ERITRODERMIA PSORIASICA PDF

The pathogenesis of EP is not well understood; however, several studies suggest that the disease is associated with a predominantly T helper 2 Th2 phenotype. Given the morbidity and potential mortality associated with the condition, there is a need for a better understanding of its pathophysiology. In , the medical board of the US National Psoriasis Foundation published consensus guidelines advocating the use of cyclosporine or infliximab as first-line therapy in unstable cases, with acitretin and methotrexate reserved for more stable cases. Since the time of that publication, additional information regarding the efficacy of newer agents has emerged.

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The pathogenesis of EP is not well understood; however, several studies suggest that the disease is associated with a predominantly T helper 2 Th2 phenotype. Given the morbidity and potential mortality associated with the condition, there is a need for a better understanding of its pathophysiology. In , the medical board of the US National Psoriasis Foundation published consensus guidelines advocating the use of cyclosporine or infliximab as first-line therapy in unstable cases, with acitretin and methotrexate reserved for more stable cases.

Since the time of that publication, additional information regarding the efficacy of newer agents has emerged. We review the latest data with regard to the treatment of EP, which includes biologic therapies such as ustekinumab and ixekizumab. Download video file. EP presents with generalized cutaneous findings such as erythema, edema, pruritus, ill-defined psoriatic plaques, scaling, hair loss, and occasionally exudative lesions and palmoplantar or diffuse desquamation.

Additional histological features of EP include some features of classical psoriasis, including parakeratosis, acanthosis, spongiosis, Munro micro-abscesses, and occasional apoptotic keratinocytes.

Although the aforementioned parameters are sufficient to make a diagnosis of EP, it is important to note that the disease can be categorized further into two general clinical subtypes. The first is characterized by the presence of psoriatic plaques with gradual additional development of a generalized erythroderma in which the psoriatic plaques remain differentiable from the erythroderma. The disease course is relatively stable and prognosis is favorable in this form of EP. The second subtype, which is more commonly seen in the setting of psoriatic arthritis, is often characterized by rapid whole body erythema and lack of demarcated psoriatic plaques.

The disease course is relatively unstable and is more likely to be associated with abnormal vital signs and laboratory values. Accordingly, prognosis is not as favorable and there is appreciable mortality. The first clinical subtype is often associated with a more chronic and prolonged course, while the second subtype is more likely to be acute, rapidly progressive, and relapsing. Because there is such a large list of possible EP triggers, it is sometimes difficult to differentiate the trigger from post-EP-related comorbidities.

Therefore, it is important to be aware that EP patients commonly acquire superinfections of the skin and blood with Staphylococcus aureus and Group A Streptococcus that may lead an unaware clinician to conclude that the infection was a trigger to the EP. In , scientists demonstrated a statistically significant increase in serum immunoglobulin E in EP compared to PV patients.

Interestingly, a previous study had shown that IL-4, the signature Th2-inducing cytokine, was safe and effective in the treatment of plaque-type psoriasis. The authors attributed its efficacy to the induction of the Th2 pathway in skin-infiltrating lymphocytes.

Given their established importance in PV, the contribution of Th17 cells to EP pathogenesis has also recently been investigated. The authors also observed significant immunologic overlap of Th17 cells in EP and erythrodermic atopic dermatitis. Initial management of EP must include correction of any fluid, protein, and electrolyte abnormalities; a nutritional assessment; prophylaxis against hypothermia; and treatment of any secondary infections.

Sepsis caused by skin pathogens, most commonly Staphylococcus aureus , is a particularly severe and potentially fatal complication that has been reported. In , the medical board of the US National Psoriasis Foundation published consensus guidelines regarding the appropriate management of EP once initial stabilizing measures have been undertaken.

They advocate the use of cyclosporine or infliximab as first-line therapy in acute and unstable cases. For more stable cases, on the other hand, acitretin and methotrexate are the preferred agents. Second-line options include etanercept and combination therapy.

Later, we review the latest data with regard to the treatment of EP. With the development of more potent and targeted therapies, the use of topicals in EP has become less common. Nevertheless, they may be helpful for nontoxic patients or as adjunct therapy for recalcitrant lesions in more severe disease. A case series of two patients treated with twice-daily topical betamethasone dipropionate ointment, colloidal oatmeal baths, and total body occlusion reported significant skin clearing within three to four hospital days.

The vitamin D analogs comprise a rising first-line therapy for mild-to-moderate plaque psoriasis given their ability to abrogate skin cell proliferation, enhance skin cell differentiation, and modulate immunologic factors that are involved in disease etiology.

Phototherapy is an effective, first-line treatment for moderate-to-severe plaque psoriasis that works by inhibiting keratinocyte proliferation, promoting keratinocyte apoptosis, and dampening the inflammatory Th1 and Th17 pathways. Etretinate and its active metabolite, acitretin, are effective systemic treatments for moderate-to-severe psoriasis and other hyperkeratotic disorders Table 3.

They function to normalize keratinocyte proliferation and differentiation, regulate sebaceous gland activity, and modulate local inflammatory responses. Studies examining conventional systemic agents as monotherapy in erythrodermic psoriasis. According to expert consensus, acitretin is considered a high-priority agent for stable cases of EP as it has a relatively slower onset of action.

After 1 month of treatment, the patient had near-complete resolution of his lesions and remained clear at 2-month follow-up. It is important to note, though, that this patient was significantly overweight and may have been underdosed. The second-generation retinoids have also been used in combination with other systemic agents, such as cyclosporine and infliximab. Three patients treated with 0. Interestingly, there are also case reports describing acitretin- and etretinate-induced EP, which ultimately resolved after the drug was discontinued and replaced with cyclosporine.

Systemic retinoids have also exhibited reduced efficacy in the context of low serum albumin levels as it is thought that transport proteins such as albumin are necessary for the migration of acitretin into peripheral tissues. Methotrexate is an immunosuppressive drug that inhibits the enzyme dihydrofolate reductase. Oral systemic therapy with methotrexate is a first-line option for patients with plaque psoriasis who have inadequate control on topicals alone. Like acitretin, methotrexate also has a slower onset of action and is considered a high-priority agent for more stable cases of EP.

It is either taken orally or administered as a once-weekly injection, commonly 5—7. Long-term use of methotrexate may increase the risk of hepatotoxicity, hepatic fibrosis, and bone marrow suppression. A retrospective analysis of 21 patients with severe psoriasis or EP treated with an initial dose of 5—7. Mean remission period lasted 14 months. One of these patients was even continued on maintenance therapy for 2 years with lasting remission.

Both patients began to experience significant skin clearing within a few weeks. Notably, one patient was also receiving concomitant compound glycyrrhizin, an agent that is thought to block production of IL Cyclosporine is an immunosuppressive agent that blocks IL-2 transcription, thereby impairing the growth and activity of T-cells. Cyclosporine is approved by the US Food and Drug Administration for the treatment of severe plaque psoriasis in immunocompetent adults.

Case series and reports advocate the use of cyclosporine in the treatment of EP at doses of 1. Mycophenolate mofetil is another immune suppressant that selectively inhibits activated lymphocytes.

It has efficacy as a monotherapy for moderate-to-severe psoriasis in several case reports, small clinical studies, and a randomized controlled trial. Biologic therapy encompasses an emerging category of drugs that target specific cytokines of the immune system. Given their enhanced selectivity, these agents are a promising alternative to the conventional immunosuppressants, such as methotrexate and cyclosporine.

Etanercept is administered subcutaneously once to twice weekly maximum individual dose of 50 mg. Clearance, defined as PASI90, was obtained in two of six Etanercept has also been used concomitantly with methotrexate in a pediatric patient presenting with recalcitrant EP.

Her erythrodermic manifestations gradually subsided over a 3-month period and were not noted to reappear throughout 2-year follow-up. It is administered subcutaneously at an initial dose of 80 mg at week 0, followed by 40 mg every other week starting at week 1. Lastly, a complicated EP patient with concomitant hepatitis C virus infection and hemophilia remarkably achieved remission at week 3 of treatment with adalimumab. This interaction results in decreased epidermal T-cell infiltration.

Therefore, expert consensus considers the drug an additional first-line option for unstable cases of EP. Several case reports and series, as well as one multicenter clinical trial, support the use of infliximab as a monotherapy in EP. However, a couple of case reports suggest that infliximab may lose efficacy after successive infusions. In these patients, no further reduction in PASI was appreciated after 14 weeks and 30 weeks of treatment.

No significant adverse events were reported throughout the duration of therapy. Ustekinumab is a fully human monoclonal antibody that binds the p40 subunit of both IL and IL These two cytokines are involved in the pathogenesis of psoriasis by stimulating the Th1 and Th17 inflammatory pathways, respectively.

Ustekinumab is approved for the treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis and is administered subcutaneously.

The injections are administered at weeks 0 and 4 and then every 12 weeks thereafter. Ixekizumab is a humanized IgG4 monoclonal antibody that inhibits ILA, an inflammatory cytokine of the Th17 pathway that has been implicated in the pathogenesis of psoriasis.

The drug has also more recently been tested in a Phase III, multicenter, single-arm, open-label study of eight EP patients.

All subjects received a mg subcutaneous injection at week 0, 80 mg every 2 weeks through week 12, and 80 mg every 4 weeks through week The authors reported that at week 12, eight patients Panitumumab is a human monoclonal antibody targeting the epidermal growth factor receptor EGFR.

A patient with recalcitrant EP who failed treatment with calcipotriol ointment, topical steroids, etretinate, and psoralen plus ultraviolet A showed dramatic improvement within 10 days of treatment with panitumumab. His achieved results lasted at least 6 months after the initiation of therapy. Alefacept and efalizumab are two biologics previously approved by the Food and Drug Administration for psoriasis that are no longer available. A case series following two patients has been published regarding the use of alefacept in EP.

Both patients had recalcitrant psoriasis that responded completely to a full course of alefacept. One of the patients achieved this response by 14 weeks, yet flared back to baseline 2 weeks after discontinuing treatment. The second patient was on a concomitant week cyclosporine taper during which he maintained good results. EP is a rare and severe disorder that is distinct from PV.

Although the exact pathogenesis of EP is not fully understood, it is thought to involve a complex interplay of the Th1, Th2, and Th17 inflammatory pathways. Functional studies involving these cytokines may help clarify their roles in the pathogenesis of EP. Given the morbidity and potential mortality associated with the condition, there is a need for a better understanding of EP pathophysiology.

Often patients require supportive measures that address electrolyte abnormalities, nutritional status, impaired thermoregulation, and underlying infection, among other things. Furthermore, potential septic and thromboembolic complications justify close surveillance of patients and often also hospitalization. Severe and unstable cases of EP benefit from rapidly acting agents, such as cyclosporine and infliximab. Despite a comparably rapid onset of action, use of systemic steroids should be avoided given high risk of rebound after withdrawal.

Although the most recent expert consensus only recommends acitretin and methotrexate as first-line therapies for stable cases, review of the literature suggests that ustekinumab may also be used in this role.

Evidence supporting the efficacy of ustekinumab comes from 40 documented instances of EP in which the biologic was used as a monotherapy.

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Skip to search form Skip to main content You are currently offline. Some features of the site may not work correctly. DOI: HIV infection can be manifested with different skin symptoms, which are sometimes considered infection markers. Erythrodermic psoriasis is a possible manifestation, which is a widespread form of psoriasis.

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Erythrodermic psoriasis: pathophysiology and current treatment perspectives

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