key: cord-0039307-f7xio95i authors: Harper-Kirksey, Katrina title: Erythroderma date: 2018-09-12 journal: Life-Threatening Rashes DOI: 10.1007/978-3-319-75623-3_19 sha: 367452896b3c292ca142ca53dcbcbc25a49ea417 doc_id: 39307 cord_uid: f7xio95i Erythroderma, often described as generalized exfoliative dermatitis, is a condition in which erythema involves greater than 90% of the body surface, often as a result of an underlying inflammatory skin condition, which can result in a variety of systemic manifestations and potentially lead to life-threatening complications. Erythroderma is a severe and potentially life-threatening dermatitis described as an intense and widespread erythema typically involving greater than 90% of the body surface area, with a variable degree of exfoliative skin scaling (see Figs. 19 .1 and 19.2) [1, 2] . It is a manifestation of a wide range of cutaneous and systemic diseases including infection, malignancy, and drug hypersensitivity reactions [3] . There are numerous systemic and cutaneous diseases known to be associated with erythroderma (Tables 19.1 and 19 .3). The most common trigger of erythroderma is an exacerbation of an underlying dermatitis, most commonly psoriasis ( Fig. 19 .3) (23%), atopic dermatitis, and contact dermatitis [4] [5] [6] [7] . Drug reaction is another important cause of erythroderma, implicated in 20% of cases, with at least 135 drugs suspected as potential causative agents [5] [6] [7] [8] 10] . A common malignancy associated with erythroderma is cutaneous T-cell lymphoma (CTCL) [3, 7, 9] . Idiopathic erythroderma, where no cause can be elucidated despite thorough serial investigations, occurs in approximately 30% of cases. "Red man's syndrome" associated with rapid vancomycin infusion is considered to be an example of idiopathic erythroderma [3-5, 8, 10, 11] . Because erythroderma is often associated with scaling and extensive erythema, it is often difficult to discern the typical features characteristic of the preexisting, underlying condition. For this reason, diagnosis and management strategies can be challenging [1, 2] . Erythroderma is thought to be mediated by a complicated process of inflammatory cell interactions, resulting in a dramatic turnover of epidermal cells [12] . It is a rare condition, with an incidence rate of approximately 1 per 100,000 adults [13] . Erythroderma is rare in children and occurs at an average age of 42-61 years [14] . When age of onset is less than 40 years, the condition is typically a result of atopic dermatitis, seborrheic dermatitis, staphylococcal scalded skin syndrome, or a hereditary ichthyosis [14, 15] . It is more common in males and has no racial predilection [3-7, 9, 16] . The typical presentation of erythroderma is characterized by erythematous patches which progressively increase in size and coalesce to cover most of the body's surface, with occasional islands of sparing [17] . Scaling can occur as large sheets or small flakes and generally erupt 2-6 days after the onset of erythema. Pruritus is common and is most severe in patients with atopic dermatitis and Sezary syndrome [50] . The skin may feel leathery secondary to excessive scratching and there may be eyelid and periorbital involvement [18] . Especially in chronic conditions, patches of hypopigmentation can be observed, and hair and nails may shed [19] . Nails may also become ridged, thickened, and brittle [9, 17, 20, 21] . Individuals with long-standing erythroderma may present with cachexia, vitiligo, diffuse alopecia (see Fig. 19 .5), and thickened palms and soles (Table 19. 2) [18, 22] . Systemic symptoms related to erythroderma itself or to the primary disease can be observed. Many of these features can lead to serious sequelae and are discussed further in the complications section. Patients often are unwell appearing and report chills, fever, fatigue, and malaise. Lymphadenopathy and (rarely) splenomegaly can be observed. Hepatomegaly is seen in 1/3 of cases and is most common in drug-induced erythroderma [7, 22] . Significant protein loss exceeding 9 g/ m 2 body surface per day as a consequence of skin exfoliation can lead to hypoalbuminemia, edema, and muscle wasting [12] . As a result, patients may experience loss in temperature regulation and up to 50% of patients develop pretibial and pedal edema [2, 3] . When erythroderma occurs secondary to drug reaction, eosinophilia can be observed along with systemic symptoms characteristic of DRESS (drug reaction and systemic symptoms; see Chap. 20) [2] . Erythroderma may develop rapidly over hours to days or more gradually over weeks to month (see Table 19 .4) [22] . Patients may initially present as medically stable or with life-threatening complications [3] . The duration of erythroderma is highly variable and is determined by the underlying cause. Erythroderma as a result of primary skin disease is typically a gradual course with a median duration of 10 months but can go on to last years [7] . The disease evolves more rapidly when it is a result of drug hypersensitivity reaction, lymphoma, or leukemia. In the setting of systemic disease, symptoms may persist from weeks to years -dependent on the course of the underlying disorder. Conversely, in the case of drug-induced erythroderma, resolution of disease can occur in as little as 2-6 weeks after discontinuation of the offending agent [3] . Patients with DRESS, however, may take longer to recover -over weeks to months with possible relapse (see Chap. 20). The diagnosis of erythroderma is difficult given it is usually a manifestation of an underlying diagnosis or exacerbation of primary disorder (Table 19 .5). Additionally, the characteristic physical findings of erythroderma generally obscure underlying disease features. As the list of causative factors of erythroderma continues to expand, it becomes more difficult to pinpoint the precipitating diagnosis [22] . Because of this, a thorough history of presenting illness is of utmost importance in diagnosing erythroderma [23] . Patients must be asked about all medications, preexisting medical conditions, allergies, and previous diagnoses of rash and skin disorders [7, 22] . Physical examination is crucial in attempts to detect an underlying etiology as well as to evaluate for systemic involvement and potential complications (i.e., organomegaly, lymphadenopathy, peripheral edema, infection, heart failure, and potential respiratory compromise) [7, 18, 24] . Following a detailed history and physical, a skin biopsy, laboratory studies, imaging, and histology may useful adjuncts to derive a definitive diagnosis and exclude clinical mimics (see Fig. 19.6) . These ancillary studies are often nonspecific, although with repeat testing the diagnosis may become apparent over time (Table 19 .6) [11, 15, 16] . Erythroderma is a dermatologic emergency which requires a dermatology consultation and hospital admission for severe cases to avoid potentially catastrophic complications. The principle management consists of discontinuation of all offending medications, maintaining skin moisture and integrity (through aggressive wound care), adequate hydration and nutrition, electrolyte repletion, and antibiotics for secondary infection (Table 19 .7). Erythroderma as an isolated process will persist until the underlying condition is addressed, and the primary etiology may impact disease course and management options. Therefore, once the underlying diagnosis is established,targeted therapy should be administered promptly (Table 19.8) . If a cause can be identified, then specific treatment should be initiated. Notably, systemic steroid should be avoided in psoriasis and staphylococcal scalded skin syndrome. Consider if cause unknown although tend to be nonspecific Repeated biopsies may be necessary Skin scrapings may show hyphae or mites Imaging [22] If cause is unknown, imaging may be performed as a survey for occult malignancy Chest radiograph can identify infections, inflammatory disorders such as sarcoidosis with hilar lymphadenopathy, and congestive heart failure Cultures/PCR Evaluation for suprainfection, fungal infections, herpes simplex virus, and varicella zoster virus Histological [27] [28] [29] [30] In all comers, hyperkeratosis, acanthosis, spongiosis, and perivascular inflammatory infiltrate are frequent findings in general May otherwise be nonspecific Immunofluorescence [22, 31] Of benefit in autoimmune blistering disease or connective tissue disease (i.e., immunoglobulins at the dermal-epidermal junction) [3, 22, 32] Topical corticosteroids and oral antihistamines Oatmeal baths or warm wet compresses (no more than a quarter of the body at a time) Bland emollients or petrolatum for patient comfort Infections Blood cultures Broad-spectrum antibiotic coverage (to include MRSA) Antiviral medications where appropriate [46] Extracorporeal photochemotherapy Systemic retinoids Interferon Pityriasis rubra pilaris (PRP) [22, 47] Systemic retinoids as first line Topical steroids as adjunct to palms, soles, face, skin folds, and extremities May consider methotrexate, TNF-alpha inhibitors, cyclosporine, and azathioprine Drug induced [2, 7, 35] Discontinue causative agents Short-course oral steroids or pulse intravenous IV steroid therapy Idiopathic erythroderma [1, 5, 9, 11] Low to mid-potency topical corticosteroids Oral antihistamines In refractory cases: systemic corticosteroids While the physiologic demands of erythroderma are tolerated by many patients, those at the extremes of age and patients with multiple comorbidities may suffer life-threatening consequences (see Table 19 .9). The shunting of blood through the skin due to peripheral vasodilation can result in high-output heart failure [3] . These patients can present with tachycardia and pulmonary edema. Increased skin perfusion also results in temperature dysregulation and fluid and electrolyte imbalance. Exfoliation and protein loss result in edema and leave patient's susceptible to secondary infections [12] . Acute respiratory distress syndrome (ARDS) is also a common complication. End-organ damage may develop such as hepatitis, myocarditis, and/or interstitial nephritis [2] . Mortality rates range between 4 and 64% depending on the patient population [7, 22] . In the majority of cases, erythroderma results from an underlying condition and cannot itself be prevented [22] . Individuals who develop erythroderma as a result of drug hypersensitivity should be instructed to avoid the offending agent in the future. Erythroderma as a result of underlying inflammatory skin condition will usually abate with treatment but may recur at any time. Idiopathic erythroderma is characterized by a more unpredictable course. Overall, prognosis of erythroderma is dependent on the underlying cause and is generally favorable if the underlying disease can be effectively treated [48] [49] [50] . Acquired erythroderma in adults: a clinical and prognostic study The color atlas of family medicine Life-threatening erythroderma: diagnosing and treating the "red man Erythroderma: a clinico-etiologic study of 90 cases Erythroderma: a clinical study of 97 cases Erythroderma in adults: a report of 80 cases Fitzpatrick's dermatology in general medicine Dapsone hypersensitivity syndrome in non-leprosy patients: a retrospective study of its incidence in a tertiary referral center in Taiwan Erythroderma: a clinical and prognostic study Idiopathic erythroderma: a follow-up study of 28 patients The red man syndrome. Exfoliative dermatitis of unknown etiology: a description and follow-up of 38 patients Quantitative estimation and recommendations for supplementation of protein lost through scaling in exfoliative dermatitis The incidence of erythroderma: a survey among all dermatologists in the Netherlands Neonatal and infantile erythrodermas A clinical and follow-up study of 102 patients, with special emphasis on survival Erythroderma/exfoliative dermatitis: a synopsis The spectrum of hair loss in patients with mycosis fungoides and Sézary syndrome Pityriasis rubra pilaris: a review of diagnosis and treatment Treatment of erythrodermic psoriasis: from the medical board of the National Psoriasis Foundation A review of the diagnosis and Management of Erythroderma (generalized red skin). In: Advances in skin and wound care: Woltkers Kluwer Health Erythroderma: a clinical-etiological study of 82 cases Erythrodermic atopic dermatitis with late onset casepresentation A clinicopathological study of 56 cases Pityriasis rubra pilaris The role of histological presentation in erythroderma Histopathologic diagnosis of lymphomatous versus inflammatory erythroderma: a morphologic and phenotypic study on 47 skin biopsies The specificity of histopathology in erythroderma Erythroderma: analysis of 247 cases Combining biologic therapies with other systemic treatments in psoriasis: evidence-based, best-practice recommendations from the medical Board of the National Psoriasis Foundation Erythroderma: a dermatologic emergency New era of biologic therapeutics in atopic dermatitis Tokyo: Hokkaido University Press/ Nakayama Shoten Atopic dermatitis in older patients: particular points New and emerging trends in the treatment of atopic dermatitis Successful treatment of psoriasis and psoriatic arthritis with etanercept and methotrexate in a patient newly unresponsive to infliximab Addition of low-dose methotrexate to infliximab in the treatment of a patient with severe, recalcitrant pustular psoriasis A review of the clinical variants and the management of psoriasis Erythroderma in the era of biological therapies Results of a prospective phase II trial with oral low dose bexarotene plus photochemotherapy (PUVA) in refractory and/or relapsed patients with mycosis fungoides Polish lymphoma research group experience with bexarotene in the treatment of cutaneous T-cell lymphoma Cutaneous T cell lymphoma: an update on pathogenesis and systemic therapy Diagnosis and management of mycosis fungoides update on diagnosis, risk-stratification, and management Review of the treatment of mycosis fungoides and Sézary syndrome: a stagebased approach Pityriasis rubra pilaris Erythrodermic psoriasis. Precipitating factors, course, and prognosis in 50 patients Sézary syndrome: a study of 176 patients at Mayo Clinic Prognostic factors in erythrodermic mycosis fungoides and the Sezary syndrome Biological products for the treatment of psoriasis: therapeutic targets, pharmacodynamics and disease-drug-drug interaction implications Use of biologic agents in combination with other therapies for the treatment of psoriasis Erythroderma in the era of biological therapies Generalized Exfoliative Dermatitis) clinical presentation