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Neutrophilic Eccrine Hidradenitis in a Primary CNS Lymphoma Patient Receiving High-Dose Chemotherapy

Neutrophilic Eccrine Hidradenitis (NEH) is a rare inflammatory neutrophilic dermatosis that primarily affects eccrine sweat glands. Although it has been described in various malignancies and with therapeutic agents, it is most frequently associated with cytarabine-based induction chemotherapy for acute myelogenous leukemia. We report a rare case of NEH in a 63-year-old male with a medical history significant for primary CNS lymphoma. The patient was treated with high-dose thiotepa, busulfan, and cyclophosphamide (BuCy) followed by autologous stem cell transplantation, which was complicated by bacteremia and septic shock. Approximately three weeks after chemotherapy, he developed localized bright red, desquamating plaques on his bilateral outer hips, posterior upper thighs, and buttocks. Histological findings revealed neutrophils infiltrating and surrounding the eccrine glands accompanied by squamous syringometaplasia, apoptotic keratinocytes, and basovacuolar changes. This case serves to highlight that NEH should be considered in the differential diagnosis of erosive, erythematous plaques, especially in patients with lymphoproliferative tumors receiving high-dose chemotherapy, in order to provide appropriate clinical management.


Introduction
Chemotherapy with thiotepa, busulfan, and cyclophosphamide (BuCy) followed by autologous stem cell transplantation has been adopted as the treatment of the primary Central Nervous System (CNS) lymphoma [1]. High-dose chemotherapy has been associated with Neutrophilic Eccrine Hidradenitis (NEH) in patients with acute myelogenous leukemia [2]. NEH is described as a neutrophilic dermatosis characterized by neutrophilic infiltrates predominantly in the dermis without any identifiable source of infection [3]. To our knowledge, we present the first case of Neutrophilic Eccrine Hidradenitis (NEH) in an adult patient receiving high-dose chemotherapy for primary CNS lymphoma.

Case Report
A 63-year-old male with a history of primary CNS lymphoma presented with fever and erythematous plaques on the buttocks and lower extremities. Three weeks prior to presentation, the patient was treated with high-dose chemotherapy (thiotepa and BuCy) followed by autologous stem cell transplantation, which was complicated by Klebsiella and Pseudomonas bacteremia and septic shock. On physical examination, a few well-circumscribed erythematous erosions with overlying white crust were noted on the outer thighs ( Figure 1). On the buttocks and upper posterior thighs were bright red, eroded plaques with overlying fine white desquamation. A punch biopsy was performed on his right anterior thigh out of concern for acute graft versus host reaction versus a drug reaction.  Histological examination revealed prominent peri-eccrine inflammation with neutrophils and squamous syringometaplasia in the superficial and mid-dermis ( Figure 2). Interface dermatitis with apoptotic keratinocytes and bilateral basovacuolar change with an underlying superficial and deep mixed inflammatory infiltrate of predominantly neutrophils were also observed. There was no evidence of vasculitis or hemorrhage. The fungal and bacterial cultures were negative. These findings were most consistent with NEH secondary to high-dose thiotepa and BuCy. While the patient's history of recent autologous stem cell transplantation was concerning for acute graft versus host reaction, the changes in eccrine glands seen in NEH are not observed in this diagnosis. The patient was treated with triamcinolone 0.1% ointment and silver sulfadiazine cream twice daily.
NEH clinically manifests 2 days to 3 weeks following the induction of chemotherapy [2]. As demonstrated in Table 1, it presents as erythematous plaques typically located on the face, trunk, palms, or extremities, with or without associated fever or neutropenia [2,5,6]. Differential diagnosis may include erythema multiforme, leukemia cutis, drug hypersensitivity, vasculitis, bullous pyoderma, Sweet's syndrome and pyoderma gangrenosum [17].  The diagnosis of NEH is based on histological findings [18]. It is characterized by dense neutrophilic infiltrating and surrounding the eccrine glands, which may be accompanied by dermal edema and/or hemorrhage, squamous syringometaplasia, and necrosis of the eccrine coils and glands [2]. Epidermal spongiosis, basal vacuolization, and focal necrotic keratinocytes may also be present [9]. These findings in our case confirmed the diagnosis. Histopathological differential diagnosis includes, but is not limited to, acute urticaria, graft versus host disease, erythema nodosum, erythema multiforme, cellulitis, sweet syndrome, and erysipelas [3].
The pathogenesis of NEH has not been well-characterized. Harris et al., postulated that NEH may arise secondary to a direct cytotoxic effect of a therapeutic agent secreted in the sweat on the eccrine glands [19]. The damage of the glands may stimulate an inflammatory response and neutrophilic chemotaxis, which would lead to cellular damage and necrosis of the epithelial cells [2]. This may account for a majority of NEH cases, including our case, in patients receiving highdose chemotherapy. In contrast, other investigators proposed that NEH is part of the spectrum of neutrophilic dermatoses [18].
NEH is generally a benign, self-limiting condition [6]. Current treatment includes non-steroidal anti-inflammatory drugs and topical corticosteroids, which should be used with caution in patients with neutropenia [2]. Shear et al., demonstrated that administration of dapsone 48 hours prior to chemotherapy prevented recurrent NEH in a patient [20]. It is also important to exclude infection as well as another differential diagnosis by fungal and bacteria cultures to avoid unnecessary use of antibiotic or changes in chemotherapy regimens [11,17].

Conclusion
NEH is a neutrophilic dermatosis characterized by neutrophilic infiltrates within and around eccrine glands. It should be considered in the differential diagnosis of eroded, erythematous plaques, especially in patients receiving high-dose chemotherapy for primary CNS lymphoma. A diagnosis of NEH should be based on histological findings to avoid unnecessary use of antibiotics and changes in chemotherapy regimens.