You are in: eMedicine Specialties > Dermatology > DISEASES OF THE ADNEXA Neutrophilic Eccrine HidradenitisArticle Last Updated: May 2, 2008AUTHOR AND EDITOR INFORMATIONSection 1 of 11
  Author: Joseph C Pierson, MD, Chief, Dermatology Service, United States Military Academy Joseph C Pierson is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology Coauthor(s): Christine C Tam, MD Editors: Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Medicine, Professor of Pediatrics, Professor of Pathology, Professor of Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School; Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center; Warren R Heymann, MD, Head, Division of Dermatology, Professor, Department of Internal Medicine, University of Medicine and Dentistry of New Jersey; Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania; Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center Author and Editor Disclosure Synonyms and related keywords: NEH, acute myelogenous leukemia, AML, chemotherapy-associated eccrine hidradenitis, drug-associated eccrine hidradenitis, infectious eccrine hidradenitis, neutrophilic dermatoses, chemotherapy, intradermal bleomycin injections, Sweet syndrome, atypical pyoderma gangrenosum INTRODUCTIONSection 2 of 11
  BackgroundNeutrophilic eccrine hidradenitis (NEH) was initially described in acute myelogenous leukemia (AML) patients undergoing chemotherapy.1 NEH 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. Patients with this uncommon, self-limited condition usually present with fever and nonspecific cutaneous lesions. A skin biopsy specimen demonstrating characteristic pathologic changes of the eccrine glands is required to confirm a diagnosis of NEH.
PathophysiologyThe mechanism(s) of NEH is unknown, although NEH pathologic changes observed with intradermal bleomycin injections support a direct toxic effect of chemotherapy. More than 70% of oncology patients who develop NEH do so after their first course of chemotherapy.2 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. Reports of NEH heralding the onset of both AML3 and chronic myelogenous leukemia,4 the relapse of AML,5 and being induced by granulocyte colony-stimulating factor6 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.2 FrequencyInternationalFrequency is unknown. Mortality/MorbidityNEH is typically a self-limited process. It does not appear to portend a worse prognosis for the underlying malignancy when occurring in that setting. SexA slight male predominance is found.13 AgeNEH has been reported in individuals as young as 6 months and as old as 79 years. CLINICALSection 3 of 11
HistoryMost reported cases of NEH have been in patients with AML who are undergoing chemotherapy, frequently with cytarabine. Granulocytopenia may be found in such cases. Other malignancy and chemotherapy associations exist. As noted previously, cases have been documented in AML and chronic myelogenous leukemia patients who were not on chemotherapy. Some otherwise healthy individuals have inexplicably developed biopsy-proven lesions of NEH. Regardless of the clinical setting, patients with NEH develop skin lesions and frequently report fever. Half of the patients are asymptomatic, but pain and tenderness are not uncommon. PhysicalThe cutaneous lesions of NEH are protean. NEH lesions may be solitary or multiple. Erythematous or purpuric macules, papules, nodules, or plaques are described most frequently. Hyperpigmented plaques, annular lesions,14 and sclerodermoid changes15 have also been noted. Tenderness may be elicited. The trunk or limbs are most often involved. NEH simulating orbital cellulitis,16 facial cellulitis,17 and symmetrical ear swelling18 have been documented. CausesThe cause of NEH is unknown. A direct toxic effect of chemotherapy and a paraneoplastic mechanism have both been proposed to explain NEH in the context of malignancy. Cases of NEH 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 NEH changes.19 However, skin lesions arising after chemotherapy have developed anywhere from 2 days to 2 years later. DIFFERENTIALSSection 4 of 11
Acute Febrile Neutrophilic Dermatosis Drug Eruptions Erythema Multiforme Erythema Nodosum Graft Versus Host Disease Pyoderma Gangrenosum Urticaria, Acute Urticaria, Chronic Urticarial Vasculitis
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| Drug Name | Ibuprofen (Ibuprin, Advil, Motrin) |
|---|---|
| Description | DOC for mild to moderate pain. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis. |
| Adult Dose | 400-800 mg PO tid; not to exceed 3.2 g/d |
| Pediatric Dose | 10 mg/kg PO q6-8h; not to exceed 40 mg/kg |
| Contraindications | Documented hypersensitivity; peptic ulcer disease, recent GI bleeding or perforation, renal insufficiency, or high risk of bleeding |
| Interactions | Coadministration with aspirin increases risk of serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently; concurrent use of NSAIDs and cyclosporine may increase cyclosporine levels, nephrotoxicity, and increased plasma creatinine concentrations; concurrent administration of lithium and NSAIDs may result in elevated lithium serum levels leading to lithium toxicity |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Caution in dehydration, CHF, hypertension, and decreased renal and hepatic function; prolonged bleeding may be exaggerated in patients with underlying hemostatic defects; caution in anticoagulation abnormalities or during anticoagulant therapy; GI toxicity (eg, bleeding, ulceration, perforation) can occur in patients treated with long-term administration of NSAIDs |
| Drug Name | Ketoprofen (Oruvail, Orudis) |
|---|---|
| Description | For relief of mild to moderate pain and inflammation. Initially, small dosages are indicated in patients who are small and/or elderly and in those with renal or liver disease. Doses >75 mg do not increase therapeutic effects. Administer high doses with caution, and closely observe patient for response. |
| Adult Dose | 25-50 mg PO q6-8h prn; not to exceed 300 mg/d |
| Pediatric Dose | 3 months to 12 years: 0.1-1 mg/kg PO q6-8h >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity; treatment of peri-operative pain in setting of coronary artery bypass graft (CABG) surgery; patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs |
| Interactions | Coadministration with aspirin increases risk of serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, ACE inhibitors, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently; antihypertensive effects of calcium channel blockers may be antagonized by concomitant administration of NSAIDs (avoid); also avoid NSAIDs in patients receiving tacrolimus immunosuppression, particularly in patients with liver dysfunction; concurrent use of NSAIDs and cyclosporine may increase cyclosporine levels, nephrotoxicity, and plasma creatinine concentrations; concurrent administration of lithium and NSAIDs may result in elevated lithium serum levels leading to lithium toxicity |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Caution in CHF, hypertension, and decreased renal and hepatic function; caution in coagulation abnormalities or during anticoagulant therapy; avoid use of NSAIDs in patients receiving tacrolimus immunosuppression, particularly in patients with liver dysfunction |
| Drug Name | Naproxen (Anaprox, Naprelan, Naprosyn) |
|---|---|
| Description | For relief of mild to moderate pain; inhibits inflammatory reactions and pain by decreasing activity of cyclo-oxygenase, which results in a decrease of prostaglandin synthesis. |
| Adult Dose | 500 mg PO followed by 250 mg q6-8h; not to exceed 1.25 g/d |
| Pediatric Dose | <2 years: Not established >2 years: 2.5 mg/kg/dose PO; not to exceed 10 mg/kg/d |
| Contraindications | Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency |
| Interactions | Coadministration with aspirin increases risk of serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently; concurrent use of NSAIDs and cyclosporine may increase cyclosporine levels, nephrotoxicity, and increased plasma creatinine concentrations; concurrent administration of lithium and NSAIDs may result in elevated lithium serum levels leading to lithium toxicity |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Acute renal insufficiency, interstitial nephritis, hyperkalemia, hyponatremia, and renal papillary necrosis may occur; patients with preexisting renal disease or compromised renal perfusion risk acute renal failure; leukopenia occurs rarely, is transient, and usually returns to normal during therapy; persistent leukopenia, granulocytopenia, or thrombocytopenia warrants further evaluation and may require discontinuation of drug |
| Drug Name | Flurbiprofen (Ansaid) |
|---|---|
| Description | May inhibit cyclo-oxygenase enzyme, which in turn inhibits prostaglandin biosynthesis. These effects may result in analgesic, antipyretic, and anti-inflammatory activities. |
| Adult Dose | 200-300 mg/d PO divided bid/qid |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity |
| Interactions | Coadministration with aspirin increases risk of serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, ACE inhibitors, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently; antihypertensive effects of calcium channel blockers may be antagonized by concomitant administration of NSAIDs (avoid); also avoid NSAIDs in patients receiving tacrolimus immunosuppression, particularly in patients with liver dysfunction; concurrent use of NSAIDs and cyclosporine may increase cyclosporine levels, nephrotoxicity, and increased plasma creatinine concentrations; concurrent administration of lithium and NSAIDs may result in elevated lithium serum levels leading to lithium toxicity |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Acute renal insufficiency, interstitial nephritis, hyperkalemia, hyponatremia, and renal papillary necrosis may occur; patients with preexisting renal disease or compromised renal perfusion, risk acute renal failure; leukopenia occurs rarely, is transient, and usually returns to normal during therapy; persistent leukopenia, granulocytopenia, or thrombocytopenia warrants further evaluation and may require discontinuation of drug |
NEH is typically a self-limited eruption. Continue symptomatic care as needed.
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.21
| Media file 1: Courtesy of Jeffrey P. Callen, MD. | |
 | View Full Size Image | Media type: Photo |
| Media file 2: Neutrophilic infiltrate on hematoxylin and eosin stain (100X). Courtesy of Jeffrey P. Callen, MD, and Vilma Fabre, MD. | |
 | View Full Size Image | Media type: Photo |
Neutrophilic Eccrine Hidradenitis excerpt
Article Last Updated: May 2, 2008
