Exfoliative Dermatitis

GULIZ KAIUKAVLI. M.U.. CIRANT BECKHAM, M.D.. IDA ORENGO. M.D., and TED ROSEN, M.D.
Baylor Cxillege of Medicine, Houston, Texas

Exfoliative dermatitis, also known as etythroderma, is an uncommon but serious skin
disorder that family physicians must be able to recognize and treat appropriately.
Although the etiology is often unknown, exfoliative dermatitis may be the result of a
drug reaction or an underlying malignancy. The approach to treatment should include
discontinuation of any potentially causative medications and a search for any underlying malignancy. One of the most common malignancies associated with exfoliative
dermatitis is cutaneous T-cell lymphoma, which may not manifest for months or even
years after the onset of the skin condition. Hospitalization is usually necessary for initial evaluation and treatment. In the hospital, special attention must be given to maintaining temperature control, replacing lost fluids and electrolytes, and preventing and
treating infection. The long-term prognosis is good in patients with drug-induced disease, although the course tends to be remitting and relapsing in idiopathic cases. The
prognosis of cases associated with malignancy typically depends on the outcome of
the underlying malignancy.

E

xfoliative dermatitis is a disease
process in which most, and sometimes all, of the skin is involved in
erythematous inflammation resulting in massive scaling.' A
variety of diseases and other exogenous factors may cause exfoliative dermatitis. Unfortunately, the clinical picture does not contribute to an understanding of the underlying
cause. Therefore, it is important to identify
and treat any underlying disease whenever
possible and to remove any contributing
external factors.-^
Incidence

Most published studies of exfoliative dermatitis have been retrospective and thus do
not address the issue of overall incidence.
Exfoliative dermatitis accounts for about 1
percent of all hospital admissions for dermatologic conditions.'
Although the disease affects both men and
women, it is more common in men, with an
average male-to-female ratio of 2.3:1. The

Known causes of exfoliative dermatitis include preexisting
dermatoses, drug reactions and malignancies.

FEBRUARY 1, 1999 / VOLUME 59, NUMBER 3

average age at onset is 55 years, although exfoliative dermatitis may occur at any time.^
Pathogenesis

Exfoliative dermatitis is the result of a dramatic increase in the epidermal turnover rate.
In patients with this disorder, the mitotic rate
and the absolute number of germinative skin
cells are higher than normal. Moreover, the
time necessary for cells to mature and travel
through the epidermis is decreased. This compressed maturation process results in an overall greater loss of epidermal material, which is
manifested clinically as severe scaling and shedding. Normal epidermis undergoes some extbliation every day, but the scales that are lost
contain little, if any, important viable material,
such as nucleic acids, soluble proteins and
amino acids.** In exfoliative dermatitis, however, protein and folate losses may be high.^
The pathogenesis of exfoliative dermatitis is
a matter of debate. In recent years, clinicians
have come to believe that this condition is secondary to a complicated interaction of cytokines and cellular adhesion molecules. Interleukin (IL)-l, IL-2, IL-8, intercellular adhesion
molecule 1 (ICAM-1), tumor necrosis factor
and interferon gamma are the cytokines that
may have roles in the pathogenensis of exfoliative dermatitis.^

AMERICAN FAMILY PHYSICIAN

625

Studies indicate that mycosis fimgoides may cause 25 to 40 percent of all cases of malignancy-related VOLUME 59. PRIMARY DERMATOLOGIC DISORDERS Dermatologic disorders occasionally present as exfotiative dermatitis. can produce erythroderma. Address correspondence to Ida Orengo. He received a medical degree and served a residency in internal medicine at Baylor College of Medicine.. Karakayli received a medical degree in Turkey. tions. antibiarthralgias. If cutaneous drug may cause exfoliative dermatitis. is a physician at Baylor Senior Health. is a professor at the Baylor College of Medicine. medications have heen known to be important causative agents. Reticuloendotheliai neoplasms. Antiepileptic medicaA pseudolymphoma reaction with fever. GRANT BECKHAM.^' The Authors GULIZ KARAKAYLl. He received a medical degree from the University of Michigan Medical Schooi. hepatosplenootics. The most notable member of this group is mycosis fungoides.Etiology The most common causes of exfoliative dermatitis are preexisting dermatoses.. anemia and erythroderma may of topical agents (Table 2f'^-*-''^ can cause develop as a result of hypersensitivity to dapexfoliative dermatitis. M. Ann Arbor. One Baylor f^aza.D. Hence. Therepathology also mimics cutaneous T-cell lymfore. where she received a medical degree and served a residency in dermatology. fymphadenopathy. M. many new drugs. JX 77030. IDA ORENGO.D.. and served a residency in dermatology at Bayiof College of Medicine. a drug-induced skin condition from exfoliative dermatitis associated with a malignancy.. with the former being the more predominant cause. 626 AMKHICAN FAMILY PHYSICIAN MALIGNANCIES Malignancies are a major cause of exfoliative dermatitis. Dallas. The most common of these are psoriasis. the clinician should always consider phoma. M.. contact dermatitis and pityriasis rubra pilaris. any sone or antiepileptic drugs. drug reactions. it can be very difficult to differentiate drugs as a possible cause. lichenoid or urticarial rashes may progress to generalized exfoliative dermatitis. Houston. 3 and 6 thrxjugh 8.'•'•'->' MEDICATIONS TABLE 1 Dermatoses Associated with Erythroderma Atopic dermatitis Candidiasis Contact dermatitis Dermatophytosis Ichthyosts Lichen planus Mastocytosis Nummular eaema Pemphigus Photosensitive eczema Pityriasis rubra pilarts Prurigo Psoriasis Reiter's syndrome Scabies Seborrheic dermatitis Staphylococcus scalded skin syndrome Stasis with autoeczematization Subacute cutaneous lupus erythematosus Vitamin deficiency Since the earliest descriptions of exfoliative dermatitis. seborrheic dermatitis. M. antihypertensive medications. Other dermatoses associated with erythroderma are listed in Table }. is 3 visiting professor at the Baylor College of Medicine. M. is an associate professor at the Baylor College of Medicine. malignancies and other misceUaneous or idiopathic disorders. Dr. Reprints are not available from the authors. 1999 . NUMBER 3 / FEBRUARY 1. calcium channel blockers and a variety megaly. but theoretically.D. the apparent increase in cases of exfoliative dermatitis may be related to the introduction of Information from reference 2. TED ROSEN. as well as internal visceral malignancies. The cutaneous T-cell lymphomas are the lymphomas most commonly associated with exfoliative dermatitis. Houston.D.D. Department of Dermatology. atopic dermatitis. F840. Drug eruptions that initially present as morbilliform.

Exfoliative Dermatitis erythroderma. 1999 / VOLUME 59. Patients with carcinoma of the colon. The relative risk of leukemia inducing erythroderma is highly variable. carcinomas of the fallopian tube. also in Bactrim. Septra) Tolbutamide (Orinase) Vancomycin (Vancocin) Information from references 2. S^zary syndrome. the leukemic variant of mycosis fungoides. Nydraztd. lung. Immunophenotypic studies with the use of advanced antibody panels may be useful in the differential diagnosis of these two forms.S. AMERICAN FAMILY PHYSICIAN 627 . Sorbitrate) Isotretinoin (Accutane) Lithium (Eskalith. Vectrin) Mitomycin-C (Mutamycin) Neomycin (Neosporin) Nitrofurantoin (Furadantin. Minodn. Betaseron) Iodine (Pima syrup) Isoniazid (Laniazid. NUMBER 3 association with hepatitis. The time interval between the appearance of exfoliative dermatitis and the appearance of cutaneous T-cell lymphoma lesions can vary from months to years or even decades.'" Reticulum cell sarcoma is another form of cutaneous T-cell lymphoma that may cause exfoliative dermatitis. Bricanyl) Tetrachloroethylene Tetracyclines Thalidomide (Synovir) Thiazide diuretics Trimethoprim (Trimpex. Rimactane) Isosorbide dinitrate (Isordil. 3 and 6 through 9. or it may precede the appearance of the cutaneous T-cell lymphoma lesion. Lithobid) Mefloquine (Larium) Mephyntoin (Mesantoin) Mercurials Mercury Mexilitene (MexittI) Minocycline (Dynacin. exfoliative dermatitis becomes the presenting sign of the underlying malignancy.^'^"''' In reviews of erythroderma. Alferon N) Interferon beta (Avonex. congenital immunodeficiency syndrome (Omenn's syndrome) and graft-versus-host disease. also in Rifamate) Streptomycin Sulfadiazine Sulfonamides Sulfonylureas Terbutaline (Brethine. Exfoliative dermatitis has been reported in FEBRUARY 1. More recently. progressive debilitation of the patient. Macrodantin) Omeprazoie (Prilosec) Para-amino salicylic add (Sodium PA. Bellatal) Phenytoin (Dilantin) Quinacrine Quinidine (Quinidex) Ranttidine {Zantac} Rifampin (Rifadin." Internal (visceral) malignancies cause about 1 percent of all cases of exfoliative dermatitis. acquired immunodeficiency syndrome.' ' Frequently.*'' The erythroderma may arise as a progression from a previous cutaneous Tcell lymphoma lesion or appear simultaneously with the cutaneous T-cell lymphoma.^" OTHER ASSOCIATED DISORDERS Erythroderma is also associated with disorders that cannot easily be classified into groups. TABLE 2 Drugs Associated with Erythroderma Acetaminophen Actinomycin D (Cosmegan) Allopurind (Zyloprim) Aminoglycosides Aminophylline Amiodarone (Cordarone) Arsenic Aztreonam (Azactam) Barbiturates Calcium channel blockers Captopril (Capoten) Carbamazepine (Tegretol) Cephabsporins Chinese herbs Chloroquine (Aralen) Chlorothiazide (Diuril) Chlorpromazine (Thorazine) Chlorpropamide (Diabinese) Cimetidine (Tagamet) Cisplatin (Platinol) Clofazimine (Lamprene) Clotrimazole (Lotritnin) Codeine Cyclobenzaprine (Flexeril) Dapsone Dimercaprol (BAL in Oil) Ethylenediamines Gold Hydantoins Hydroxychloroquine (Plaquenil) lnter!eukin-2 (Proleukin) Interferon alfa {Roferon-A. Modane) Phenothiazines Phenobarbital (Donnatal. ranging from 11 to 50 percent. erythroderma is the presenting sign of the malignancy.'^ larynx'^ and esophagus''' have been reported as causes of exfoliative dermatitis. also in Rifamate. absence of previous skin disease and resistance to standard therapy are features that may suggest an underlying malignancy. Rimactane. prostate and thyroid have presented with erythroderma. Alophen. The erythrodermic form of mycosis fungoides and the S^zary syndrome may also be difficult to distinguish from benign erythroderma. Acute and chronic leukemia may also cause exfoliative dermatitis.) Penicillins Phenolphthalein (Agoral. a significant percentage of patients (about 25 percent) do not receive a specific etiologic diagnosis. Intron A. When it precedes cutaneous T-cell lymphoma lesions. Insidious development of the erythroderma. is also associated with exfoliative dermatitis.

whereas chronic processes produce smaller ones. Other clinical findings include lymphadenopathy. decreased sensitivity to the shivering reflex and extra cooling that comesfromevaporation of the fluids leaking out of the weeping skin lesions all result in thermoregulatory dysfunction that can cause hypothermia or hyperthermia. Hypothermia can result in ventricular flutter. Both hyperthermia and hypothermia are reported. and renders itself much more vulnerable to infection. Acute processes usually favor large scales. The exfoliative process also may involve the scalp. Since cutaneous fijnction as a multiprotective barrier is so dis- 628 AMERICAN FANHLY PHYSICIAN FIGURE 1. water. Loss of normal vasoconstriaive function in the dermis. protein and electrolytes.* CLINICAL MANIFESTATIONS Clinically. the palms of the hands. A catabolic state thus ensues.Erythematous. which Is often responsible for significant weight loss. rupted in exfoliative dermatitis. the first stage of exfoliative dermatitis is erythema. such as hyperkeratosis. Each of these physiologic disruptions is potentially life-threatening. In some studies. parakerato- VOLUME 59. pruritic patches tend to spread over a period of days to weeks and are followed by scaling. Elderly man with exfoliative dermatitis of the face caused by psoriasis. skin biopsies show nonspecific histopathologic features. A significant number of these patients eventually progress to cutaneous T-ceU lymphoma. These patches tend to spread until. often begimiing as single or multiple pruritic patches. decreased heart rate and hypotension.** The basal metabolic rate also is increased in patients with exfoliative dermatitis.^ Nails can often become dystrophic. but not always. This has been called the "nose sign.'"-" Heat loss is another major concern that accompanies a defective skin barrier in patients with exfoliative dermatitis.1999 . pruritic eruption. Some of these patients undergo spontaneous resolution. trunk and genital region. The scales may be small or large. after a matter of days or weeks.'** The scaling that occurs in exfoliative dermatitis can have severe metabolic consequences. depending on the intensity and the duration of the scaling. pruritis and a chilly sensation. superficial or deep. splenomegaly. particularly in patients with preexisting psoriasis. the body loses heat. edema of the foot or ankle^* and gynecomastia. Usually. Hypervolemia can also occur in patients with exfoUative dermatitis."'* Once the erythema is well established. most of the skin surface is covered witli an erythematous. involving especially the head. contributing to the likelihood of cardiac HISTOPATHOLOGY In most patients with erythroderma. the soles of the feet and the mucous membranes are spared. NUMBER 3 / FEBRUARY 1. Other cases are ultimately classifiable as another dermatosis. hepatomegaly. with 25 percent of patients developing alopecia. scaling inevitably follows {Figure I). Exfoliative dermatitis is also a risk factor for epidemic spread of methicillin-resistant Staphylococcus aureus.^'*' The most fi-equently noted symptoms in patients with exfoliative dermatitis include malaise. the nose and paranasal area are spared. Increased peripheral blood flow can result in high-output cardiac failure.

elevated erythrocyte sedimentation rate. such as methotrexate (Rheumatrex) and azathioprine (Imuran)."'^^ When used as adjunctive therapy. Druginduced exfoliative dermatitis is usually short-lived once the inciting medication is withdrawn and appropriate therapy is administered. Patients who have exfoliative dermatitis of unknown cause tend to have an unpredictable course. The clinical course of patients with malignancies depends on the type of malignancy and the response to appropriate therapy. laboratory and radiologic investigations and monitoring are performed. usually replete with multiple remissions and exacerbations. Even patients with clear histories of preexisting dermatoses tend to have biopsies that are not diagnostic when they present with erythroderma/ Laboratory Findings Lahoratory evaluation of patients with erythroderma is generally not very helpful in determining a specific diagnosis. leukocytosis. acanthosis and a chronic perivascular inflammatory infiltrate. behavior modification designed to eliminate persistent scratching has been successfiil in reducing the rate of excoriation and increasing the rate of healing. fluid and electrolyte abnormalities. Typical laboratory values include mild anemia. before determination of the etiology.'-'"" Blood counts and bone marrow studies may reveal an underlying leukemia. pulmonary or systemic. Treatment Hospitalization and dermatologic consultation are indicated in most cases to ensure that all of the necessary cutaneous. Prognosis and Sequelae Even though exfoliative dermatitis is a complex disorder involving many factors.Exfoliative Dermatitis sis. but only if the cells are identified in unequivocally large numbers. total-body electron beam irradiation. the underlying disease is usually the key determinant of the course and prognosis. Consultation with an oncologist who is well-versed in treatment of cutaneous T-cell lymphoma is advisable once the disease progresses to the tumor stage. The balance of fluids and electrolytes should be closely monitored. or immunosuppressive agents FEBRUARY 1. Analysis for circulating Sezary cells may he helpful. the rate of mortality AMERICAN FAMII Y PHYSICIAN 629 . but clearing almost always occurs eventually. These measures include bed rest.^^^' In patients with chronic idiopathic erythroderma. emollients and topical steroids may be effective.. Also. systemic steroids (if psoriasis has been ruled out). Clinical Course. In the acute phase. whether cutaneous. bland emollients and oral antihistamines. systemic chemotherapy and extracorporeal photopheresis. Options include use of PUVA light therapy. eosinophilia. Patients with underlying skin disorders may respond much more slowly to therapy.e. NUMBER 3 Acute treatment should be aimed at soothing the inflamed skin with bed rest. cardiac failure). since dehydration or hypervolemia can be problems. lukewarm soaks. abnormal serum protein electrophoresis with a polyclonal elevation in the gamma globulin region. treatment consists of measures to soothe the inflamed skin. with or without eosinophils.* In patients who develop complications (i. and elevated igE levels. infection. 1999 / VOLUME 59. bland emollients and oral antihistamines. retinoids (for exfoliative dermatitis secondary to psoriasis and pityriasis rubra pilaris). physicians should be vigilant about possible secondary infection. Other patients may warrant PUVA (psoralen plus ultraviolet A) phototherapy. lukewarm soaks or baths. topical nitrogen mustard.^" No uniformity of opinion exists concerning the best treatment for cutaneous T-cell lymphoma.

18:189. The most common causes of death in patients with exfoliative dermatitis are pneumonia.In. Wolff K. 24. Philadelphia: Saunders. Lowenthal RM. 4. Herbold DR. Erythroderma and exfoliative dermatitis. Arch Dermatol 1963. Faure M. Helwig EB. Mycosis fungoides-like lesions associated with phenytoin therapy Arch Dermatol 1985. 18. Exfoliative dermatitis. et al. Dermatitis exfoliativa. Mauduit G. Exfoliative dermatitis. Transfusion-associated graft-versus-host disease: report of an occurrence following the administration of irradiated blood. Hurley HJ. Gibson LE.13(2Pt 1):311*2. In: Maddin S. Br Med J 1967. 7. 2d ed.167 42-6. Exfoliative dermatitis as a risk factor for epidemic spread of methicillin resistant Staphylococcus aureus Iletterl. eds. Schwartz RA. Goldblum RM. Acta Derm Venereol 1958. Overton-Keary PR Goette DK. Eisen AZ. 17. Wilkinson P. Grice KA. 10.Exfoliative dermatitis of unknown etiology: a description and follow-up of 38 patients. Brown TH. Disseminated pyogenic granuloma developing after an exfoliative dermatitis J Am Acad Dermatol 1995. eds. Advanced dermatologic therapy. 30. Exfoliative dermatitis: presenting sign of internal malignancy. Arch Intern Med 1969. Bills P. Kahane E. Sanchez JL. 5. Carruthers A. Thestrup-Pedersen K. Wirt DP. Generalized vitiligo after erythroderma. 3. Benign and malignant forms of erythroderma: cutaneous immunophenotypic characteristics. Parkin WG. Russo DC. ThivoletJ. Brown JB. 11. Nicolis GD.32(2 Pt l):280-2. The red man syndrome. 3d ed. 23. Challis DR.UMF-59.is often higb. Torres JE. Dermalologica 1985:170147-51.75:344. Voi. 29. Shuster S. 2. Behavior therapy techniques in treatment of exfoliative dermatitis. Halkier-Sorensen L. Nose sign of exfoliative dermatitis: a possible mechanism (Letter]. eds. Vossbeck S. Trotter MG. Cardiovascular. 14. et al. diffuse areas of postinflammatory hyperpigmentation and hypopigmentation may occur.n6:919-22. Jester JO. 21. Philadelphia: Saunders. 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