Background
Neutrophilic eccrine hidradenitis (NEH) was initially described in acute myelogenous leukemia (AML) patients undergoing chemotherapy. [1, 2] Neutrophilic eccrine hidradenitis has since been reported in persons with various neoplastic and nonneoplastic conditions and in otherwise healthy individuals; however, most documented cases have continued to be observed in the setting of AML, usually in association with chemotherapy; the name toxic erythema of chemotherapy has been proposed. [3] It has also been associated with other drugs, including pegfilgrastim, the antiplatelet agent ticagrelor, and infliximab, as well as various infections. [4, 5, 6, 7, 8]
Patients with this uncommon, self-limited condition usually present with fever and nonspecific cutaneous lesions. Children may develop a palmoplantar variant of neutrophilic eccrine hidradenitis unassociated with underlying disease. [9] Plantar neutrophilic hidradenitis is associated with Pseudomonas overgrowth in sweaty or wet sneakers and has also been dubbed Pseudomonas hotfoot. A skin biopsy specimen demonstrating characteristic pathologic changes of the eccrine glands is required to confirm a diagnosis of neutrophilic eccrine hidradenitis.
Also see the Medscape articles Acute Myelogenous Leukemia and Chronic Myelogenous Leukemia.
Pathophysiology
The mechanism(s) of neutrophilic eccrine hidradenitis (NEH) is unknown, although neutrophilic eccrine hidradenitis pathologic changes observed with intradermal bleomycin injections support a direct toxic effect of chemotherapy. More than 70% of oncology patients who develop neutrophilic eccrine hidradenitis do so after their first course of chemotherapy. [10] Cases linked to chemotherapeutic agents have developed at a wide range of 2 days to 2 years after initiation. Some patients experience recurrences of the cutaneous eruption upon reintroduction of the chemotherapeutic regimens. A diagnosis of toxic erythema of chemotherapy has been proposed for this group of disorders, to emphasize the overlapping clinical and histological features with similar eruptions. [3]
Reports of neutrophilic eccrine hidradenitis heralding the onset of both AML [11] and chronic myelogenous leukemia, [12] the relapse of AML, [13] and being induced by granulocyte colony-stimulating factor [14] suggest that the condition is in the spectrum of other neutrophilic dermatoses that have been observed in patients with cancer: erythema elevatum diutinum, intraepidermal immunoglobulin A (IgA) pustulosis, pyoderma gangrenosum, subcorneal pustular dermatosis, Sweet syndrome (and it localized variant, neutrophilic dermatosis/pustular vasculitis of the dorsal hand), and vasculitis. The inflammatory infiltrate of mature polymorphonuclear leukocytes is the unifying characteristic of this group of conditions. [10]
Cases of neutrophilic eccrine hidradenitis in otherwise healthy individuals, [15] occurring with a variety of nonchemotherapeutic agents, in Behçet disease, [16] in chronic granulomatous disease, [17] and in the setting of various infections suggest it could simply be an altered inflammatory response to nonspecific stimuli. Neutrophilic eccrine hidradenitis in young children may be triggered by thermal damage of eccrine glands. [9]
Etiology
The cause of neutrophilic eccrine hidradenitis (NEH) is unknown. A direct toxic effect of chemotherapy and a paraneoplastic mechanism have both been proposed to explain neutrophilic eccrine hidradenitis in the context of malignancy. Cases of neutrophilic eccrine hidradenitis resolving after withdrawal of chemotherapy and recurring upon reinstitution of the same regimen favor the former. Also supporting a direct toxic drug response is a study showing that the intradermal injection of bleomycin can yield local neutrophilic eccrine hidradenitis changes. [18] However, skin lesions arising after chemotherapy have developed anywhere from 2 days to 2 years later. A diagnosis of toxic erythema of chemotherapy has been proposed for this group of disorders, to emphasize the overlapping clinical and histologic features with similar eruptions. [3]
Favoring a paraneoplastic process are case reports of neutrophilic eccrine hidradenitis heralding the onset of both AML [11] and chronic myelogenous leukemia [12] and the relapse of AML. [13] Neutrophilic eccrine hidradenitis has also been observed in otherwise healthy individuals [15] ; in chronic granulomatous disease [17] ; in Behçet disease [16] ; with acetaminophen [19] ; with granulocyte colony-stimulating factor [14] and pegfilgrastim [5] ; with cyclophosphamide therapy for lupus [20] ; with methotrexate therapy for actinic reticuloid [21] ; with carbamazepine usage [22] ; with cetuximab treatment [23] ; with BRAF inhibitors [24] ; with antiretroviral medications [25] ; in azathioprine hypersensitivity syndrome [26] ; ticagrelor [4] ; FOLFOX (folinic acid, fluorouracil, and oxaliplatin) chemotherapy [27] ; infliximab use [8] ; and with HIV, Serratia, Enterobacter,Nocardia, Staphylococcus, Streptococcus, Mycobacterium chelonae, and COVID-19 [6, 7] infections.
Epidemiology
Frequency
The frequency of neutrophilic eccrine hidradenitis (NEH) is unknown.
Sex
A slight male predominance is found in cases of neutrophilic eccrine hidradenitis. [28]
Age
Neutrophilic eccrine hidradenitis has been reported in individuals as young as 6 months and as old as 79 years.
Prognosis
Many patients experience recurrent symptoms with subsequent courses of chemotherapy. One patient avoided painful recurrences with prophylactic dapsone. Possible hematologic toxicity with dapsone in the setting of chemotherapy regimens is a concern. [29] Neutrophilic eccrine hidradenitis (NEH) is typically a self-limited process. It does not appear to portend a worse prognosis for the underlying malignancy when occurring in that setting.
-
Courtesy of Jeffrey P. Callen, MD.
-
Neutrophilic infiltrate on hematoxylin and eosin stain (100X). Courtesy of Jeffrey P. Callen, MD, and Vilma Fabre, MD.
