Erythrodermic psoriasis in adults

INTRODUCTION — Erythrodermic psoriasis is an uncommon, severe variant of psoriasis that is characterized by widespread erythema of the skin. Patients with this psoriasis subtype typically present with erythema involving more than 75 percent of the body surface area and associated scale, pustules, or exfoliation of the skin (picture 1A-C).

Recognition of this potentially life-threatening form of psoriasis is imperative. A detailed history and thorough evaluation of the patient are necessary to establish a diagnosis and rule out conditions that closely mimic erythrodermic psoriasis. (See "Erythroderma in adults" and "Erythroderma in children".)

The clinical manifestations, diagnosis, and management of erythrodermic psoriasis will be discussed here. Other variants of psoriasis are reviewed separately.

●(See "Psoriasis: Epidemiology, clinical manifestations, and diagnosis".)

●(See "Treatment of psoriasis in adults".)

●(See "Pustular psoriasis: Pathogenesis, clinical manifestations, and diagnosis".)

●(See "Pustular psoriasis: Management".)

●(See "Guttate psoriasis".)

●(See "Nail psoriasis".)

EPIDEMIOLOGY — Psoriasis is estimated to affect approximately 3 percent of the adult population in the United States [1]. There are several psoriasis subtypes, including chronic plaque, psoriatic arthritis, inverse, guttate, pustular, and erythrodermic variants. Erythrodermic psoriasis is the least common psoriasis subtype and occurs in less than 3 percent of patients [2]. Some experts have suggested that the distinction between generalized pustular and erythrodermic psoriasis is arbitrary given their frequent co-occurrence and overlapping clinical features. (See "Pustular psoriasis: Pathogenesis, clinical manifestations, and diagnosis" and 'Clinical manifestations' below.)

The age of onset of erythroderma is highly variable [3,4]. In a series of 50 patients with erythrodermic psoriasis, the average age of onset was 48 years [3]. There appears to be a slight predilection for males in adulthood [3]; however, detailed epidemiologic data for this condition are limited due to its rarity.

PATHOGENESIS — Similar to other psoriasis variants, erythrodermic psoriasis is the result of a complex interaction between the skin, environmental and genetic factors, and the immune system. Few studies have examined the molecular mechanisms driving the development of this disease variant, and the immunopathogenesis is not fully understood. (See "Pathophysiology of plaque psoriasis".)

A study evaluating the gene expression profiles of involved skin from patients with chronic plaque, inverse, and erythrodermic variants of psoriasis found similarities among these variants, suggesting a shared pathway for disease development [5]. More than 95 percent of the differentially expressed genes in erythrodermic psoriasis were also differentially expressed in plaque psoriasis. Differential expression of genes relating to the interleukin-17A signaling pathway accounted for the greatest amount of similarity between plaque and erythrodermic psoriasis. However, differences in the T helper cell (Th) populations and inflammatory cytokines isolated from the blood of patients with erythrodermic psoriasis compared with plaque psoriasis have also been described [6,7].

A study of 63 Chinese patients with erythrodermic psoriasis demonstrated that the prevalence of the primary plaque psoriasis genetic variant, HLA-Cw0602, may be less common in erythrodermic psoriasis patients (4 versus 16 percent in Chinese plaque psoriasis patients). The most common variants were HLA-C*0102 (34 percent), followed by HLA-C*0702 (18 percent) [8]. A mutation in CARD14, a known variant associated with pustular psoriasis, has also been detected in a pedigree with erythrodermic psoriasis [9].

A shared pathway for erythroderma is suggested based upon a study that compared the immunophenotypic features of psoriasis and atopic dermatitis. Although the study found significant differences in the Th1:Th2 ratio between chronic psoriasis and chronic atopic dermatitis, no differences in the Th1, Th2, Th17, and Th22 cell populations were observed between erythrodermic psoriasis and erythrodermic atopic dermatitis [10].

RISK FACTORS — The major risk factors for erythrodermic psoriasis are a personal or family history of psoriasis, medication exposure (particularly systemic glucocorticoids), and medical illness:

●History of psoriasis – The majority of patients with erythrodermic psoriasis have a known personal or family history of psoriasis [3]. Importantly, erythrodermic psoriasis may be the initial presentation of psoriasis.

●Medications – The most important medication-associated trigger of erythrodermic psoriasis is treatment with systemic glucocorticoids or the abrupt withdrawal of systemic antipsoriatic medications such as methotrexate and cyclosporine [3,11]. Erythrodermic psoriasis can also be triggered by an administration of antipsoriatic medications, such as oral and topical retinoids (eg, acitretin and tazarotene), methotrexate, cyclosporine, and overuse of topical corticosteroids (ie, use of more than 60 g per week of a high-potency topical corticosteroid) [3]. Other medications associated with the development of erythrodermic psoriasis include tumor necrosis factor (TNF)-alpha inhibitors [12,13], trimethoprim-sulfamethoxazole [14], bupropion [15], and pegylated interferon-alpha with ribavirin [16].

●Infection – Infections have been proposed as triggers for erythrodermic psoriasis. Patients with human immunodeficiency virus (HIV) infection have increased risk for erythrodermic psoriasis. The severity of psoriasis in HIV-infected patients positively correlates with the level of immunosuppression [17]. Cases of erythrodermic psoriasis following coronavirus disease 2019 (COVID-19) infection [18] and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination [19,20] have been reported.

Other factors that have been reported to trigger erythrodermic psoriasis include burns from phototherapy or photochemotherapy treatments [3], stress [3,21], alcohol consumption [3], and application of topical irritants (eg, coal tar, dithranol, and thiuram-containing rubber gloves ) [3,22,23]. Case reports suggest that hypocalcemia can trigger erythrodermic [24] or pustular forms of psoriasis [25,26]. However, the relationship between psoriasis and serum calcium levels is unclear.

CLINICAL MANIFESTATIONS — The hallmark of erythrodermic psoriasis is the development of widespread, confluent erythema of the skin (picture 1A-C). Erythema may develop rapidly (eg, over several days) or in a more gradual manner (eg, over several weeks). The percentage of body surface area involvement required for a patient to be considered erythrodermic is ambiguous; definitions range from 75 to more than 90 percent [3,27]. Scaling and exfoliation of the skin is common and usually develops several days after the onset of erythroderma (picture 2A-D). There may be associated palmoplantar keratoderma.

The skin is often painful and/or pruritic, particularly in areas with prominent scaling [28]. Photosensitivity also may be present. Associated extracutaneous findings may include fever, chills, malaise, tachycardia, arthralgias, and lymphadenopathy [3]. Laboratory abnormalities may include leukocytosis, eosinophilia, and anemia [3].

Erythrodermic psoriasis often exhibits pustules, similar to those occurring in pustular psoriasis (picture 3A-B). The pustules commonly involve the extremities. In a series of 50 patients with erythrodermic psoriasis, 14 patients (28 percent) had pustules [3]. Generalized pustular involvement has been reported and is representative of the overlap between erythrodermic psoriasis and generalized pustular psoriasis. There are no clinical features that reliably distinguish erythrodermic psoriasis with pustules from generalized pustular psoriasis. (See "Pustular psoriasis: Pathogenesis, clinical manifestations, and diagnosis".)

Associated nail disorders are common and range from pitting of the nail plate to more prominent nail dystrophy and/or separation of the nail from the nail bed (onycholysis). In a series of 50 patients with erythrodermic psoriasis, 39 (78 percent) had nail disease [3]. (See "Overview of nail disorders", section on 'Surface texture abnormalities' and "Overview of nail disorders", section on 'Defects of nail plate attachment/nail shedding'.)

DIAGNOSIS — A diagnosis of erythrodermic psoriasis should be considered in all patients presenting with erythroderma (ie, erythema involving at least 75 percent of the body surface area). The diagnosis is made based upon the recognition of features of psoriasis in the patient history, physical examination, and/or skin biopsy and the absence of features indicative of other causes of erythroderma. (See "Erythroderma in adults", section on 'Determining the underlying cause'.)

History and physical examination — A detailed history and full skin examination should be performed with particular attention to the following features:

●Personal or family history of psoriasis

●History of exposure to potential disease triggers (eg, recent systemic glucocorticoid therapy, abrupt withdrawal of antipsoriatic medications, or infection)

●Coexistence of other physical features of psoriasis (psoriatic plaques, arthralgias, or psoriatic nail disease)

When present, these features support a diagnosis of erythrodermic psoriasis; however, their absence does not exclude the diagnosis. Scale and exfoliation are common associated physical features. Pustules may or may not be present.

Features that suggest other causes of erythroderma are reviewed in detail separately. (See "Erythroderma in adults", section on 'Physical examination'.)

Skin biopsy — Performance of a skin biopsy is generally indicated. Skin biopsies can aid in excluding other causes of erythroderma and are often helpful in establishing a diagnosis of erythrodermic psoriasis in challenging cases. Features characteristic of psoriasis often are present.

In a retrospective review of biopsies obtained from 45 patients diagnosed with erythrodermic psoriasis, biopsies from 40 patients (88 percent) had histologic features consistent with psoriasis [29]. Histologic features of early psoriasis (eg, slight epidermal hyperplasia with a reduced or absent granular layer, focal parakeratosis, and mild spongiosis) were observed in more than one-half of patients from this study, whereas the remaining patients had features of a fully developed (eg, marked epidermal hyperplasia, total loss of the granular layer, and confluent parakeratosis) or regressing (eg, slight epidermal hyperplasia and a normal or thickened granular layer) psoriasis plaque. The most common histologic feature observed in this study was marked dilation and coiling of vessels within the papillary dermis [29]. (See "Erythroderma in adults", section on 'Skin biopsy and histopathologic examination'.)

Laboratory tests — While no serologic tests confirm the diagnosis of erythrodermic psoriasis, specific laboratory testing is frequently necessary to guide therapeutic management and exclude other causes of erythroderma. (See 'Differential diagnosis' below and "Erythroderma in adults", section on 'Laboratory and imaging tests'.)

DIFFERENTIAL DIAGNOSIS — Distinguishing erythrodermic psoriasis from other causes of erythroderma is necessary but often challenging. The patient history, physical findings, and biopsy results aid in narrowing the differential diagnosis (table 1A-B). (See "Erythroderma in adults", section on 'Etiology' and "Erythroderma in adults", section on 'Determining the underlying cause'.)

The exacerbation of a pre-existing skin disease is the most common etiology of erythroderma, accounting for more than one-half of all cases [30,31]. Psoriasis, atopic dermatitis, and seborrheic dermatitis are the most common associated cutaneous diseases. Knowledge of the clinical features prior to the onset of erythroderma is often helpful for diagnosis. Features suggestive of atopic dermatitis include an early age of onset, strong association with allergic rhinitis and asthma, prominent involvement of flexural surfaces, and disease worsening triggered by xerosis. Seborrheic dermatitis is typically characterized by dry or greasy flakes of skin, which involve the scalp, eyebrows, glabella, or external ear. (See "Atopic dermatitis (eczema): Pathogenesis, clinical manifestations, and diagnosis" and "Seborrheic dermatitis in adolescents and adults".)

Adverse drug reactions are another common cause of erythroderma, accounting for approximately 20 percent of patients presenting with erythroderma (table 2) [31]. Examples of other causes of erythroderma in the differential diagnosis of erythrodermic psoriasis include pityriasis rubra pilaris, cutaneous T cell lymphoma, paraneoplastic syndrome, graft-versus-host disease in patients with a history of allogenic bone marrow transplantation, immunobullous disorders, and infections. Erythroderma may also be idiopathic.

A list of causes of erythroderma is provided in a table (table 1A). The approach to determining the underlying cause of erythroderma is reviewed in detail separately. (See "Erythroderma in adults", section on 'Determining the underlying cause'.)

COMPLICATIONS — Potential complications of erythrodermic psoriasis include hemodynamic, thermoregulatory, and metabolic disturbances; electrolyte imbalances; infection; and acute respiratory distress syndrome:

●Hemodynamic, metabolic, and thermoregulatory disturbances — Erythroderma is the result of increased blood flow to the skin and cutaneous vasodilation, which account for the red appearance and warmth of the skin, respectively. This shunting of blood to the skin results in increased cardiac output and may lead to complications, such as peripheral edema, high-output cardiac failure, shock, or acute renal failure [32,33]. In addition, vasodilation and increased skin perfusion lead to fluid loss and subsequent electrolyte imbalances. Increased protein loss due to exfoliation of the skin has also been described [34], which may lead to hypoalbuminemia and contribute to the development of peripheral edema.

Patients with erythrodermic psoriasis also exhibit impaired thermoregulation and increased metabolic demands due to the rapid proliferation of epidermal cells [35]. The inability to properly regulate the body's temperature results in increased water loss and may lead to electrolyte abnormalities.

●Infection — Due to its exfoliative effect on large amounts of skin, erythrodermic psoriasis is associated with a defective skin barrier and increased portals for infection. Erythrodermic psoriasis patients are highly susceptible to skin infections, particularly staphylococcal septicemia [36].

●Acute respiratory distress syndrome (ARDS) — Several reports suggest that erythrodermic psoriasis can be complicated by ARDS [33,37,38]. The exact etiology of this complication is not known.

MANAGEMENT — Due to a paucity of high-quality studies, there is no consensus on the best treatment algorithm for erythrodermic psoriasis. Recommendations for management are primarily based upon small uncontrolled studies, case series, case reports, and the recommendations of psoriasis experts [11,27]. In general, management should involve:

●A pretreatment evaluation for disease complications and triggers

●Supportive care

●Prompt initiation of systemic antipsoriasis therapy

Pretreatment evaluation — The pretreatment evaluation should include:

●Vital signs, complete skin examination, and physical examination (to assess for signs of hemodynamic instability or infection)

●Complete blood count with differential

●Comprehensive metabolic panel (to assess fluid and electrolyte status and assess liver and kidney function)

●Viral and/or microbiologic studies (to rule out active infections in patients with suggestive clinical findings)

The need for additional testing is determined based upon these clinical and laboratory findings and any baseline laboratory tests required for the selected psoriasis therapy.

The pretreatment evaluation should also include an assessment for potential causative drugs (see 'Risk factors' above). Triggering drugs should be discontinued whenever feasible. In particular, discontinuation of systemic glucocorticoids can be challenging, as both the administration and withdrawal of systemic glucocorticoids can trigger erythrodermic psoriasis. A common approach is a very slow taper of the systemic glucocorticoid while the patient is receiving systemic psoriasis therapy. (See 'Systemic psoriasis therapy' below.)

Supportive care — Most patients with erythrodermic psoriasis require hospitalization for close clinical monitoring, replacement of fluids and electrolytes, and assistance with skin care. The decision to hospitalize is based upon disease severity and the presence of complications. Hemodynamically stable patients without rapidly progressing skin disease, significant fluid and electrolyte abnormalities, or concomitant infection are candidates for outpatient therapy provided they have adequate support at home for skin care, can return for frequent follow-up, and are in close proximity to a medical facility capable of managing erythrodermic patients. Patients with severe disease may require admission to the intensive care unit and often benefit from burn unit care where available.

Supportive measures useful for the management of these patients include:

●Monitoring of body temperature and hemodynamic status

●Fluid and electrolyte replacement as needed

●Nutritional support

●Treatment of associated infections

Skin-directed interventions that may improve skin discomfort and pruritus include [11]:

●Wet dressings

●Skin moisturization

●Oatmeal baths

●Topical corticosteroids (medium-potency topical corticosteroids for trunk and extremities, low-potency topical corticosteroids for facial and intertriginous areas)

Systemic psoriasis therapy — Initiation of a systemic antipsoriatic drug is essential for attaining disease control.

Overview — Antipsoriasis therapy should be initiated promptly. The most common drugs prescribed are cyclosporine, infliximab, acitretin, and methotrexate. Data on the comparative efficacy of these agents are lacking; therefore, factors such as the severity of disease, patient comorbidities, and drug availability influence the selection of treatment.

Cyclosporine is widely accepted as the treatment of choice for acute erythrodermic psoriasis based upon high efficacy, rapid onset of action, wide availability, and ease of administration. Patients with pre-existing renal disease or hypertension are less favorable candidates for cyclosporine therapy given the potential for cyclosporine-induced nephrotoxicity and hypertension. (See 'Cyclosporine' below.)

Infliximab also has a rapid onset of action and is an accepted alternative to cyclosporine for acute erythrodermic psoriasis. Downsides of infliximab include the requirement for intravenous infusion and the high cost of this therapy. (See 'Infliximab' below.)

Acitretin and methotrexate can be effective for erythrodermic psoriasis but are less frequently used as initial therapy because of a slower onset of action compared with cyclosporine and infliximab. Initial treatment with these agents is primarily reserved for patients with contraindications to cyclosporine and infliximab or with subacute disease presentations [11]. (See 'Acitretin' below and 'Methotrexate' below.)

Once disease control is achieved, patients treated with cyclosporine or infliximab are generally transitioned to other therapies, such as acitretin, methotrexate, or subcutaneously administered biologic therapies. Of note, limiting the duration of cyclosporine therapy to less than one year is recommended because of risk for cyclosporine-induced nephrotoxicity. Patients who initially received acitretin or methotrexate and achieved remission with these drugs can have the dose tapered to the lowest dose necessary to maintain improvement.

First-line therapies — Cyclosporine and infliximab are the preferred first-line therapies for erythrodermic psoriasis. However, data on the efficacy of these therapies are limited.

Cyclosporine — Oral cyclosporine may lead to significant improvement within the first few weeks of treatment:

●Efficacy – In an uncontrolled study of 33 adults with erythrodermic psoriasis given cyclosporine (maximum initial dose of 5 mg/kg per day), complete remission (total disappearance of erythema and desquamation) occurred within one year in 22 patients (67 percent), with a median time to remission of two to four months [39]. An additional 27 percent of patients achieved marked improvement, with at least a 70 percent reduction in the involved skin area compared with baseline.

●Administration – Cyclosporine is given orally in doses of 3 to 5 mg/kg per day. For patients with severe disease, 5 mg/kg per day typically is given as initial treatment. Significant improvement often occurs within the first month [39]. Once remission is achieved, the dose is tapered as tolerated over a few months.

Risk for cyclosporine-induced nephrotoxicity limits the duration of treatment. Treatment with cyclosporine should not exceed one year and should be discontinued after three to four months in patients unresponsive to a dose of 5 mg/kg per day [11,40].

In addition to nephrotoxicity, important adverse effects of cyclosporine include drug interactions, uncontrolled hypertension, and increased risk for infections and malignancy. Use of cyclosporine in patients with pre-existing renal disease or hypertension should be considered carefully. Such patients may benefit from alternative therapies. Adverse effects of cyclosporine are reviewed in detail separately. (See "Pharmacology of cyclosporine and tacrolimus", section on 'Side effects' and "Cyclosporine and tacrolimus nephrotoxicity".)

Baseline and periodic monitoring of blood pressure and laboratory tests is indicated for cyclosporine therapy. For additional information, refer to the drug interactions program included within UpToDate.

Infliximab — Infliximab is a common alternative to cyclosporine for acute erythrodermic psoriasis [11,27]. Like cyclosporine, infliximab has a rapid onset of action:

●Efficacy – In a retrospective study that included 24 treatment courses of infliximab in 20 patients with erythrodermic psoriasis, 50 percent of patients given infliximab achieved at least a 50 percent improvement in either the Psoriasis Area and Severity Index score or body surface area involvement by four weeks [41]. Good responses to infliximab have also been documented in a small uncontrolled study and case reports [42-45].

●Administration – Infliximab is given as the standard regimen recommended for psoriasis (5 mg/kg at zero, two, and six weeks, followed by 5 mg/kg every eight weeks). Marked improvement can occur within the first several weeks of treatment. If there is no treatment response observed within four to six weeks, significant benefit may be less likely to occur. In this scenario, we would transition the patient to cyclosporine or another treatment.

Potential serious side effects of infliximab include infusion reactions, increased risk for infection, exacerbations of heart failure, demyelinating disease, and malignancy. Infliximab is contraindicated in patients with active infections and should be used cautiously in patients with neurologic disorders (eg, multiple sclerosis), heart failure, or a history of malignancy. Screening for tuberculosis is recommended prior to infliximab treatment. The adverse effects of infliximab are reviewed in detail separately. (See "Tumor necrosis factor-alpha inhibitors: An overview of adverse effects".)

Alternative first-line therapies — Acitretin and methotrexate may be effective for erythrodermic psoriasis but exhibit a slower onset of action compared with cyclosporine and infliximab. Thus, initial treatment with these agents is typically reserved for patients who cannot be treated with cyclosporine or infliximab or who have subacute disease presentations.

Acitretin — Acitretin for erythrodermic psoriasis is typically given in doses of 25 to 50 mg per day. The maximal effect of acitretin often is not evident for three to six months [40]. If at least partial improvement does not occur within three months, we discontinue treatment.

Although acitretin is a common treatment for psoriasis, data on efficacy for the erythrodermic variant are limited. In a 1988 review of data from 12 open or double-blind clinical studies evaluating acitretin for psoriasis, improvement assessed as at least marked or good occurred in five of the six erythrodermic patients treated with acitretin [46].

Acitretin can cause hyperlipidemia and hepatotoxicity, and some patients are unable to tolerate the drug due to side effects such as paresthesias, arthralgias, cheilitis, and xerostomia. Acitretin is teratogenic and should be avoided in pregnant women and females of child-bearing potential who intend to become pregnant within three years after discontinuation of treatment. For additional information on side effects and monitoring, refer to the drug interactions program included within UpToDate.

Methotrexate — Methotrexate is typically given on a weekly basis; adults with erythrodermic psoriasis are typically treated with a single weekly dose of 7.5 to 25 mg per day. Folic acid supplementation (1 mg per day) should be given in conjunction with methotrexate therapy.

Initial signs of therapeutic benefit are often evident within the first four weeks of treatment. If there are no signs of response within four to six weeks, we discontinue methotrexate treatment.

Similar to acitretin, efficacy data for erythrodermic psoriasis are limited. In a retrospective review of 157 psoriasis patients treated with methotrexate, a response rated as a "moderate" or "good" clinical response was observed in 34 of 36 erythrodermic patients [47].

Gastrointestinal distress is a common side effect of methotrexate. Potential serious adverse effects of methotrexate include hepatotoxicity, myelosuppression, and pulmonary toxicity. Methotrexate is teratogenic and is contraindicated during pregnancy. The drug is also contraindicated in patients with active infections, malignancy, bone marrow suppression, or pre-existing kidney or liver disease. Close monitoring for hematologic and hepatic side effects is essential during methotrexate therapy. For additional information on side effects and monitoring, refer to the drug interactions program included within UpToDate.

Other therapies — Limited data suggest that etanercept, adalimumab, and other biologic therapies can be effective for erythrodermic psoriasis. In a multicenter, retrospective review of 24 erythrodermic psoriasis patients treated with various tumor necrosis factor (TNF)-alpha inhibitors, the efficacy of etanercept and adalimumab was comparable with infliximab [41]. However, the onset of action of these agents is slower than for cyclosporine or infliximab [27,48], making them less preferable therapies for erythrodermic psoriasis.

Small, open-label studies and case reports provide preliminary support for the use of newer biologic medications for the treatment of erythrodermic psoriasis, including ustekinumab [49], ixekizumab [50-52], secukinumab [53,54], guselkumab [55], brodalumab [56], risankizumab [57], and golimumab [58], as well as the small molecule drug apremilast [59-61]. While these therapies represent a group of medications likely to be effective in the treatment of erythrodermic psoriasis, subsequent, larger studies are necessary prior to a recommendation for the routine use of these therapies. That said, the rapid onset of interleukin (IL) 17 inhibitors and their apparent efficacy in open-label studies of patients with generalized pustular psoriasis make them attractive alternatives to anti-TNF or anti-IL-12/23 inhibitors. (See "Pustular psoriasis: Management".)

Severe, refractory disease — Combinations of systemic therapies may be appropriate in severe or refractory cases of erythrodermic psoriasis (eg, infliximab with methotrexate or acitretin). However, evidence for this approach is based largely on case reports or small case series [44,62].

The potential benefit of wet dressings with mid-potency topical corticosteroids (eg, triamcinolone 0.1% cream) should not be discounted in patients with severe disease. Use in combination with systemic treatments aids in the management of patient symptoms and may promote disease resolution. (See 'Supportive care' above.)

Contraindicated therapies — The use of systemic glucocorticoids for erythrodermic psoriasis is strongly discouraged due to the ability of systemic glucocorticoids to trigger severe psoriasis flares. Phototherapy is also generally avoided in erythrodermic patients given the photosensitivity of these patients, though this recommendation is not absolute. (See 'HIV-infected patients' below.)

Special population — The approach to the treatment of erythrodermic psoriasis differs in HIV-infected individuals.

HIV-infected patients — Patients infected with HIV are at increased risk for psoriasis, including less common variants like erythrodermic psoriasis [63]. HIV-associated psoriasis tends to follow a more severe disease course and is also frequently refractory to conventional antipsoriatic therapies, which primarily target the T cell-mediated immune response. Therefore, the management of erythrodermic psoriasis in HIV-infected patients represents a challenging clinical scenario based on their relative immunosuppression, susceptibility for infections, and severity of symptoms.

We agree with the Medical Board of the National Psoriasis Foundation, which recommends antiretroviral therapy or ultraviolet (UV) phototherapy as first-line treatments for erythrodermic psoriasis in HIV-positive patients [64]. The potential benefit of antiretroviral therapy for the treatment of erythrodermic psoriasis is highlighted in a report of a patient who experienced rapid clearing of his clinical symptoms within two weeks of initiating antiretroviral therapy despite previous failure to respond to cyclosporine, acitretin, systemic glucocorticoids, and TNF-alpha inhibitors [65].

Acitretin is recommended as second-line treatment. The use of other conventional psoriasis medications, such as cyclosporine, methotrexate, and TNF-alpha inhibitors, is based on limited clinical evidence, and they should be used with caution due to the increased risk of opportunistic infections and bone marrow toxicity [66,67]. (See 'Acitretin' above and "Treatment selection for moderate to severe plaque psoriasis in special populations", section on 'HIV infection'.)

PROGNOSIS — Overall, the majority of erythrodermic psoriasis patients respond to one or more available treatment options. However, prognostic data for this condition are deficient and highly variable, with mortality rates ranging anywhere from 9 to 64 percent [3,28]. Most deaths associated with erythrodermic psoriasis are attributed to bacterial infections, such as pneumonia or staphylococcal septicemia [36].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Psoriasis".)

SUMMARY AND RECOMMENDATIONS

●Disease overview – Erythrodermic psoriasis is a potentially life-threatening, rare subtype of psoriasis characterized by erythema involving more than 75 percent of the body surface area and the presence of scaling, exfoliation/desquamation, and/or pustules of the skin (picture 1A-C). Systemic signs and symptoms, including fever, chills, malaise, tachycardia, arthralgias, eosinophilia, anemia, lymphadenopathy, and photosensitivity, are commonly associated with erythrodermic psoriasis. (See 'Clinical manifestations' above.)

●Risk factors – More than one-half of all cases of erythrodermic psoriasis are attributed to the exacerbation of pre-existing psoriasis. Important triggers include medications (eg, the withdrawal of oral or topical corticosteroids and the discontinuation or abrupt withdrawal of antipsoriatic therapies), infections, alcohol consumption, and stress. (See 'Risk factors' above.)

●Diagnosis – Differentiating erythrodermic psoriasis from other causes of erythroderma is essential but frequently challenging. The diagnosis is made based upon the recognition of features of psoriasis in the patient history, physical examination, and/or skin biopsy and the absence of features indicative of other causes of erythroderma. (See 'Diagnosis' above.)

●Complications – Complications of erythrodermic psoriasis include hemodynamic and metabolic disturbances, increased metabolic requirements, a defective skin barrier, impaired thermoregulation, acute respiratory distress syndrome (ARDS), and susceptibility to skin infections, specifically staphylococcal septicemia. (See 'Complications' above.)

●Supportive care – Inpatient hospitalization may be necessary for close clinical evaluation, including hemodynamic monitoring, replacement of fluids and electrolytes, and assistance with the application of wet dressings. Patients with severe disease may require admission to the intensive care unit and often benefit from burn unit care where available. (See 'Supportive care' above.)

●Treatment – Treatment guidelines for erythrodermic psoriasis are based on small uncontrolled studies, case series, case reports, and expert opinion. Factors such as severity of disease, patient comorbidities, and drug availability influence the selection of treatment (see 'Systemic psoriasis therapy' above):

•First-line therapy – We suggest cyclosporine or infliximab as first-line therapy for erythrodermic psoriasis based upon the rapid onset of action of these therapies (Grade 2C). Acitretin and methotrexate are also first-line treatment options, though a slower onset of action makes them less preferable agents. (See 'Systemic psoriasis therapy' above.)

•Other therapies – Additional treatments that may be effective include other tumor necrosis factor (TNF)-alpha inhibitors (eg, etanercept, golimumab, and adalimumab), other biologic medications (eg, interleukin [IL] 12/23, IL-17A, IL-17 receptor, and IL-23 inhibitors), and antipsoriatic small molecules (eg, apremilast) used in the treatment of other psoriasis subtypes. (See 'Other therapies' above.)