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Background
This is a rare and unusual complication of chemotherapy and has been associated with numerous underlying diseases including malignancies. These lesions present with erythematous plaques, usually on the palmar surfaces. However, numerous unusual locations have been identified. Clinically, these lesions may raise the suspicion of an underlying infection and leads to biopsy and culture of the lesions. The characteristic histopathology combined with the clinical setting leads to the correct diagnosis.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS Chemotherapy-associated eccrine hidradenitis INCIDENCE Rare AGE RANGE-MEDIAN All age groups All
DISEASE ASSOCIATIONS CHARACTERIZATION GENERAL Neutrophilic eccrine hidradenitis in the absence of an underlying malignancy.
Kuttner BJ, Kurban RS.
Department of Pathology, New York Hospital-Cornell Medical Center, New York 10021.
Cutis 1988 Jun;41(6):403-5 Abstract quote
Neutrophilic eccrine hidradenitis is an entity previously reported to occur in association with malignancy and chemotherapy.
We report a case of clinical and histopathologic findings characteristic of neutrophilic eccrine hidradenitis occurring without apparent underlying disease. In addition, the only medication this patient was taking was acetaminophen. Neutrophilic eccrine hidradenitis appears to represent a reaction pattern without specificity for underlying disease or inciting agent.
BEHCET'S DISEASE Neutrophilic eccrine hidradenitis in a patient with Behcet's disease.
Bilic M, Mutasim DF.
University of Cincinnati College of Medicine, Ohio, USA.
Cutis 2001 Aug;68(2):107-11 Abstract quote
Patients with Behcet's disease may develop multiple mucocutaneous manifestations, several of which are mediated by neutrophils. These include aphthous ulcers, pseudofolliculitis, acneform lesions, and pathergy.
We report another neutrophil-mediated disorder, neutrophilic eccrine hidradenitis (NEH), in a patient with Behcet's disease. NEH should be added to the list of mucocutaneous lesions that may be seen in patients with Behcet's disease.
CHEMOTHERAPY Neutrophilic eccrine hidradenitis associated with induction chemotherapy.
Fitzpatrick JE, Bennion SD, Reed OM, Wilson T, Reddy VV, Golitz L.
Service of Dermatology, Fitzsimons Army Medical Center, Aurora, CO 80045-6000.
J Cutan Pathol 1987 Oct;14(5):272-8 Abstract quote
We report three new cases of neutrophilic eccrine hidradenitis associated with induction chemotherapy which resolves two major points.
First, because two of our patients had testicular carcinoma; this firmly establishes that NEH is not exclusively seen in patients with acute myelogenous leukemia or Hodgkin's lymphoma as previously reported.
Second, because two of our patients did not receive cytarabine which has previously been suspected of being the causative agent, it is apparent that this disorder may be produced by more than one chemotherapeutic agent or combination of agents.
The histologic features with a discussion of the spectrum of changes which may be seen are presented.
GCSF Neutrophilic eccrine hidradenitis induced by granulocyte colony-stimulating factor.
Bachmeyer C, Chaibi P, Aractingi S.
Br J Dermatol 1998 Aug;139(2):354-5 HIV-1 Neutrophil eccrine hidradenitis in a patient with AIDS.
Krischer J, Rutschmann O, Roten SV, Harms M, Saurat JH, Pechere M.
Clinic of Dermatology, University Hospital Geneva, Switzerland.
J Dermatol 1998 Mar;25(3):199-200 Abstract quote
Neutrophilic eccrine hidradenitis (NEH), first described as a rare, transient, and benign complication of various chemotherapy regimens for acute leukemia, has also been observed in other conditions, including three HIV-positive patients and even in otherwise healthy individuals.
A similar histological pattern was described after intradermal bleomycin injections into normal human skin.
We report the first case of NEH in a hemophilic HIV infected patient treated with stavudine, a new reverse transcriptase inhibitor.
Recurrent neutrophilic eccrine hidradenitis in an HIV-1-infected patient.
Bachmeyer C, Reygagne P, Aractingi S.
Unite de Dermatologie, Hopital Tenon, Paris, France.
Dermatology 2000;200(4):328-30 Abstract quote
Most cases of neutrophilic eccrine hidradenitis (NEH) have been reported in patients receiving chemotherapy for acute myelogenous leukemia or other malignant diseases.
We report the case of an HIV-1-infected patient who presented several and strikingly similar episodes of NEH without any medication as well as another one after the first course of chemotherapy for a B-cell non-Hodgkin's lymphoma.
This case strengthens the hypothesis that NEH may occur in different situations, as reported for other neutrophilic dermatoses.
HODGKIN'S DISEASE Neutrophilic eccrine hidradenitis associated with Hodgkin's disease and chemotherapy. A case report.
Beutner KR, Packman CH, Markowitch W.
Arch Dermatol 1986 Jul;122(7):809-11 Abstract quote
A 44-year-old man with Hodgkin's disease developed fever and erythematous macules and plaques associated with doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy.
Biopsy results demonstrated a neutrophilic infiltrate around sweat glands and degeneration of eccrine glands. These findings are characteristic of neutrophilic eccrine hidradenitis, which, to our knowledge, has previously been reported only in patients with acute myelogenous leukemia who were receiving cytarabine chemotherapy.
Neutrophilic eccrine hidradenitis may represent a reaction pattern to chemotherapeutic agents and may not be specific for a particular disease or drug.
NEUTROPENIA Neutrophilic eccrine hidradenitis in two neutropenic patients.
Allegue F, Soria C, Rocamora A, Munoz E, Freire-Murgueytio P, Arrazola JM, Ledo A.
Department of Dermatology, Hospital Ramon y Cajal, Madrid, Spain.
J Am Acad Dermatol 1990 Dec;23(6 Pt 1):1110-3 Abstract quote
Neutrophilic eccrine hidradenitis is an uncommon, self-limited dermatosis with a variable clinical presentation. It seems to be due to chemotherapeutic drugs in most cases. Necrosis of the eccrine gland associated with a neutrophilic infiltrate is the histologic hallmark of this disease.
We report two additional cases in neutropenic patients with acute myelogenous leukemia in which there was a striking lack of neutrophil infiltration. A new term, drug-associated eccrine hidradenitis, is suggested.
Neutrophilic eccrine hidradenitis in two neutropaenic patients.
Keane FM, Munn SE, Buckley DA, Hopster D, Mufti GJ, du Vivier AW.
Department of Dermatology, King's College Hospital, London, UK.
Clin Exp Dermatol 2001 Mar;26(2):162-5 Abstract quote
We describe two patients, who presented with erythematous facial plaques, in keeping with neutrophilic eccrine hidradenitis, during chemotherapy for acute myeloid leukaemia. Both patients were neutropaenic and febrile.
Histology showed a dermal neutrophilic infiltrate around the eccrine glands with gland destruction.
The importance of recognizing this disorder is to prevent the inappropriate use of antibiotics as it is self limiting.
SERRATIA MARCESCENS Neutrophilic eccrine hidradenitis secondary to infection with Serratia marcescens.
Combemale P, Faisant M, Azoulay-Petit C, Dupin M, Kanitakis J.
Department of Dermatology, Instruction Military Hospital 'Desgenettes', 108 boulevard Pinel, 69003 Lyon, France.
Br J Dermatol 2000 Apr;142(4):784-8 Abstract quote
Neutrophilic eccrine hidradenitis (NEH) is a rare dermatosis which usually develops after administration of chemotherapeutic treatments. An infective origin is exceptional.
We report a patient, previously operated on for ependymoma, who presented with an eruption typical of NEH even though he had not received chemotherapy. Culture of a skin biopsy revealed Serratia marcescens. The dermatosis improved after antibiotic therapy but recurred twice and culture again isolated S. marcescens; electron microscopy revealed cytoplasmic inclusions within neutrophils, suggestive of bacteria. The disease improved every time with appropriate antibiotic therapy. An infective aetiology for NEH is rare: three such cases have been reported, of which one was due to S. marcescens. The originality of our case is the recurrence of the disease on three occasions with the same bacterium isolated on each occasion, with disease remission after antibiotic therapy.
This case confirms that infections may be a possible cause of NEH and underlines the necessity to search for infective agents, especially in patients immunocompromised by haematopoietic malignancies and/or chemotherapeutic treatments.
PATHOGENESIS CHARACTERIZATION TOXIN Thought to be a direct toxic effect of chemotherapy agents upon the eccrine epithelium Chemotherapy-associated eccrine hidradenitis: neutrophilic eccrine hidradenitis reevaluated: the role of neutrophilic infiltration.
Greenbaum BH, Heymann WR, Reid CS, Travis SF, Donaldson MH.
Division of Hematology/Oncology, Robert Wood Johnson School of Medicine, Camden, New Jersey.
Med Pediatr Oncol 1988;16(5):351-5 Abstract quote
Two cases of chemotherapy-associated eccrine hidradenitis are presented. Previous cases have been labeled "neutrophilic eccrine hidradenitis" (NEH). Both cases reported herein involve neutropenic patients and are notable for the absence of neutrophils on histologic examination.
Oncologists need to be aware of this newly described process, and this rash must be added to the differential diagnosis of the neutropenic oncology patient. The role of neutrophils in this disorder is discussed, and a new term, "chemotherapy-associated eccrine hidradenitis," is suggested for this unusual process.
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION GENERAL Neutrophilic eccrine hidradenitis: a distinctive rash associated with cytarabine therapy and acute leukemia.
Flynn TC, Harrist TJ, Murphy GF, Loss RW, Moschella SL.
J Am Acad Dermatol 1984 Oct;11(4 Pt 1):584-90 Abstract quote
Neutrophilic eccrine hidradenitis (NEH) is a recently described neutrophilic dermatosis associated with acute myelogenous leukemia (AML) and chemotherapy. This disorder is a distinct clinicopathologic entity separate from leukemid reactions and other neutrophilic dermatoses.
We describe two cases in which plaques or nodules developed in the second week after initiation of induction chemotherapy for AML. The lesions regressed in 1 week and recurred in one case when induction chemotherapy was given a second time.
Histologically, the findings were similar in each case. Neutrophils palisaded about and infiltrated the eccrine coil in which necrosis of secretory epithelium was present. Focal mucinous degeneration of the eccrine adipose tissue cuff was the only other significant alteration. No vasculitis was observed. Cultures and histologic preparations for pathogenic organisms were negative. Cytarabine was the chemotherapeutic agent used in all three cases. NEH most likely represents either an unusual response caused by cytarabine or a manifestation of AML.
Recognition of NEH is important in order to exclude other neutrophilic dermatoses associated with AML, such as sepsis and leukemia cutis, which may appear clinically similar.
VARIANTS EARS Neutrophilic eccrine hidradenitis with an unusual presentation.
Ostlere LS, Wells J, Stevens HP, Prentice G, Rustin MH.
Department of Dermatology, Royal Free Hospital and School of Medicine, London, U.K.
Br J Dermatol 1993 Jun;128(6):696-8 Abstract quote
Neutrophilic eccrine hidradenitis (NEH) is an eruption most commonly seen in patients undergoing chemotherapy, and is characterized histologically by a neutrophilic infiltrate around the eccrine coils, with associated necrosis of the sweat coils. The rash usually affects the trunk and extremities, and the morphology of the lesions is very variable.
We describe a patient with neutrophilic eccrine hidradenitis who presented with symmetrical, erythematous, swollen ears, a manifestation of NEH which has not been previously reported.
JUVENILE VARIANT Juvenile neutrophilic eccrine hidradenitis: a vasculitis-like plantar dermatosis.
Drake M, Sanchez-Burson JM, Dona-Naranjo MA, Conde JM.
Section of Rheumatology, Valme University Hospital, Seville, Spain.
Clin Rheumatol 2000;19(6):481-3 Abstract quote
Neutrophilic eccrine hidradenitis is a variety of neutrophilic dermatosis described in patients with different neoplasms, most often leukaemia, and different chemotherapy regimens. It is characterised by neutrophilic infiltration of the eccrine coils of sweat glands. Recently it has been described in healthy juveniles, involving primarily the soles of the feet.
We describe five new cases of juvenile neutrophilic eccrine hidradenitis all showing a good prognosis or a self-limiting course.
PERIORBITAL CELLULITIS Neutrophilic eccrine hidradenitis simulating orbital cellulitis.
Bardenstein DS, Haluschak J, Gerson S, Zaim MT.
Department of Ophthalmology, Case Western Reserve University, Cleveland, Ohio.
Arch Ophthalmol 1994 Nov;112(11):1460-3 Abstract quote
Orbital swelling in patients with cancer can reflect neoplastic or infectious processes. Accurate diagnosis can be especially difficult in the face of associated fever and neutropenia.
We treated a 30-year-old man undergoing induction chemotherapy for acute myelogenous leukemia, who had fever of unknown origin and periorbital swelling suggestive of orbital cellulitis. However, the periorbital findings were more compatible with passive swelling and hemorrhage. A skin biopsy specimen demonstrated isolated neutrophilic inflammation and necrosis of the eccrine glands. Cultures of the tissue for bacteria and fungi were negative. Pertinent literature regarding eccrine-gland inflammatory disease was reviewed. This unusual entity, termed neutrophilic eccrine hidradenitis, is most common in patients undergoing induction chemotherapy. Cases with infectious causes and cases in neutropenic patients have also been reported.
No other patients, to our knowledge, with periocular involvement by neutrophilic eccrine hidradenitis have been described. Neutrophilic eccrine hidradenitis should be added to the differential diagnosis of cases of periocular hemorrhage and swelling in patients with cancer who receive chemotherapy.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL Neutrophilic eccrine hidradenitis. A distinctive type of neutrophilic dermatosis associated with myelogenous leukemia and chemotherapy.
Harrist TJ, Fine JD, Berman RS, Murphy GF, Mihm MC Jr.
Arch Dermatol 1982 Apr;118(4):263-6 Abstract quote
On two occasions, erythematous edematous plaques developed on the left side of the neck and the left shoulder of a man undergoing induction chemotherapy for acute myelogenous leukemia. The lesions resolved after several days in both instances.
Histologically, numerous neutrophils surrounded and focally infiltrated the eccrine secretory coils, in which epithelial necrosis was observed. The "fixed" nature of the plaques and temporal relationship to chemotherapy suggest that the lesions represent an unusual reaction to chemotherapeutic agents.
It is possible that this unique clinicopathologic picture represents a neutrophilic dermatosis associated with leukemia.
Neutrophilic hidradenitis induced by chemotherapy involves eccrine and apocrine glands.
Brehler R, Reimann S, Bonsmann G, Metze D.
Department of Dermatology, University of Munster, Germany.
Am J Dermatopathol 1997 Feb;19(1):73-8 Abstract quote
Neutrophilic eccrine hidradenitis is a self-limited inflammatory dermatosis primarily induced by chemotherapeutic agents. We report the case of a 43-year-old patient treated with cytarabine, daunorubicin, and thioguanine for acute myelogenous leukemia who developed painful, red nodules in both axillae on the third day of chemotherapy. The lesions healed spontaneously without sequelae and reappeared once when chemotherapy was readministered.
Histologic examination and immunohistochemical staining for carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), and S100 revealed necrosis of eccrine and apocrine glands. As a secondary event, neutrophils, histiocytes, and lymphocytes of T and B cell types were infiltrating the glandular coils. Electron microscopic examination confirmed the presence of severe cellular degeneration of the secretory epithelia and coiled sweat ducts. Ultrastructural features and absence of labeling with a nick-end labeling technique were consistent with a non-apoptotic mode of cell death.
Our findings strongly suggest a cytotoxic effect of chemotherapeutic agents as accumulated in the secretory epithelia of sweat glands. Distal ducts and myoepithelial cells remained intact and may account for rapid regeneration of the glandular structures after discontinuation of chemotherapy. In view of the involvement of both eccrine and apocrine glands, we suggest the term neutrophilic hidradenitis, which is part of the spectrum of drug-associated sweat gland reactions.
VARIANTS SQUAMOUS SYRINGOMETAPLASIA Eccrine squamous syringometaplasia. A cutaneous sweat gland reaction in the histologic spectrum of 'chemotherapy-associated eccrine hidradenitis' and 'neutrophilic eccrine hidradenitis'.
Hurt MA, Halvorson RD, Petr FC Jr, Cooper JT Jr, Friedman DJ.
Department of Pathology, University of Texas Health Science Center, San Antonio 78284-7750.
Arch Dermatol 1990 Jan;126(1):73-7 Abstract quote
A 31-year-old Hispanic man presented in the pancytopenic phase of acute myelocytic leukemia and was treated with the chemotherapeutic agents mitoxantrone and cytarabine.
After 5 days, an erythematous, blanching, papular, crusted eruption developed on his forehead, chest, and legs. Some lesions showed confluence and all were at the same developmental stage. Clinical diagnoses included necrotizing vasculitis and sepsis. A biopsy specimen revealed widespread noninflammatory syringometaplasia of eccrine ducts. Well-developed intercellular bridges and eosinophilic cytoplasm were seen within the metaplastic cells; apoptoses and occasional mitoses were present.
This process is distinct and probably occurred secondary to direct toxic injury from the chemotherapeutic drugs. Because similar changes have occurred in patients with neutrophilic eccrine hidradenitis, we believe our patient represents an example of the noninflammatory end of the spectrum of chemotherapeutic eccrine gland reactions.
Syringosquamous metaplasia. A distinctive eruption in patients receiving chemotherapy.
Bhawan J, Malhotra R.
Department of Dermatology, Boston University School of Medicine, Massachusetts 02118-2394.
Am J Dermatopathol 1990 Feb;12(1):1-6 Abstract quote
Squamous metaplasia of the upper portion of the sweat ducts has been observed in four patients who received chemotherapy; two patients with acute myelogenous leukemia, one patient with testicular carcinoma, and one patient with anaplastic carcinoma of the lung.
This change is different (but perhaps related) from what is described in neutrophilic eccrine hidradenitis in patients with acute myelogenous leukemia and other tumors after chemotherapy. Syringosquamous metaplasia may be confused with well differentiated squamous cell carcinoma histologically.
Chemotherapy-induced eccrine squamous syringometaplasia. A distinctive eruption in patients receiving hematopoietic progenitor cells.
Valks R, Fraga J, Porras-Luque J, Figuera A, Garcia-Diez A, Fernandez-Herrera J.
Department of Dermatology, Hospital Universitario de la Princesa, Madrid, Spain.
Arch Dermatol 1997 Jul;133(7):873-8 Abstract quote
BACKGROUND: Eccrine squamous syringometaplasia (ESS) has been associated with characteristic clinical eruption in patients receiving chemotherapy. It has been suggested as a diagnostic clue in the diagnosis of chemotherapy-induced reactions vs acute graft-vs-host disease, as well as other drug reactions. We identified 10 cases of ESS in patients in whom a distinctive clinical eruption developed during or after a pretransplantation conditioning regimen with high-dose chemotherapy. A complete clinical and histologic evaluation was performed in all patients.
OBSERVATIONS: All patients developed erythematous and edematous plaques or confluent erythematous macular areas in the axillae and/or groin, with painful areas of well-defined erythema and edema on palms and/or soles in 5 patients. Some discrete papular lesions on the trunk or extremities could also be observed in most patients. The histologic hallmark of the eruption was ESS, with a variable degree of cornification and apoptosis. A vacuolar interface dermatitis and a variable degree of cellular atypica were also consistent findings.
CONCLUSIONS: Chemotherapy-induced ESS may be associated with a distinctive clinical eruption and should be considered in the differential diagnosis of erythematous eruptions during or after a pretransplantation conditioning regimen with high-dose chemotherapy.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES BURNS Eccrine squamous syringometaplasia in the skin of children after burns.
Sommer B, Hagedorn M, Wood F, Heenan P.
Department of Dermatology, Darmstadt Hospital, Germany.
J Cutan Pathol 1998 Jan;25(1):56-8 Abstract quote
We report 3 cases of severe burns in children in which eccrine squamous syringometaplasia (ESS) was found in skin biopsies taken 10 days after the trauma occurred. Microscopic examination showed partial or total necrosis of the epidermis, focal dermal necrosis and squamous metaplasia in eccrine ducts.
These cases appear to be the first reported instances of ESS as an early consequence of severe burns.
CMV INFECTION Cytomegalovirus-induced syringosquamous metaplasia.
Chetty R, Bramdev A, Govender D.
Department of Pathology, University of Natal School of Medicine, Durban, South Africa.
Am J Dermatopathol 1999 Oct;21(5):487-90 Abstract quote
An unusual case of syringosquamous metaplasia of the eccrine ducts caused by cytomegalovirus (CMV) is presented. The patient was HIV positive and had extensive excoriation of the perineum and vulva. Biopsy revealed the presence of herpes simplex virus (HSV) inclusions in the necrotic exudate, a CMV vasculitis and extensive involvement of the eccrine ducts. In addition to containing typical CMV inclusions, the eccrine ducts showed proliferation and squamous metaplasia. Inclusions of HSV were not seen within the eccrine ducts by light microscopy or immunohistochemistry.
The extensive proliferation with accompanying squamous metaplasia superficially can resemble an infiltrating squamous carcinoma, but this was not evident to a great extent in this case.
To the best of our knowledge, our case represents the first of syringosquamous metaplasia of eccrine ducts caused by CMV infection.
NEUTROPHILIC DERMATOSIS PALMOPLANTAR HIDRADENITIS
Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.
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