Marti Jill Rothe, MD * , Megan L. Bernstein, BS, Jane M. Grant-Kels, MD Department of Dermatology, University of Connecticut Health Center, Farmington, CT 06030, USA Abstract Exfoliative erythroderma, or diffuse erythema and scaling of the skin, may be the morphologic presentation of a variety of cutaneous and systemic diseases. Establishing the diagnosis of the underlying disease is often difficult and, not uncommonly, erythroderma is classified as idiopathic. Several cases are presented to demonstrate the diversity of presentation of this disease. Laboratory findings are typically unhelpful in establishing the etiology of erythroderma. Clinical data combined with multiple skin biopsies over time are necessary. Systemic complications of erythroderma include infection, fluid and electrolyte imbalances, thermoregulatory disturbance, high output cardiac failure, and acute respiratory distress syndrome. The initial approach to the management of erythroderma of any etiology includes attention to nutrition, fluid and electrolyte replacement, and the institution of gentle local skin care measures. Oatmeal baths and wet dressings to weeping or crusted sites should be followed by application of bland emollients and low-potency topical corticosteroids. Systemic dermatologic therapy may be required to maintain improvement achieved with local measures or to control erythroderma refractory to local measures. The prognosis of erythroderma is dependent on the underlying etiology. D 2005 Published by Elsevier Inc. Introduction Exfoliative erythroderma, or diffuse erythema and scaling of the skin, may be the morphologic presentation of a variety of cutaneous and systemic diseases (Table 1). The dermatologist is faced with multiple challenges when caring for the patient with exfoliative erythroderma. Establishing the diagnosis of the underlying disease is often difficult and, not uncommonly, erythroderma is classified as idiopathic. Exfoliative erythroderma places the patient at high risk for secondary infection as well as cardiovascular and respiratory compromise. Additional risks are posed by systemic dermatologic therapy, which is often required to control the disease. The following case summaries highlight these clinical challenges. Case presentations Case 1 In March 2000, a 55-year-old man is referred for a second opinion to the university for a 1-year history of abrupt-onset erythroderma refractory to cyclosporine and acitretin. The patient complains of fissuring of the palms and soles and of being cold and pruritic but has been able to continue his work as a financial analyst. No new med- ications were initiated before the onset of erythroderma, and 0738-081X/$ see front matter D 2005 Published by Elsevier Inc. doi:10.1016/j.clindermatol.2004.06.018 * Corresponding author. Tel.: +1 860 679 4176; fax: +1 860 679 1267. E-mail address: rothe@nsol.uchc.edu (M.J. Rothe). Clinics in Dermatology (2005) 23, 206217 discontinuation of medications was unhelpful. The patients past medical history is significant for hypertension and alcoholism in recovery. Personal and family history are negative for psoriasis and atopy. Physical examination shows a diffuse salmon-colored erythroderma of the skin with only rare small spared areas, keratoderma, mild ectropion, and scattered excoriations. Multiple biopsies show spongiotic dermatitis; one biopsy shows focal follicular plugging and focal parakeratosis alternating with orthokeratosis, both horizontally and vertically (Fig. 1). A presumptive diagnosis of pityriasis rubra pilaris is made. The patient is referred to a hepatologist for clearance to initiate methotrexate therapy. While awaiting results of the hepatology evaluation, the patient develops new-onset pain in his sacroiliac joints and fingers. He is evaluated by rheumatology and the diagnoses of psoriatic arthritis and probable psoriatic erythroderma are made. There is a gradual response to methotrexate 25 mg weekly with only few small residual psoriatic plaques. The patient is ultimately able to taper off methotrexate with remission of his joint and skin disease. Case 2 In November 1998, a 26-year-old woman with a 5-year history of psoriasis vulgaris is evaluated for worsening disease failing to clear with topical steroids. A 30-treatment trial of broadband ultraviolet B is ineffective. Psoralen-UV- A therapy is initiated with an initial response followed by a flare that eventuates into erythroderma. Multiple biopsies are obtained and only one reveals the definitive changes of psoriasis (Figs. 2 and 3). Over the course of 5 years the erythroderma has waxed and waned but there has been only a partial response to topical therapy, methotrexate, and Table 1 Differential diagnosis Dermatoses Psoriasis Atopic dermatitis CTCL Pityriasis rubra pilaris Superficial pemphigus Bullous pemphigoid Contact dermatitis Chronic actinic dermatitis Pseudolymphoma 1 Hailey-Hailey 2 Infections Dermatophyte 3,4 Norwegian scabies Toxoplasmosis 5 Histoplasmosis 6,7 Leishmaniasis 8 HIV Tuberculosis 9 Systemic Subacute cutaneous lupus 10 Dermatomyositis 11-14 Acute graft-vs-host disease 15 Postoperative transfusion induced 16 Sarcoidosis 17,18 Thyrotoxicosis 19 Common variable hypogammaglobulinemia 20 Severe combined immune defect with Omenns syndrome 21 Leiners disease Maple syrup urine disease 22 Histiocytosis 23 Hypercalcitonemia 24 Hematologic Hodgkins lymphoma 3,25-27 B-cell lymphoma 28 Anaplastic large cell lymphoma 29 Acute myelomonocytic leukemia 30 Adult T-cell leukemia 31 Chronic lymphocytic leukemia 25 Reticulum cell sarcoma 32 Myelodysplasia 33 Chronic eosinophilic leukemia 34 Malignancy Prostate 3,4 Lung 3,4,35 Thyroid 3 Liver 3,36 Breast 4 Ovary 4 Fallopian tube 37 Rectum 4 Esophagus 38 Stomach 35,39 Melanoma 4,40 Buschke-Loewenstein tumor (a verrucous carcinoma on anogenital mucosal surfaces) 41 Fig. 1 Biopsy changes consistent with pityriasis rubra pilaris demonstrating follicular plugging and alternating orthokeratosis and parakeratosis (hematoxylin and eosin, original magnification 20 ). Life-threatening erythroderma: diagnosing and treating the bred manQ 207 cyclosporine alone and in combination with mycophenolate mofetil. The patients care is complicated by obesity, underlying hypertension and diabetes, and noncompliance. She is engaged to be married and interested in conceiving within the next several years. She has required hospitaliza- tion for secondary infection and shows partial improvement of the erythroderma during the admission. The patients internist has been reluctant to approve treatment with a biologic agent because of poor control of the diabetes secondary to noncompliance. Case 3 A 40-year-old man reports the abrupt onset of near erythroderma (Fig. 4) after treatment with clindamycin for a dental abscess while on a golf trip to Florida in February 2003. There is no personal or family history of atopy or psoriasis. Past medical history is significant for hypertension and hyperlipidemia. There is no resolution of the eruption upon discontinuation of his systemic medications, which are subsequently restarted. Examination shows diffuse erythema of the face with lichenified plaques of the forehead and multiple excoriations of the scalp, widespread scaling and erythema of the trunk and the extremities with some areas of sparing, and circinate plaques with peripheral desquamation affecting the thighs and buttocks. Biopsy reveals spongiotic dermatitis and periodic acid-Schiff (PAS) stain is negative. Direct immunofluorescence is negative. There is no improve- ment with topical therapy and antihistamines, but there is partial improvement while the patient is on a business trip to South Carolina in the spring. The patient is reluctant to begin empiric therapy with methotrexate and his internist believes the patient requires ongoing treatment with atorvastatin, which precludes concomitant treatment with cyclosporine. Because of partial improvement with sun exposure, the patient agrees to therapy with narrowband ultraviolet B in June 2003. By October 2003, the lower extremities and buttocks are completely clear, but there are residual small plaques with silvery scale over the trunk and proximal upper extremities and persistence of lichenified plaques over the forehead. The patient declines biopsy of the residual eruption but plans to continue phototherapy until a month- long trip to Florida. Case 4 A 42-year-old black woman with a history of atopic dermatitis presented to her internist with weight loss, fatigue, and erythroderma. Previously she had been healthy and on no medications. Physical examination shows erythroderma, diffuse alopecia of the scalp and loss of the lateral eyebrows, peripheral lymphadenopathy, erosions of the hard palate, punctate purpura affecting the pulps of several fingers, and dilated vessels about the nail folds. Fig. 2 Biopsy demonstrating psoriasis with epidermal hyperpla- sia, hypogranulosis, and spongiform pustular formation (hematox- ylin and eosin, original magnification 2.5 ). Fig. 3 Higher magnification of spongiform pustule within the epidermis (hematoxylin and eosin, original magnification 20 ). Fig. 4 Patient in case 3 with widespread erythema and areas of spared skin. M.J. Rothe et al. 208 Laboratory examination reveals a decreased white blood cell count and antinuclear antibody test is positive at 1:1280 rim pattern. Skin biopsy shows an interface dermatitis (vacuolar alteration and a superficial as well as interface lymphohis- tiocytic infiltrate) (Fig. 5). Her erythroderma clears with oatmeal baths and mid potency topical steroids. She was referred to rheumatology for further workup and manage- ment of her collagen vascular disease. Case 5 A 60-year-old man with a long history of psoriasis vulgaris was referred to the university in November 1993 for management of a flare refractory to topical therapy and etretinate. Physical examination shows a shivering patient with widespread salmon-colored erythema of the face, trunk, and extremities with some clear areas. The margins of plaques adjacent to spared areas show collarettes (Fig. 6). Biopsy of lesional skin shows predominantly eosinophilic spongiosis (Fig. 7) without definitive evidence of acanthol- ytic keratinocytes. Direct immunofluorescence of perile- sional skin is positive for intercellular IgG particularly prominent in the superficial portion of the epidermis. Pemphigus foliaceus clears with pulse steroids, and meth- otrexate provides chronic control of his psoriasis and pemphigus for the following 10 years. Case 6 An 80-year-old woman with Alzheimers disease who resides in a nursing home is referred to the university for progressively worsening atopic dermatitis despite topical and systemic steroid therapy. Physical examination reveals widespread erythema (Fig. 8) sparing only her face and Fig. 7 Histology demonstrated eosinophilic spongiosis (hema- toxylin and eosin, original magnification 10 ). Fig. 8 Elderly patient in case 6 with near erythroderma. Scabies preparation with a burrow shows mites, eggs, and fecal material. Fig. 5 Biopsy demonstrating an interface dermatitis (hematox- ylin and eosin, original magnification 20 ). Fig. 6 Clinically, collarettes are noted indicating a previously ruptured blister. Life-threatening erythroderma: diagnosing and treating the bred manQ 209 some areas over her chest, keratoderma, and fingernail dystrophy. Closer examination of the primary lesions of her chest shows coalescing burrows. Scabies preparation is positive. The patient is successfully treated with several courses of permethrin cream. Epidemiologic and clinical features of erythroderma The above cases are illustrative of the varied clinical presentations of erythroderma. There are multiple published epidemiologic studies of erythrodermic patients. 3,4,25, 26,32,35,42-48 A male predominance has been observed, with a male-to-female ratio ranging from 2:1 to 4:1. The average reported age of affected patients is 41 to 61 years, with most published series excluding children. The most commonly diagnosed etiologies are psoriasis, spongiotic dermatitis, drug Fig. 9 Patient with erythrodermic psoriasis and classic plaques on elbows. Table 2 Drugs implicated in erythroderma Allopurinol 25,44,47,53 Amiodarone 54 Antimalarials 3,25,32,50,55 Arsenicals 54 Aspirin 54 Aztreonam 54 Barbiturates 55 Bromodeoxyuridine 56 Bupropion 57 Captopril 58 Carbamazepine 47,53,59 Carboplatin 60 Cefoxitin 61,62 Chlorpromazine 44 Chlorpropamide 54 Cimetidine 63 Cisplatin 64 Clodronate 65 Clofazimine 66 Codeine 3 Dapsone 67,68 Dideoxyinosine 69 Diltiazem 70 Doxycycline 71 Ephedrine 72 Epoprostenol 73 Etumine 47 Erythropoietin 74 Ethylenediamine 75 Fluindione 76 Fluorouracil 54 Gentamicin 77 Gold 3,32,44,53 Hypericum (St. Johns wort) 78 Indinavir 79 Interleukin-2 80 Iodine 3 Isoniazid 25,26,46 Isosorbide dinitrate 25 Lamotrigine 81 Lithium 82 Mercurials 3,26 Mexiletine 54 Minocycline 54 Neomycin 54 Nifedipine 83 Omeprazole 84 Penicillin 3,25,26,32 Phenobarbital 85 Phenolphthalein 3 Phenothiazines 54 Phenylbutazone 46 Phenytoin 25,35,51,86,87 Practolol 44 Propolis 88 Pseudoephedrine 89 Quinidine 32,53 Ranitidine 54 Retinoids 90 Rhus (lacquer) 91 Ribostamycin 92 Streptomycin 3,46 Sulfasalazine 52 Sulfonamide antibiotics 3,25 Sulfonylureas 54 Terbinafine 93 Terbutaline 25 Tetrachloroethylene 3 Thalidomide 94,95 Thiacetazone 46 Thiazide 25 Timolol eyedrops 96 Trimethoprim 44 Tumor necrosis factor-a 80 Vancomycin 97 Zidovudine 98 Table 2 (continued) M.J. Rothe et al. 210 reactions, and cutaneous T-cell lymphoma (CTCL). Eryth- roderma is classified as idiopathic in 9% to 47% of cases. Erythroderma may be attributable to an exacerbation of a preexisting dermatosis in more than half of patients. 49 Usually, patients with erythroderma secondary to psoriasis or spongiotic dermatitis have a history of more localized disease before the onset of erythroderma. 43 In a review of 50 patients with psoriatic erythroderma, Boyd and Menter 50 observed an average age of onset of 48 years, a male-to- female ratio of 2:1, and an average of 14 years between the onset of psoriasis and the development of erythroderma. Triggers of psoriatic erythroderma include withdrawal of topical or systemic corticosteroids; abrupt discontinuation of methotrexate; topical irritants such as tars; systemic medications such as antimalarials, lithium, and terbinafine; phototherapy burns; infection, including HIV; pregnancy; emotional stress; and systemic illness. Classic plaques of psoriasis vulgaris may be evident in early and remitting stages of erythroderma (Fig. 9). Psoriatic arthritis and psoriatic nail changes may be present in some cases. It is important to consider other possible etiologies even in patients who may have a clear history of psoriasis or atopic dermatitis or who may have features of psoriasis vulgaris on examination. Eugster et al 49 describe 7 patients with malignancy-related erythroderma, 5 of whom had a history of preexisting dermatosis. Onset of erythroderma due to drug reactions is typically sudden and rapid and its resolution is typically faster than cases of erythroderma due to other causes. A notable exception occurs when erythroderma accompanies systemic drug hypersensitivity reactions due to antibiotics, anticon- vulsants, and allopurinol. Hypersensitivity develops within 2 to 5 weeks after the medication is started and may persist for weeks despite discontinuation of the medication. Fever, leukocytosis with eosinophilia, edema, lymphadenopathy, organomegaly, and liver and renal dysfunction are charac- teristic. 51,52 Table 2 provides a comprehensive list of drugs implicated in drug-induced erythroderma. Sezary syndrome is by definition manifested as eryth- roderma, lymphadenopathy, hepatosplenomegaly, and cir- culating Sezary cells. Pruritus is typically severe. Long- standing disease is characterized by painful fissured keratoderma (Fig. 10) and leonine facies secondary to lymphomatous infiltration of the skin (Fig. 11). 99 Pityriasis rubra pilaris often begins as a seborrheic dermatitis-like eruption of the scalp that quickly evolves, especially after intense sun exposure, into a generalized salmon-colored erythema with islands of sparing. Kerato- derma is a prominent and early feature. Follicular pink papules affecting the dorsal fingers, wrists, and elbows may be present. The diagnosis of erythroderma secondary to immuno- bullous disease is most readily made when blisters and erosions are present. Superficial pemphigus may show impetigo-like erosions or collarettes indicative of a ruptured blister. Tense blisters are usually, but not always, a feature of erythrodermic bullous pemphigoid. 100 Pathognomonic features may facilitate the diagnosis of erythrodermic dermatomyositis (eg, Gottrons papules, heliotrope, poikiloderma, periungual telangiectasis, muscle weakness), 12,13 chronic actinic dermatitis (eg, photoaccen- tuation), erythrodermic sarcoidosis (eg, apple jelly lesions), 17 and Norwegian scabies (eg, burrows). Symptoms common to erythroderma of any etiology are thermoregulatory disturbance, malaise, fatigue, and pruritus. Lichenification, diffuse alopecia, dermatopathic lymphade- nopathy, keratoderma, nail dystrophy, and ectropion are signs common to long-standing erythrodermas of any Fig. 10 Patient with fissuring of Sezary. Fig. 11 Histology demonstrating epidermotropism of enlarged mononuclear cells with minimal spongiosis consistent with CTCL (hematoxylin and eosin, original magnification 25 ). Life-threatening erythroderma: diagnosing and treating the bred manQ 211 etiology 47 (Fig. 12). Pitting pretibial and pedal edema is observed in 50% of erythrodermic patients. 73,94 Laboratory investigations Laboratory findings are most often not diagnostic for etiology of erythroderma. Common abnormalities found in erythrodermic patients include leukocytosis, anemia, elevat- ed erythrocyte sedimentation rate, lymphocytosis, eosino- philia, and increased serum IgE. 3,25,32,43,44,46,47,53,101 In a clinical study by Sigurdsson et al, 53 13 of 102 patients had an erythrocyte sedimentation rate higher than 30 mm/h, 8 of whom had idiopathic erythroderma. Other findings include elevated creatinine level, elevated uric acid level, and lowered serum protein levels. 26,47 Eosinophilia is not diagnostic for etiology. Eosinophil count greater than 1.0 10 9 /L, however, was found in 20% of patients. 53 The negative nitrogen balance found in chronic erythroderma can lead to findings of hypoalbuminemia. 32 Sezary cell count analysis can be used for diagnosis of Sezary syndrome. More than 20% circulating Sezary cells is diagnostic for Sezary syndrome, whereas less than 10% is nonspecific. 45,53 Sezary cells are found in these lower numbers in many benign dermatoses, including atopic dermatitis, psoriasis, lichen planus, discoid lupus, and parapsoriasis. 102 Immunophenotyping of skin lymphocytes can be used to differentiate Sezary syndrome from actinic reticuloid. Sigurdsson et al 53 found predominance of CD8 + lympho- cytes in 7 of 12 patients with actinic reticuloid. Differen- tiation between Sezary syndrome and actinic reticuloid can also be accomplished via nuclear contour index of peripheral blood lymphocytes. 103 Clinical data combined with multiple skin biopsies over time are necessary. T-cell receptor b gene rearrangement on peripheral blood smears is used for sensitive and specific differentiation of Sezary syndrome from other benign forms of erythroderma. 104 This technique has been applied to skin biopsies as well; in recent studies, specificity has been 100% Fig. 12 Diffuse alopecia in patient with chronic idiopathic erythroderma. Table 3 Histologic differential diagnosis of the erythrodermic patient Disease Diagnostic histological clue Actinic reticuloid Atypical mononuclear cells admixed in a superficial, lichenoid, and deep dermal infiltrate; overlying lichen simplex chronicus with or without spongiosis Atopic dermatitis Superficial perivascular dermal infiltrate containing eosinophils with overlying spongiosis; can be seen with eosinophilic spongiosis; with or without lichen simplex chronicus Contact dermatitis Same as atopic dermatitis CTCL/Sezary Mononuclear cells within the epidermis (exocytosis) unassociated with significant spongiosis (Fig. 7) Dermatomyositis/Subacute cutaneous lupus erythematosus Interface dermatitis with vacuolar alteration, often thickening of the basement membrane, colloid bodies, increased dermal mucin Dermatophytosis Hyphae within stratum corneum, mounds of parakeratosis Drug eruption Interface dermatitis with necrotic keratinocytes Acute graft-vs-host disease Vacuolar alteration often with bsatellite cell necrosisQ of keratinocytes (Fig. 8) Ichthyoses Changes of the specific type of inherited ichthyosis (epidermolytic hyperkeratosis) or nondiagnostic changes Idiopathic Nonspecific changes (usually subacute or chronic spongiotic dermatitis-like changes) Lymphoproliferative diseases Superficial, deep, and interstitial dermal infiltrate of atypical mononuclear cells Paraneoplastic Nonspecific changes Pemphigoid Subepidermal bulla with dermal eosinophils and/or eosinophilic spongiosis (Fig. 9) Pemphigus Intraepidermal bulla with acantholysis and/or eosinophilic or neutrophilic spongiosis Paraneoplastic pemphigus Suprabasal acantholysis, dyskeratotic keratinocytes, vacuolar alteration with lichenoid inflammation Pityriasis rubra pilaris Epidermal hyperplasia with horizontal and vertical alternating orthokeratosis and parakeratosis; dilated plugged follicular infundibulum Psoriasis Psoriasiform epidermal hyperplasia with mounds or confluent parakeratosis layered with neutrophils, hypogranulosis, and dilated tortuous papillary blood vessels (Fig. 10) Sarcoidosis Epithelioid dermal granulomas with little or no mantle of surrounding lymphocytes Scabies Superficial and deep perivascular and interstitial inflammation with many eosinophils; frequent spongiosis; stratum corneum with mite, excreta, crusting possible Seborrheic dermatitis Spongiotic psoriasiform dermatitis with parakeratosis often with neutrophils at the lips of the follicular ostia Stasis with autoeczematization Spongiotic dermatitis often with some eosinophils M.J. Rothe et al. 212 when used in conjunction with clinical and histological features. 105,106 Histopathology The histopathology of erythroderma varies depending on the underlying etiology (Table 3). Therefore, careful examination of the epidermis and dermis from a punch biopsy is recommended. In approximately one third of erythrodermic patients, however, the biopsies fail to reveal the diagnostic features of any specific disease. In addition, only 50% of any specific biopsy submitted on these patients are likely to reveal the underlying cause. 107,108 This is in part because the specific features of the disease can be masked by nonspecific features associated with the eryth- roderma. Therefore, multiple simultaneous punch skin biopsies are recommended to enhance the possibility that one might show the distinctive changes of the underlying disease process that has resulted in the patients erythro- derma. In addition to routine histology, special stains, immunoperoxidase studies, gene rearrangement studies, and direct immunofluorescence have proven to be very helpful. Algorithm of approach to the erythrodermic patient Erythrodermic patient presents to your office. q Obtain history of possible precipitating causes and pertinent past medical history and family history. Check medication history. q Full skin examination of patient for any telltale sign of underlying skin diseases. Check nails and mucosa. Check lymph nodes and rule out organomegaly. Take vital signs to establish patient stability. q Perform multiple skin biopsies for routine histology. Simultaneously initiate cool down topical therapies and supportive care immediately. q If appropriate, biopsy enlarged lymph nodes. If appropriate, evaluate complete blood cell count, CD4:CD8 ratio, and antinuclear antibodies. If appropriate order chest x-ray. Consider patch testing if appropriate. If appropriate, rebiospy for direct immunofluoresence to rule out immunobullous disease and/or rebiopsy for gene rearrangement studies to rule out lymphoproliferative disease. If no underlying etiology identified, refer to primary care physician to rule out underlying systemic disease. q Onceunderlyingetiologyisestablished, treat appropriately. Systemic complications Systemic complications of erythroderma include infec- tion, fluid and electrolyte imbalances, thermoregulatory disturbance, high output cardiac failure, 109 acute respiratory distress syndrome, 110 and gynecomastia. The inflamed, fissured, and excoriated skin is susceptible to bacterial colonization, and sepsis occurs occasionally. Staphylococcal sepsis is especially a risk for patients with CTCL and HIV- positive erythroderma. 110-112 Fluid and electrolyte imbal- ances occur from loss of fluid, electrolytes, and protein from leaky capillaries. Increased perfusion of the skin is associated with high output cardiac failure and temperature dysregulation. High output cardiac failure is associated with the shunting of blood through the inflamed skin, and is of particular concern in elderly patients or patients with preexisting cardiac conditions. 109 These leaky dilated capillaries also allow evaporation of heat, which contributes to thermoregulatory disturbance, in addition to inability to respond to changes in temperature via vasoconstriction and vasodilation. 113 There is also an increase in the basal metabolic rate, which elevates the skin temperature. 50 Erythroderma increases protein loss by 25% to 30% in psoriatic erythroderma, and 10% to 15% from nonpsoriatic erythroderma. 114 This protein loss causes a negative nitrogen balance that can be manifest by edema, muscle wasting, and hypoalbuminemia. Increased circulating levels of adhesion molecules intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin have been found in patients with erythroderma secondary to psoriasis, eczema, and patients with CTCL. The adhesion molecule expression on endo- thelial cells was examined in patients with erythroderma, and there were no differences found in adhesion molecule, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, P-selectin, and E-selectin expression in differ- ent types of erythroderma. Sezary syndrome was found to have higher mean expression of all adhesion molecules than patients with other forms of CTCL, but it was not statistically significant. Sigurdsson et al 115 suggest that the similarities in adhesion molecule expression in various types of erythroderma may correlate with the similarities in the clinical examination of patients with erythroderma of diverse etiologies. Cytokine profiles in dermal infiltrates show differences between types of erythroderma, with benign erythroderma showing a T-helper 1 cytokine profile, whereas Sezary syndrome shows a T-helper 2 cytokine profile. This may indicate that there are different pathophy- siogical mechanisms for development of erythroderma. 116 Treatment The initial approach to the management of erythroderma of any etiology includes attention to nutrition and fluid and Life-threatening erythroderma: diagnosing and treating the bred manQ 213 electrolyte replacement and the institution of gentle local skin care measures. Oatmeal baths and wet dressings to weeping or crusted sites should be followed by application of bland emollients and low-potency topical corticosteroids. Higher potency topical corticosteroids are not recommended because of risk for systemic absorption secondary to the extensive body surface area and the enhanced cutaneous permeability. 117 Similarly, increased absorption of topical tacrolimus has been observed in a patient with leukemic erythroderma, posing the risk for nephrotoxicity and warranting monitoring of tacrolimus blood levels. 118 Topical immunomodulators may also be irritating and poorly tolerated by the erythrodermic patient. Other skin irritants such as tars and hydroxy acid moisturizers are also avoided. A warm and humidified environment will increase patient comfort, prevent hypothermia, and improve mois- turizing of the skin. Sedating oral antihistamines are prescribed to relieve pruritus and anxiety. Systemic antibiotics are required for patients with secondary infec- tion. In cases in which a drug-induced erythroderma has not been excluded, consideration should be given to discontin- uation of all nonessential medications. Diuretics may be necessary when peripheral edema fails to respond to leg elevation and local skin care. Patients with evidence of cardiovascular or respiratory failure require hospitalization for urgent care. Systemic dermatologic therapy may be required to maintain improvement achieved with local measures or to control erythroderma refractory to local measures. Systemic corticosteroids are recommended for patients with systemic drug hypersensitivity reactions and should obviously be avoided in patients with possible underlying psoriasis. Bio- logics are an important therapeutic advance in the treatment of labile psoriasis; published reports describe rapid and dramatic control of erythrodermic and generalized pustular psoriasis with infliximab. Infusions of 5 to 10 mg/kg infliximab have been found to substantially completely clear erythrodermic psoriasis in 3 to 4 weeks and may be an effective alternative to conventional treatments for acutely ill patients. 119,120 When the specific cause of erythroderma remains undiagnosed, empiric therapy can be considered with agents such as systemic corticosteroids, methotrexate, cyclosporine, mycophenolate mofetil, and acitretin. A strong but not confirmed suspicion for the diagnosis of psoriasis should preclude the use of systemic corticosteroids. Similarly, immunosuppressive agents such as cyclosporine should be avoided unless a diagnosis of CTCL has been excluded by the most sophisticated and up-to-date laboratory testing available. Natural course of disease The prognosis of erythroderma is dependent on the underlying etiology. With the exception of severe systemic hypersensitivity reactions, drug-induced erythroderma clears readily with discontinuation of the causative drug. 44,121 Erythroderma secondary to psoriasis and spongi- otic dermatitis usually improves within several weeks to several months, although cases of chronic psoriatic atopic erythroderma are not uncommon. Erythrodermic psoriasis may recur in 15% of patients after initial clearing. 50 Erythroderma secondary to CTCL or other malignancy is often persistent and refractory. One third of patients with idiopathic erythroderma have been observed to show complete remission, 4,45 whereas 50% of patients demon- strate partial remission. 45 Those with chronic idiopathic erythroderma are at high risk to evolve to CTCL. 25,45,47 Early published series of erythroderma reported a significant mortality rate from complications including pneumonia, cardiac failure, and sepsis. 3,32,42 Deaths were most common in patients with pemphigus foliaceus, lymphoproliferative malignancy, severe drug reactions, and idiopathic erythroderma. 32 More recent series have found a decreased mortality rate with most deaths occurring in patients with malignancy-related erythroderma. 25,44,53 Deaths have also been reported in patients with high output cardiac failure. 47 Conclusions The erythrodermic patient requires immediate attention. Unfortunately, physical examination, routine laboratory findings, and even initial biopsies may be nondiagnostic, often making these patients challenging to diagnose and treat. Multiple biopsies and, often, repeat biopsies may be necessary to make a definitive diagnosis. Although death from cardiac failure, sepsis, capillary leakage syndrome, and even respiratory distress syndrome have been reported, early medical intervention and newer dermatologic therapies have improved the prognosis of this devastating dermatologic condition. References 1. Ban M, Ichihashi N, Kitajima Y. Cutaneous plasmacytic pseudolym- phoma with erythroderma. Int J Dermatol 1998;37:778- 80. 2. Marsch WCh, Stuttgen G. Generalized Hailey-Hailey disease. Br J Dermatol 1978;99:553- 60. 3. Nicolis GD, Helwig EB. Exfoliative dermatitis: a clinicopathologic study of 135 cases. Arch Dermatol 1973;108:788- 97. 4. Thestrup-Pedersen K, Halkier-Sorensen L, Sogaard H, et al. The red man syndrome: exfoliative dermatitis of unknown etiology: a description and follow-up study of 38 patients. J Am Acad Dermatol 1988;18:1307- 12. 5. Fernandez DF, Wolff AH, Bagley MP. Acute cutaneous toxoplasmosis presenting as erythroderma. Int J Dermatol 1994;33:129- 30. 6. Samovitz M, Dillon TK. Disseminated histoplasmosis presenting as exfoliative erythroderma. Arch Dermatol 1970;101:216- 9. 7. Yungmann MP, Ford MJ. Histoplasmosis presenting as erythroderma in a patient with the acquired immunodeficiency syndrome. Int J Dermatol 2003;42:636- 9. M.J. Rothe et al. 214 8. Belda-Mira A, Pascual-Izuel JM, Prats-Manez A, et al. Erythroderma as presentation form of visceral leishmaniasis in a patient with human immunodeficiency virus infection. Rev Clin Exp 1992; 191:454. 9. Chan YC, Yosipovitch G. Erythroderma: an unusual presentation of pulmonary tuberculosis. Br J Dermatol 2003;148:346- 8. 10. DeSpain J, Clark DP. Subacute cutaneous lupus erythematosus presenting as erythroderma. J Am Acad Dermatol 1988;19:388- 92. 11. Miyagawa S, Okazaki A, Minowa R, et al. Dermatomyositis presenting as erythroderma. J Am Acad Dermatol 1992;26:489- 90. 12. Nousari HC, Kimyai-Asadi A, Spegman DJ. Paraneoplastic derma- tomyositis presenting as erythroderma. J Am Acad Dermatol 1998;39: 653- 4. 13. Pierson JC, Taylor JS. Erythrodermic dermatomyositis. J Am Acad Dermatol 1993;28:136. 14. Ramirez G, Asgerson RA, Khamashta MA, et al. Adult-onset polymyositis-dermatomyositis: description of 25 patients with emphasis on treatment. Semin Arthritis Rheum 1990;20:114- 20. 15. Horn TD, Altomonte V, Volgesang G, et al. Erythroderma after autologous bone marrow transplantation modified by administration of cyclosporine and interferon gamma for breast cancer. J Am Acad Dermatol 1996;34:413- 7. 16. Hisatomi K, Isomura T, Hirano A, et al. Postoperative erythroderma after cardiac operations: the possible role of depressed cell-mediated immunity. J Thorac Cardiovasc Surg 1992;104:648- 53. 17. Feind-Koopmans AG, Lucker GPH, van de Kerkhof PCM, et al. Acquired ichthyosiform erythroderma and sarcoidosis. J Am Acad Dermatol 1996;35:826- 8. 18. Morrison JGL. Sarcoidosis in a child, presenting as an erythroderma with keratotoic spines and palmar pits. Br J Dermatol 1976;95:93- 7. 19. Zemtsov A, Elks M, Shehata B. Throtoxicosis presenting as generalized pruritic exfoliative dermatitis and fever. Dermatology 1992;184:157. 20. White WB, Shornick JK, Grant-Kels JM, et al. Erythroderma with spongiotic dermatitis: association with common variable hypogam- maglobinemia. Am J Med 1985;78:523- 8. 21. Pupo RA, Tyring SK, Raimer SS, et al. Omenns syndrome and related combined immunodeficiency syndromes: diagnostic conside- rations in infants presenting with persistent erythroderma and failure to thrive. J Am Acad Dermatol 1991;25:442- 6. 22. Northrup H, Sigman ES, Hebert AA. Exfoliative erythroderma resulting from inadequate intake of branched-chain amino acids in infants with maple syrup urine disease. Arch Dermatol 1993;129: 384- 5. 23. Patrizi A, Pileri S, Rivano MT, et al. Malignant histiocytosis presenting as erythroderma. Int J Dermatol 1990;29:214- 6. 24. Schrivener Y, Jeandidier N, Asch PH, et al. Erythrodermia induced by hypercalcitoninemia. Ann Dermatol Venereol 2002;129:221- 4. 25. King Jr LE, Dufresne Jr RG, Lovett GL, et al. Erythroderma: review of 82 cases. South Med J 1986;79:1210- 5. 26. Pal S, Haroon TS. Erythroderma: a clinico-etiologic study of 90 cases. Int J Dermatol 1998;37:104- 7. 27. Arita K, Akiyama M, Sakai T, et al. Severely hyperkeratotic erythroderma associated with Hodgkins disease: does a high serum level of granulocyte-colony stimulating factor contribute to formation of skin lesions? J Am Acad Dermatol 2003;49:772- 3. 28. Leong AS, Cowled PA, Zalewski PD, et al. Erythroderma, an unusual manifestation of B cell lymphoma. Br J Dermatol 1978;99: 99- 106. 29. Denton K, Wilson CL, Venning VA. Primary cutaneous anaplastic large-cell lymphoma with a prolonged erythrodermic prodrome. Br J Dermatol 1992;126:297- 300. 30. De Connick A, De Hou MF, Peters O, et al. Aleukemic leukemia cutis: an unusual presentation of adult myelomonocytic leukemia. Dermatologica 1986;172:272- 5. 31. Hashizume H, Nakayama F, Oku T, et al. Adult T-cell leukemia with regression of erythroderma and simultaneous emergence of leukemia. J Am Acad Dermatol 1992;27:846- 9. 32. Abrahams I, McCarthy JT, Sanders SL. 101 cases exfoliative dermatitis. Arch Dermatol 1963;87:96- 101. 33. Chu P, Aitchison R, Jones PA. Myelodysplasia presenting as erythroderma. Postgrad Med J 1987;63:481- 2. 34. Granjo E, Lima M, Lopes JM, et al. Chronic eosinophilic leukaemia presenting with erythroderma, mild eosinophilia and hyper-IgE: clinical, immunological and cytogenetic features and therapeutic approach. Acta Haematol 2002;107:108- 12. 35. Sigurdsson V, Toonstra J, Hezemans-Boer M, et al. Erythroderma: a clinical and follow-up study of 102 patients, with special emphasis on survival. J Am Acad Dermatol 1996;35:53- 7. 36. Nishijima S. Papuloerythroderma associated with hepatocellular carcinoma. Br J Dermatol 1998;139:1115- 6. 37. Axelrod JH, Herbold DR, Freel JH, et al. Exfoliative dermatitis: presenting sign of fallopian tube carcinoma. Obstet Gynecol 1988;71:1045. 38. Deffer TA, Overton-Keary PP, Goette DK. Erythroderma secondary to esophageal carcinoma. J Am Acad Dermatol 1985;13:311- 3. 39. Harper TG, Latuska RF, Sperling HV. An unusual association between erythroderma and an occult gastric carcinoma. Am J Gastroenterol 1984;79:921- 3. 40. Thami G, Sharma NL, Sharma A, et al. Exfoliative dermatitis and malignant melanoma: coincidence or association? Int J Dermatol 1996;35:682. 41. Antony FC, Ardern-Jones M, Evans AV, et al. Giant condyloma of Buschke-Loewenstein in association with erythroderma. Clin Exp Dermatol 2003;28:46- 9. 42. Wilson HTH. Exfoliative dermatitis: its etiology and prognosis. Arch Dermatol 1954;69:577- 88. 43. Gentele H, Lodin A, Skog E. Dermatitis exfoliativa: cases admitted in the decade 1948-1957 to the dermatological clinic, Karolinska Sjukhuset, Stockholm, Sweden. Acta Derm Venereol 1958;38:296- 302. 44. Hasan T, Jansen CT. Erythroderma: a follow-up of fifty cases. J Am Acad Dermatol 1983;8:836- 40. 45. Sigurdsson V, Toonstra J, van Vloten WA. Idiopathic erythroderma: a follow-up study of 28 patients. Dermatology 1997;194:98- 101. 46. Sehgal VN, Srivastava G. Exfoliative dermatitis: a prospective study of 80 patients. Dermatologica 1986;173:278- 84. 47. Botella-Estrada R, Sanmartin O, Oliver V, et al. Erythroderma: a clinicopathological study of 56 cases. Arch Dermatol 1994;130: 1503- 7. 48. Tomasini C, Aloi F, Solaroli C, et al. Psoriatic erythroderma: a histopathologic study of forty-five patients. Dermatology 1997;194: 102- 6. 49. Eugster R, Kissling S, Brand CU. Clinical aspects and etiology of erythroderma: an analysis of 64 cases. Schweiz Rundsch Med Prax 2001;90:1449- 54. 50. Boyd AS, Menter A. Erythrodermic psoriasis: precipitating factors, course, and prognosis in 50 patients. J Am Acad Dermatol 1989;21: 985- 91. 51. Chopra S, Levell NJ, Cowley G, et al. Systemic corticosteroids in the phenytoin hypersensitivity syndrome. Br J Dermatol 1996;134: 1109- 12. 52. Tohyama M, Yahata Y, Yasukawa M, et al. Severe hypersensitivity syndrome due to sulfasalazine associated with reactivation with human herpesvirus 6. Arch Dermatol 1998;134:1113- 7. 53. Sigurdsson V, Toonstra J, Hezemans-Boer M, et al. Erythroderma: a clinical and follow-up study of 102 patients, with special emphasis on survival. J Am Acad Dermatol 1996;35:53- 7. 54. Freedberg IM. Exfoliative dermatitis. In: Freedberg IM, Eisen AZ, Wolff K, et al, editors. Fitzpatricks dermatology in general medicine, 5th ed. Philadelphia7 WB Saunders; 1999. p. 534. Life-threatening erythroderma: diagnosing and treating the bred manQ 215 55. Slagel GA, James WD. Plaquenil-induced erythroderma. J Am Acad Dermatol 1985;12:857- 62. 56. Fine J-D, Breathnach SM. Distinctive eruption characterized by linear supravenous papules and erythroderma following broxuridine (bro- modeoxyuridine) therapy and radiotherapy. Arch Dermatol 1986;122: 199- 200. 57. Cox NH, Gordon PM, Dodd H. Generalized pustular and erythroder- mic psoriasis associated with bupropion treatment. Br J Dermatol 2002;146:1061- 3. 58. Solinger AM. Exfoliative dermatitis from captopril. Cutis 1982;29: 473- 4. 59. Troost RJJ, Oranje AP, Lijnen RLP, et al. Exfoliative dermatitis due to immunologically confirmed carbamazepine hypersensitivity. Pediatr Dermatol 1996;13:316- 20. 60. Polyzos A, Tsavaris N, Kosmas C, et al. Hypersensitivity reactions to carboplatin administration are common but not always severe: a 10- year experience. Oncology 2001;61:129- 33. 61. Kannangara DW, Smith B, Cohen K. Exfoliative dermatitis during cefoxitin therapy. Arch Intern Med 1982;142:1031- 2. 62. Tietze KJ, Gaska JA. Cefoxitin-associated exfoliative dermatitis. Clin Pharm 1983;2:582- 4. 63. Yantis PL, Bridges ME, Pittman FE. Cimetidine-induced exfoliative dermatitis. Dig Dis Sci 1980;25:73- 4. 64. Lee TC, Hook CC, Long HJ. Severe exfoliative dermatitis associated with hand ischemia during cisplatin therapy. Mayo Clin Proc 1994;69:80- 2. 65. Pajus I, Lestang P, Liote F, et al. Erythroderma after clodronate treatment. BMJ 1993;307:484. 66. Pavithran K. Exfoliative dermatitis after clofazimine. Int J Lepr Other Mycobact Dis 1985;53:645- 6. 67. Patki AH, Menta JM. Dapsone-induced erythroderma with Beaus lines. Lepr Rev 1989;60:274- 7. 68. Rao PN, Lakshmi TS. Increase in the incidence of dapsone hypersensitivity syndromean appraisal. Lepr Rev 2001;72:57- 62. 69. Just M, Carrascosa JM, Ribera M, et al. Dideoxyinosine-associated Ofuji papuloerythroderma in an HIV-infected patient. Dermatology 1997;195:410- 1. 70. Wittal RA, Fischer GO, Georgouras KE, et al. Skin reactions to diltiazem. Australas J Dermatol 1992;33:11- 8. 71. Batinac T, Zamolo G, Jonjic N, et al. Angioimmunoblastic lymphadenopathy with dysproteinemia following doxycycline ad- ministration. Tumori 2003;89:91- 5. 72. Catlin DH, Sekera M, Adelman DC. Erythroderma associated with ingestion of an herbal product. West J Med 1993;159:491- 3. 73. Ahearn GS, Selim MA, Tapson VF. Severe erythroderma as a complication of continuous epoprostenol therapy. Chest 2002;122: 378- 80. 74. Cuxart M, Just M, Sans R, et al. Generalized exfoliative dermatitis caused by erythropoietin. Med Clin (Barc) 2000;115:158. 75. Bernstein JE, Lorincz AL. Ethylenediamine-induced exfoliative erythroderma. Arch Dermatol 1979;115:360- 1. 76. Sparsa A, Bedane C, Benazahary H, et al. Drug-induced hypersen- sitivity syndrome due to fluindione. Ann Dermatol Venereol 2001;128:1014- 8. 77. Guin JD, Phillips D. Erythroderma from systemic contact dermatitis: a complication of systemic gentamicin in a patient with contact allergy to neomycin. Cutis 1989;43:564- 7. 78. Holme SA, Roberts DL. Erythroderma associated with St. Johns wort. Br J Dermatol 2000;143:1127- 8. 79. Rietsema WJ. Fever, erythroderma, abdominal pain, and renal failure following initiation of indinavir therapy. Clin Infect Dis 1997;25:1268- 9. 80. Asnis LA, Gaspari AA. Cutaneous reactions to recombinant cytokine therapy. J Am Acad Dermatol 1995;33:393- 410. 81. Hurley SC. Lamotrigine update and its use in mood disorders. Ann Pharmacother 2002;36:860- 72. 82. Kuhnley EJ, Granoff AL. Exfoliative dermatitis during lithium treatment. Am J Psychiatry 1979;136:1340- 1. 83. Reynolds NJ, Jones SK, Crossley J, et al. Exfoliative dermatitis due to nifedipine. Br J Dermatol 1989;121:401- 4. 84. Rebuck JA, Rybak MJ, Ramos DP, et al. Omeprazole-induced exfoliative dermatitis. Pharmacotherapy 1998;18:877- 9. 85. Sakai C, Takagi T, Oguro M, et al. Erythroderma and marked atypical lymphocytosis mimicking cutaneous T-cell lymphoma probably caused by phenobarbital. Intern Med 1993;32:182- 4. 86. DIncan M, Souteyrand P, Bignon YJ, et al. Hydantoin-induced cutaneous pseudolymphoma with clinical, pathologic, and immunologic aspects of Sezary syndrome. Arch Dermatol 1992;128: 1371- 4. 87. Kleier RS, Breneman DL, Boiko S. Generalized pustulation as a manifestation of the anticonvulsant hypersensitivity syndrome. Arch Dermatol 1991;127:1361- 4. 88. Horiuchi Y. Propolis-induced erythroderma. J Dermatol 2001;28: 580- 1. 89. Gonzalo-Garijo MA, Perez-Calderon R, de Argila D, et al. Erythroderma to pseudoephedrine in a patient with contact allergy to phenylephrine. Allergol Immunopathol (Madr) 2002;30:239- 42. 90. Wantzin GL, Thomsen K. A new cutaneous side effect of isotretinoin. J Am Acad Dermatol 1985;13:665. 91. Park SD, Lee SW, Chun JH, et al. Clinical features of 31 patients with systemic contact dermatitis due to the ingestions of Rhus (lacquer). Br J Dermatol 2000;142:937- 42. 92. Puig LL, Abadia M, Alomar A. Erythroderma due to ribostamycin. Contact Dermatitis 1989;21:79- 82. 93. Gupta AK, Lynde CW, Lauzon GJ, et al. Cutaneous adverse effects associated with terbinafine therapy: 10 case reports and a review of the literature. Br J Dermatol 1998;138:529- 32. 94. Bielsa I, Teixido J, Ribera M, et al. Erythroderma due to thalidomide: report of two cases. Dermatology 1994;189:179- 81. 95. Hall VC, El-Azhary RA, Bouwhuis S, et al. Dermatologic side effects of thalidomide in patients with multiple myeloma. J Am Acad Dermatol 2003;48:548- 52. 96. Shelley WB, Shelley ED. Chronic erythroderma induce by b- blocker (timolol maleate) eyedrops. J Am Acad Dermatol 1997;37:799- 800. 97. Forrance EA, Goldman MP. Vancomycin-associated exfoliative dermatitis. DICP 1990;24:369- 71. 98. Duque S, de la Puente J, Rodriguez F, et al. Zidovudine-related erythroderma and successful desensitization: a case report. J Allergy Clin Immunol 1996;98:234- 5. 99. Wieselthier JS, Koh HK. Sezary syndrome: diagnosis, prognosis, and critical review of treatment options. J Am Acad Dermatol 1990;22:381- 401. 100. Alonso-Llamazares J, Dietrich SM, Gibson LE. Bullous pemphigoid presenting as exfoliative erythroderma. J Am Acad Dermatol 1998;39:827- 30. 101. Agarwal S, Khuller R, Kalla G, et al. Nose sign of exfoliative dermatitis: a possible mechanism. Arch Dermatol 1992;128:704. 102. Duncan SC, Winkelmann RK. Circulating Sezary cells in hospitalized dermatology patients. Br J Dermatol 1978;99:171- 8. 103. Preesman AH, Schrooyen SJ, Toonstra J, et al. The diagnostic value of morphometry on blood lymphocytes in erythrodermic actinic reticuloid. Arch Dermatol 1995;131:1298- 303. 104. Bakels V, van Oostveen JW, Gordijn RLJ, et al. Diagnostic value of T- cell receptor beta gene rearrangement analysis on peripheral blood lymphocytes of patients with erythroderma. J Invest Dermatol 1991;97:782- 6. 105. Cherny S, Mraz S, Su L, et al. Heteroduplex analysis of T-cell receptor gamma gene rearrangement as an adjust diagnostic tool in skin biopsies for erythroderma. J Cutan Pathol 2001;28: 351- 5. 106. Cordel N, Lenormand B, Courville P, et al. Rearrangement des genes du recepteur des lymphocytes T cutanes par la technique de PCR- M.J. Rothe et al. 216 DGGE pour le diagnostic etiologique des erythrodermies. Ann Dermatol Venereol 2001;128:220- 3. 107. Walsh NMG, Prokopetz R, Tron VA, et al. Histopathology in erythroderma: review of a series of cases by multiple observers. J Cutan Pathol 1994;21:419- 23. 108. Zip C, Murray S, Walsh NMG. The specificity of histopathology in erythroderma. J Cutan Pathol 1993;20:393- 8. 109. Shuster S. High-output cardiac failure from skin disease. Lancet 1963;1:1338- 40. 110. Green MS, Prystowskey JH, Cohen SR, et al. Infectious complications of erythrodermic psoriasis. J Am Acad Dermatol 1996;34:911- 4. 111. Jackow CM, Cather JC, Hearne V, et al. Association of erythrodermic cutaneous T-cell lymphoma, superantigen-positive Staphylococcus aureus, and oligoclonal T-cell receptor Vb gene expression. Blood 1997;89:32- 40. 112. Jaffe D, May LP, Sanchez M, et al. Staphylococcal sepsis in HIV antibody seropositive psoriasis patients. J Am Acad Dermatol 1991;24:970- 2. 113. Marks JM. Erythroderma. Semin Dermatol 1986;5:27- 32. 114. Kanthraj GR, Srinivas CR, Devi PU, et al. Quantitative estimation and recommendations for supplementation of protein lost through scaling in exfoliative dermatitis. Int J Dermatol 1999;38:91- 5. 115. Sigurdsson V, de Vries JM, Toonstra J, et al. Expression of VCAM-1, ICAM-1, E-selectin and P-selectin on endothelium in situ in patients with erythroderma, mycosis fungoides and atopic dermatitis. J Cutan Pathol 2000;27:436- 40. 116. Sigurdsson V, Toonstra J, Bihari IC, et al. Interleukin 4 and interferon- c expression of the dermal infiltrate in patients with erythroderma and mycosis fungoides. An immuno-histochemical study. J Cutan Pathol 2000;27:429- 35. 117. Aalto-Korte K, Turpeinen M. Quantifying systemic absorption of topical hydrocortisone in erythroderma. Br J Dermatol 1995;133: 403- 8. 118. Teshima D, Ikesue H, Itoh Y, et al. Increased topical tacrolimus absorption in generalized leukemic erythroderma. Ann Pharmacother 2003;37:1444- 7. 119. OQuinn RP, Miller JL. The effectiveness of tumor necrosis factor a antibody (Infliximab) in treating recalcitrant psoriasis. Arch Dermatol 2002;138:644- 8. 120. Rongioletti F, Borenstein M, Kirsner R, et al. Erythrodermic, recalcitrant psoriasis: clinical resolution with infliximab. J Dermatol Treat 2003;14:222- 5. 121. Imamura S. Skin diseases first described in Japan. Clin Dermatol 1999;17:117- 26. Life-threatening erythroderma: diagnosing and treating the bred manQ 217