. However, neutrophilic eccrine hidradenitis has been observed with the following medications: acetaminophen, minocycline, granulocyte colony-stimulating factors, cyclophosphamide, methotrexate, carbamazepine, cetuximab, BRAF inhibitors, bleomycin, methotrexate, 5-fluorouracil, and antiretroviral medications. Before neutrophilic eccrine hidradenitis is diagnosed, practitioners usually rule-out infectious causes; nevertheless, biopsy results from several cases of active bacterial and viral infections were reported to show histological changes consistent with neutrophilic eccrine hidradenitis. Of note, heat damage of eccrine glands may elicit neutrophilic eccrine hidradenitis in the pediatric population.[1][2]

Epidemiology

The frequency of neutrophilic eccrine hidradenitis is not well studied or known. Neutrophilic eccrine hidradenitis has a slight male predominance and has been reported in individuals between six months to 79 years of age.[2]

Pathophysiology

The pathogenesis of neutrophilic eccrine hidradenitis is poorly understood. There is evidence supporting a direct cytotoxic effect of chemotherapy as the initial trigger in neutrophilic eccrine hidradenitis pathophysiology. For instance, intradermal bleomycin injections caused pathologic changes consistent with those seen in neutrophilic eccrine hidradenitis. Interestingly, patients with malignancies who develop neutrophilic eccrine hidradenitis typically do so after their first course of chemotherapy.[3][4]

One proposed mechanism emphasizes the direct cytotoxic effect of the offending agent. The release of toxic byproducts secondary to cell death promotes neutrophil recruitment to the eccrine glands, while another model suggests that neutrophilic eccrine hidradenitis is a reactive process in response to an underlying malignancy (paraneoplastic phenomenon). Another model suggests abnormal neutrophil response and function in response to some offending agent (drug versus malignancy).[5]

Histopathology

Biopsy specimens reveal a dense neutrophilic infiltrate surrounding and infiltrating within and around eccrine glands, with necrotic eccrine epithelial cells. Intraductal abscess formation may be seen as well. Neutropenic patients may have sparse or absence of neutrophils in the dermal layer, but eccrine gland necrosis is evident. Thus, the hallmark histological finding in neutrophilic eccrine hidradenitis is necrosis of the eccrine unit. Moreover, the following histological changes may also be evident in neutrophilic eccrine hidradenitis: apocrine gland necrosis, squamous syringometaplasia, dermal hemorrhage, epidermal spongiosis, basilar vacuolization, focal keratinocyte necrosis, mucin deposition, and panniculitis.[1]

History and Physical

The classic presentation of neutrophilic eccrine hidradenitis is seen in acute myelogenous leukemia patients receiving chemotherapy, most commonly with cytarabine. Neutrophilic eccrine hidradenitis can present as quickly as two days or up to 2 years after chemotherapy initiation. Also, there have been documented cases of neutrophilic eccrine hidradenitis in acute myelogenous leukemia and chronic myelogenous leukemia (CML) patients naïve to chemotherapeutic agents. Clinically patients present with erythematous papules and plaques most frequently in the face, back, trunk, and extremities.[5]

Regardless of the patients’ past medical history, neutrophilic eccrine hidradenitis patients frequently present with fever, in addition to the solitary or multiple lesions that are best described as dark red, violaceous macules, papules, nodules, or plaques.[6]

Neutrophilic eccrine hidradenitis favors the trunk and limbs. Half the patients are asymptomatic, while lesional pain and tenderness are the most common complaints. Because of its variable presentations, it can be challenging to differentiate neutrophilic eccrine hidradenitis from other neutrophilic dermatoses that are also commonly associated with malignancies.[6]

Neutrophilic eccrine hidradenitis differential diagnoses include, but are not limited to, other neutrophilic dermatoses such as acute febrile neutrophilic dermatosis (Sweet syndrome), acute urticaria, graft versus host disease, erythema nodosum, erythema multiforme, cellulitis, and erysipelas.[7]

Evaluation

Definitive diagnosis of neutrophilic eccrine hidradenitis requires a skin punch biopsy demonstrating a dense neutrophilic infiltrate of the eccrine unit with necrosis and dermal edema. A routine complete blood count (CBC) should be ordered to confirmed neutrophilic eccrine hidradenitis cases (preliminary workup for possible underlying hematological malignancy). Nonspecific inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) can be considered. Tissue culture is critical for detecting infectious causes.[8][9]

Treatment / Management

There is no widely accepted treated for neutrophilic eccrine hidradenitis; supportive care is recommended. In general, neutrophilic eccrine hidradenitis is a self-limiting disease and does not require therapy. In most cases, the lesions resolve spontaneously within a month. The use of corticosteroids, topical and systemic, is debatable. Nonetheless, it is well-recognized that steroids should be used with caution in neutropenic patients. Symptomatic management of fever and, or, pain is strongly recommended. Colchicine has been used successfully to treat otherwise healthy, neutrophilic eccrine hidradenitis patients.[10]

Many patients experience recurrent neutrophilic eccrine hidradenitis with subsequent courses of chemotherapy; if the patient’s neutrophilic eccrine hidradenitis is associated with a specific chemotherapeutic agent, one case report recommends using dapsone 100 mg daily, for 48 hours, before drug rechallenge.[11]

Differential Diagnosis

• Acute or chronic urticaria
• Vasculitis syndrome
• Drug eruptions
• Erythema multiforme/nodosum
• Leukemia cutis [5]

Prognosis

Recurrence of symptoms is common in patients administered chemotherapy. However, neutrophilic eccrine hidradenitis runs a self-limited course and does not worsen the prognosis for that particular malignancy.[11]

Postoperative and Rehabilitation Care

Most patients need to follow up care to ensure that there is a resolution of the skin lesions.[11]

Consultations

The condition is best treated by an oncologist and a dermatologist who specializes in oncology.[2]

Pearls and Other Issues

Neutrophilic eccrine hidradenitis is an uncommon disease affecting the eccrine glands, leading to eccrine unit necrosis.

It is most commonly seen in adults receiving cytarabine as part of the induction chemotherapy for the treatment of hematological malignancy.

The diagnosis of neutrophilic eccrine hidradenitis may signify that the patient has an underlying malignancy (paraneoplastic process), or relapse of previous malignancy. In newly diagnosed neutrophilic eccrine hidradenitis patients with no history of malignancy, their primary care provider should be notified, and age-appropriate cancer screening guidelines should be followed. 

A skin biopsy is necessary to confirm the diagnosis of neutrophilic eccrine hidradenitis.

If the patient has a cancer history, the managing hematologist, and, or oncologist should be informed.

There is no widely accepted treated for neutrophilic eccrine hidradenitis; supportive care is recommended.[2][12]

Enhancing Healthcare Team Outcomes

Treatment of neutrophilic eccrine hidradenitis is supportive; usually requiring interprofessional management of clinicians of multiple specialties and supportive care of specialty-trained dermatology and oncology nurses. The nurses monitor patient's conditions, administer ordered treatments, and educate patients about skincare. Oncology pharmacists should be aware of this condition, review the use of medications with patients, and provide feedback to the team. [Level 5]