Neutrophilic eccrine hidradenitis
Encyclopedia
Neutrophilic eccrine hidradenitis (NEH) usually is a cutaneous complication of chemotherapy
, but it also can occur because of other reasons. It consist of fever and non specific skin lesions. It is rare, and self-limited.
, especially leukaemia, who receive chemotherapy with a cytotoxic drug. These include: Bleomycin
, chlorambucil
, cyclophosphamide
, cytarabine
, doxorubicin
, lomustine
, mitoxantrone
, topotecan
, and vincristine
.
NEH was first described in 1982 in a patient with acute myeloid leukaemia (AML) who had received cytarabine as chemotherapy.
Cancer itself, infections, and other medicinal drugs also can lead to NEH. NEH has been reported in patients with cancer who have not received any form of chemotherapy (i.e., as a paraneoplastic syndrome
), in patients with HIV
and/or AIDS
, and after the use of paracetamol
(acetaminophen). Also the use of targeted agents can lead to NEH, e.g. imatinib
, a tyrosine kinase inhibitor.
NEH has also been described without any known reason (idiopathic
cases), including idiopathic cases in children.
) and swelling (oedema) of the skin – are the commonest symptoms of NEH. Patients usually present with the skin eruption 1-2 weeks after use of the cytotoxic drug. Sometimes, the skin eruption can be painful. Skin eruptions can be located on the extremities, trunk, and face. Severe lesions are rare, and can mimic cellulitis
. Generalised lesions resembling erythema multiforme
have been reported.
In NEH, eccrine gland necrosis
, and neutrophils surroundings the eccrine glands, are typical findings on biopsy. If the chemotherapy has recently been administered, chemotherapy induced neutropenia
may be present, and, as a result, the neutrophils may be absent. But the other characteristic finding, i.e. eccrine gland necrosis, can still be seen. A vacuolar interface dermatitis
also is visible in glands and ducts, along with necrosis of the lining cells.
In addition, in patients receiving chemotherapy, keratinocyte atypia can be seen.
However, if the patient developed NEH after chemotherapy, the offending cytotoxic drug has to be discontinued, and the patient must avoid this particular cytotoxic drug in the future, because NEH usually re occurs upon re exposure to the same cytotoxic drug.
Despite the fact that NEH is self limited and usually resolves without treatment, some researchers use treatment, mainly systemic corticosteroids, although the efficacy of such a therapy has not been demonstrated in a large randomised controlled clinical trial until now.
may be useful for prevention. However, the efficacy of oral dapsone as prevention has not been demonstrated very clearly until now.
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
, but it also can occur because of other reasons. It consist of fever and non specific skin lesions. It is rare, and self-limited.
What can lead to NEH
The overwhelming majority of neutrophilic eccrine hidradenitis (NEH) is seen in patients with cancerCancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
, especially leukaemia, who receive chemotherapy with a cytotoxic drug. These include: Bleomycin
Bleomycin
Bleomycin is a glycopeptide antibiotic produced by the bacterium Streptomyces verticillus. Bleomycin refers to a family of structurally related compounds. When used as an anticancer agent, the chemotherapeutical forms are primarily bleomycin A2 and B2. It works by causing breaks in DNA...
, chlorambucil
Chlorambucil
Chlorambucil is a chemotherapy drug that has been mainly used in the treatment of chronic lymphocytic leukemia...
, cyclophosphamide
Cyclophosphamide
Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
, cytarabine
Cytarabine
Cytarabine, or cytosine arabinoside, is a chemotherapy agent used mainly in the treatment of cancers of white blood cells such as acute myeloid leukemia and non-Hodgkin lymphoma. It is also known as Ara-C...
, doxorubicin
Doxorubicin
Doxorubicin INN is a drug used in cancer chemotherapy. It is an anthracycline antibiotic, closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA....
, lomustine
Lomustine
Lomustine is an alkylating nitrosourea compound used in chemotherapy. It is in the same family as streptozotocin. This is a highly lipid soluble drug, and thus crosses the blood brain barrier. This property makes it ideal for treating brain tumors, and is its primary use...
, mitoxantrone
Mitoxantrone
Mitoxantrone is an anthracenedione antineoplastic agent.-Uses:It is used in the treatment of certain types of cancer, mostly metastatic breast cancer, acute myeloid leukemia, and non-Hodgkin's lymphoma...
, topotecan
Topotecan
Topotecan hydrochloride is a chemotherapy agent that is a topoisomerase I inhibitor. It is the water-soluble derivative of camptothecin...
, and vincristine
Vincristine
Vincristine , formally known as leurocristine, sometimes abbreviated "VCR", is a vinca alkaloid from the Catharanthus roseus , formerly Vinca rosea and hence its name. It is a mitotic inhibitor, and is used in cancer chemotherapy.-Mechanism:Tubulin is a structural protein that polymerizes to...
.
NEH was first described in 1982 in a patient with acute myeloid leukaemia (AML) who had received cytarabine as chemotherapy.
Cancer itself, infections, and other medicinal drugs also can lead to NEH. NEH has been reported in patients with cancer who have not received any form of chemotherapy (i.e., as a paraneoplastic syndrome
Paraneoplastic syndrome
A paraneoplastic syndrome is a disease or symptom that is the consequence of the presence of cancer in the body, but is not due to the local presence of cancer cells. These phenomena are mediated by humoral factors excreted by tumor cells or by an immune response against the tumor...
), in patients with HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
and/or AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
, and after the use of paracetamol
Paracetamol
Paracetamol INN , or acetaminophen USAN , is a widely used over-the-counter analgesic and antipyretic . It is commonly used for the relief of headaches and other minor aches and pains and is a major ingredient in numerous cold and flu remedies...
(acetaminophen). Also the use of targeted agents can lead to NEH, e.g. imatinib
Imatinib
Imatinib is a drug used to treat certain types of cancer. It is currently marketed by Novartis as Gleevec or Glivec as its mesylate salt, imatinib mesilate . It is used in treating chronic myelogenous leukemia , gastrointestinal stromal tumors and some other diseases...
, a tyrosine kinase inhibitor.
NEH has also been described without any known reason (idiopathic
Idiopathic
Idiopathic is an adjective used primarily in medicine meaning arising spontaneously or from an obscure or unknown cause. From Greek ἴδιος, idios + πάθος, pathos , it means approximately "a disease of its own kind". It is technically a term from nosology, the classification of disease...
cases), including idiopathic cases in children.
Cause
The exact cause of NEH is unknown. In patients receiving chemotherapy, it has been postulated that a high concentration of the cytotoxic drug in sweat has a direct toxic effect on the eccrine glands.Symptoms
Fever and a non specific skin eruption – with reddening (erythemaErythema
Erythema is redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin. It occurs with any skin injury, infection, or inflammation...
) and swelling (oedema) of the skin – are the commonest symptoms of NEH. Patients usually present with the skin eruption 1-2 weeks after use of the cytotoxic drug. Sometimes, the skin eruption can be painful. Skin eruptions can be located on the extremities, trunk, and face. Severe lesions are rare, and can mimic cellulitis
Cellulitis
Cellulitis is a diffuse inflammation of connective tissue with severe inflammation of dermal and subcutaneous layers of the skin. Cellulitis can be caused by normal skin flora or by exogenous bacteria, and often occurs where the skin has previously been broken: cracks in the skin, cuts, blisters,...
. Generalised lesions resembling erythema multiforme
Erythema multiforme
Erythema multiforme is a skin condition of unknown cause, possibly mediated by deposition of immune complex in the superficial microvasculature of the skin and oral mucous membrane that usually follows an infection or drug exposure...
have been reported.
Diagnosis
In all cases of suspected NEH, a skin biopsy should be performed, because the clinical symptoms are non specific, but the histopathological findings on the biopsy are specific. The biopsy shows characteristic changes of the eccrine glands, the major sweat glands of the body.In NEH, eccrine gland necrosis
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
, and neutrophils surroundings the eccrine glands, are typical findings on biopsy. If the chemotherapy has recently been administered, chemotherapy induced neutropenia
Neutropenia
Neutropenia, from Latin prefix neutro- and Greek suffix -πενία , is a granulocyte disorder characterized by an abnormally low number of neutrophils, the most important type of white blood cell...
may be present, and, as a result, the neutrophils may be absent. But the other characteristic finding, i.e. eccrine gland necrosis, can still be seen. A vacuolar interface dermatitis
Dermatitis
-Etymology:Dermatitis derives from Greek derma "skin" + -itis "inflammation" and genetic disorder.-Terminology:There are several different types of dermatitis. The different kinds usually have in common an allergic reaction to specific allergens. The term may describe eczema, which is also called...
also is visible in glands and ducts, along with necrosis of the lining cells.
In addition, in patients receiving chemotherapy, keratinocyte atypia can be seen.
Treatment
NEH is self limited and usually resolves without treatment. In the overwhelming majority of the cases, spontaneous resolution occurs in 1-2 weeks.However, if the patient developed NEH after chemotherapy, the offending cytotoxic drug has to be discontinued, and the patient must avoid this particular cytotoxic drug in the future, because NEH usually re occurs upon re exposure to the same cytotoxic drug.
Despite the fact that NEH is self limited and usually resolves without treatment, some researchers use treatment, mainly systemic corticosteroids, although the efficacy of such a therapy has not been demonstrated in a large randomised controlled clinical trial until now.
Prevention
A single case report suggested that oral dapsoneDapsone
Dapsone is a medication most commonly used in combination with rifampicin and clofazimine as multidrug therapy for the treatment of Mycobacterium leprae infections . It is also second-line treatment for prophylaxis against Pneumocystis pneumonia caused by Pneumocystis jiroveci Dapsone...
may be useful for prevention. However, the efficacy of oral dapsone as prevention has not been demonstrated very clearly until now.