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Pityriasis rubra pilaris: Prognosis and management

Pityriasis rubra pilaris: Prognosis and management
Literature review current through: Jan 2024.
This topic last updated: Dec 21, 2022.

INTRODUCTION — Pityriasis rubra pilaris (PRP) is a rare, inflammatory, cutaneous, papulosquamous disorder that has a variety of clinical presentations. PRP can cause pruritus, pain, inability to perform daily activities, and cosmetic disfigurement and can have a profound, negative impact on quality of life. Although spontaneous resolution is possible, PRP often persists for years.

Data on the treatment of PRP are limited, contributing to uncertainty regarding the best approach to treatment. Biologic agents, oral retinoids, and methotrexate are the mainstays of treatment (algorithm 1).

The prognosis and management of PRP will be reviewed here. The pathogenesis, clinical manifestations, and diagnosis of PRP are discussed separately.

(See "Pityriasis rubra pilaris: Pathogenesis, clinical manifestations, and diagnosis".)

DISEASE OVERVIEW — PRP may be sporadic or inherited, may occur in adults and children, and may exhibit a variety of clinical manifestations. PRP is often divided into six subtypes:

Type I – Classical adult

Type II – Atypical adult

Type III – Classical juvenile

Type IV – Circumscribed

Type V – Atypical juvenile

Type VI – HIV associated

Classical adult PRP is considered the most common clinical subtype. Common features of classical PRP include follicular, hyperkeratotic papules; waxy, yellow palmoplantar keratoderma; and erythroderma with islands of sparing (picture 1A-K). Limited, focal skin involvement with plaques studded with follicular plugs is characteristic of circumscribed PRP (picture 2). Ichthyosis-like changes and other features are present in atypical PRP (picture 3). (See "Pityriasis rubra pilaris: Pathogenesis, clinical manifestations, and diagnosis", section on 'Clinical subtypes' and "Pityriasis rubra pilaris: Pathogenesis, clinical manifestations, and diagnosis", section on 'Clinical features'.)

PROGNOSIS — PRP is not associated with systemic involvement or risk of mortality. However, morbidity and negative impact on quality of life are high. (See "Pityriasis rubra pilaris: Pathogenesis, clinical manifestations, and diagnosis", section on 'Psychosocial impact'.)

PRP often persists for years. Spontaneous resolution can occur, but the time to resolution is unpredictable. Although associations between subtype and prognosis have been proposed (eg, classical PRP suggested to resolve more readily than atypical or circumscribed PRP) [1], these categories do not reliably predict the likelihood of spontaneous resolution or treatment response [2-4].

Spontaneous resolution is not typically abrupt. The natural course of disease for patients who experience spontaneous resolution appears to follow an initial, severe, inflammatory, and erythrodermic phase that persists for months, followed by slow and gradual improvement over the following years. Rapid resolution in less than one year appears to be more likely to occur in children than adults [2,5]. Recurrence of PRP after an initial remission is rare in adults but may be slightly more common in children [6].

Examples of studies of the prognosis of PRP include:

In a survey study that included 45 adult and 5 pediatric patients recruited from two PRP support group websites who had an "unquestionable" diagnosis of PRP, the average duration of persistent symptoms among 32 adults with active disease at the time of enrollment was 67 months (range 2 to 484 months). The average time to symptom resolution for the 13 adults with resolved symptoms was 33 months (range 8 to 72 months) [7].

In a retrospective study of 57 patients (41 adults and 16 children) with PRP evaluated at a single center between 1929 and 1967, complete resolution occurred in 49 percent of patients at a mean of 2.3 years after symptom onset (range three months to seven years) [5].

In various pediatric case series, the proportion of patients achieving near or complete resolution of childhood-onset PRP has been reported as 83 percent (with follow-up ranging from 1 to 20 years) [2], 43 percent (with follow-up period unspecified) [6], and 48 percent (with follow-up ranging from two months to nine years) [8].

TREATMENT PRINCIPLES — Efficacy data for PRP are limited, and spontaneous resolution is possible, contributing to uncertainty about the best approach to treatment. Our approach is reviewed here; other approaches may be reasonable (algorithm 1):

Goals of treatment – Goals of treatment include the improvement of symptoms and achievement of long-term clinical remission of skin lesions.

General approach – The approach to treatment generally consists of the following:

Skin care measures and topical therapies to improve symptoms (see 'Skin care' below)

Systemic treatment for PRP (see 'Initial systemic treatment' below)

Patient support (see 'Patient support' below)

Historically, oral retinoids and oral methotrexate have been regarded as the first-line systemic therapies for PRP. However, targeted biologic therapies are increasingly used for PRP, based upon clinical experience that suggests efficacy and lower risk of serious adverse effects. It is generally accepted that PRP does not respond well to oral glucocorticoids. (See 'Initial systemic treatment' below.)

Assessing response – An excellent response to treatment consists of near or complete resolution of skin lesions and associated symptoms. PRP is relatively slow to respond to systemic therapy. A two- to three-month medication trial is often necessary to assess efficacy prior to switching to an alternative therapy, and if significant improvement is noted by the clinician and patient, therapy should be continued for another two to three months before the full therapeutic response is achieved [9].

Cessation of treatment – Patients who respond well to treatment may be able to discontinue treatment or may require continued therapy to remain in remission. We typically discontinue systemic therapy without a taper for patients who achieve complete remission, since in our experience, many patients will stay in remission off therapy. Systemic therapy can be restarted if signs of disease activity recur.

In contrast, patients who have achieved only partial remission with treatment may be at greater risk for relapse following treatment cessation. In a study of 12 patients with PRP treated with ixekizumab, all four patients who achieved 89 to 100 percent improvement in disease severity at the end of the 24-week treatment period remained in remission at week 36, whereas the three patients with 52 to 84 percent improvement worsened following discontinuation of ixekizumab [10].

SKIN CARE — Topical interventions may help to improve symptoms associated with skin lesions (eg, pain secondary to fissures). Emollients are the mainstay of topical treatment.

Emollients — Emollients improve patient comfort by decreasing exfoliative scale and maintaining the skin barrier. We typically advise patients to apply a bland ointment, such as petrolatum, to all affected areas once to multiple times daily. Patients who dislike ointments may prefer bland, cream-based emollients.

Keratolytic agents — Urea 40% cream is helpful as a keratolytic for the palms and soles, especially for patients with thick keratoderma and fissuring. Hydrocolloid dressings provide comfort for palmoplantar fissures. (See "Pityriasis rubra pilaris: Pathogenesis, clinical manifestations, and diagnosis", section on 'Palmoplantar keratoderma'.)

Topical corticosteroids — Topical corticosteroids are often prescribed but whether topical corticosteroids are more effective than emollients is unclear. In a survey study, 19 of 38 patients (50 percent) treated with topical corticosteroids considered topical corticosteroids helpful compared with 34 of 45 patients (76 percent) treated with emollients [7].

A reasonable approach to topical corticosteroid therapy consists of a two-week trial of a medium-potency (eg, group 4) topical corticosteroid applied daily to affected areas on the trunk or extremities; lower-potency (eg, groups 6 or 7) topical corticosteroids are used for the face and intertriginous skin (table 1). If the patient does not have significant improvement within two weeks, the corticosteroid should be discontinued.

INITIAL SYSTEMIC TREATMENT

Patient selection — Systemic therapy plays an important role in the treatment of most patients with PRP and is typically started promptly for adults with widespread or highly symptomatic PRP. An initial trial of topical therapy alone is an alternative initial approach for patients with limited or circumscribed PRP (algorithm 1).

A more conservative approach is sometimes taken for children with PRP. (See 'Children' below.)

Treatment selection — Injectable biologic inhibitors of the interleukin (IL) 17 or IL-23 pathway are our preferred first-line systemic therapies for adults and children with PRP (algorithm 1). Oral retinoids and methotrexate are alternative initial therapies with a long history of use for PRP.

Data are insufficient for conclusions on the relative efficacy of oral retinoids and methotrexate compared with biologic therapy. Our preference for biologic therapy is based upon the more favorable side effect profile and the limited available data that suggest efficacy of biologic anti-IL-17 and anti-IL-23 therapies. Other clinicians advocate for the initial use of nonbiologic therapies [11,12].

IL-17 inhibitors — The IL-17 inhibitors (ixekizumab, secukinumab, and brodalumab) may be beneficial for PRP. Ixekizumab and secukinumab inhibit IL-17A. Brodalumab blocks the IL-17 receptor A. Expression of IL-17A, a proinflammatory cytokine, appears to be upregulated in skin from patients with PRP [13] (see "Pityriasis rubra pilaris: Pathogenesis, clinical manifestations, and diagnosis", section on 'Pathogenesis'):

Administration – Studies directly comparing the efficacy of individual IL-17 inhibitors for PRP are lacking. We consider ixekizumab, secukinumab, and brodalumab all appropriate choices for initial therapy for adults with PRP.

Our preferred IL-17 inhibitors for children are ixekizumab and secukinumab, based upon pediatric data that support efficacy and safety of these drugs for psoriasis in children. Ixekizumab and secukinumab are US Food and Drug Administration (FDA) approved for the treatment of psoriasis in children age six years and older. (See "Psoriasis in children: Management of chronic plaque psoriasis", section on 'Biologic agents'.)

Treatment regimens for PRP typically mimic the regimens used for psoriasis:

Adults:

-Ixekizumab: 160 mg at week 0; 80 mg at weeks 2, 4, 6, 8, 10, and 12; then 80 mg every four weeks

-Secukinumab: 300 mg once weekly at weeks 0, 1, 2, 3, and 4, then 300 mg every four weeks

-Brodalumab: 210 mg at weeks 0, 1, and 2, then 210 mg once every two weeks

Children:

-Ixekizumab: weight-based dosing; for children <25 kg, 40 mg at week 0, then 20 mg every four weeks; for children 25 to 50 kg, 80 mg at week 0, then 40 mg every four weeks; for children >50 kg, 160 mg at week 0, then 80 mg every four weeks

-Secukinumab: weight-based dosing; for children <50 kg, 75 mg at weeks 0, 1, 2, 3, and 4, then 75 mg every four weeks; for children ≥50 kg, 150 mg at weeks 0, 1, 2, 3, and 4, then 150 mg every four weeks

Efficacy – Efficacy data for IL-17 inhibitors are limited to single-arm studies. In an open-label study in which 12 adults with moderate to severe PRP (including 11 who failed at least one other systemic therapy) were treated with ixekizumab for 24 weeks, seven (58 percent) achieved at least a 50 percent reduction in clinician-assessed severity (as measured by the Psoriasis Area and Severity Index [PASI]) [10]. The mean time to improvement was approximately seven weeks, and the median itch score on a 10-point numeric rating scale (with 10 being the worst itch and 0 being no itch) decreased from 7 to 1 over the treatment period. There were no serious or unexpected adverse events. Furthermore, ixekizumab led to normalization in gene expression of IL-17A and other dysregulated genes in the skin after 24 weeks [14].

Another open-label study assessed outcomes of 24 weeks of secukinumab therapy in 12 patients with adult-onset PRP and at least 10 percent body surface area involvement [15]. All patients had a history of failure to respond to topical corticosteroids and at least one systemic agent. At week 28, rates of 50, 75, or 90 percent improvement in the PASI score among the 11 patients available for outcome assessment were 73, 55, and 27 percent, respectively. In addition, ribonucleic acid (RNA) sequencing performed after two weeks of secukinumab therapy revealed improvement in the gene expression patterns in lesional skin.

In addition, multiple case reports and case series report improvement with IL-17 inhibitor therapy in patients with PRP, including PRP resistant to other therapies and familial PRP. These reports describe benefit from ixekizumab [16-21], secukinumab [22-28], and brodalumab [29-31].

Adverse effects – Side effects of IL-17 inhibitors can include injection site reactions and an increased risk of upper respiratory tract infection, oral candidiasis, conjunctivitis, and tinea infection. There is a rare risk of inflammatory bowel disease. Brodalumab also carries a United States boxed warning for suicidal ideation and behavior. (See "Ixekizumab: Drug information" and "Secukinumab: Drug information" and "Brodalumab: Drug information".)

IL-23 inhibitors — IL-23 inhibitors used for PRP include ustekinumab, which inhibits the p40 subunit of IL-12 and IL-23; guselkumab, risankizumab, and tildrakizumab target the p19 subunit of IL-23. The IL-23/Th17 axis is thought to play an important role in the pathogenesis of PRP [13] (see "Pityriasis rubra pilaris: Pathogenesis, clinical manifestations, and diagnosis", section on 'Pathogenesis'):

Administration – Studies directly comparing the efficacy of individual IL-23 inhibitors for PRP are lacking. We consider ustekinumab, guselkumab, risankizumab, and tildrakizumab all appropriate choices for initial therapy for adults with PRP.

Our preferred IL-23 inhibitor for children is ustekinumab, based upon pediatric data that support efficacy and safety for psoriasis in children. Ustekinumab is FDA approved for the treatment of psoriasis in children six years of age and older. (See "Psoriasis in children: Management of chronic plaque psoriasis", section on 'Biologic agents'.)

Treatment regimens for PRP typically mimic regimens used for psoriasis:

Adults:

-Ustekinumab: Adults ≤100 kg is 45 mg given at weeks 0, 4, and every 12 weeks thereafter. A 90 mg dose given in the same regimen is recommended for adults who weigh more than 100 kg.

-Guselkumab: 100 mg at weeks 0, 4, and then every 8 weeks.

-Risankizumab: 150 mg at week 0 and week 4, then every 12 weeks.

-Tildrakizumab: 100 mg at week 0 and week 4, then every 12 weeks.

Children:

-Ustekinumab: weight-based dosing; for children ≤60 kg, 0.75 mg/kg; for children >60 to ≤100 kg, 45 mg; for children >100 kg, 90 mg; ustekinumab is given at weeks 0, 4, then every 12 weeks

Efficacy – There are multiple reports of benefit of IL-23 inhibitors in PRP. However, data are limited to case reports, and the efficacy rate of these agents for PRP remains unclear. A systematic review of reports of systemic therapy for PRP found documentation suggestive of an excellent response in 10 of 16 patients (63 percent) treated with ustekinumab, with an average time to therapeutic response of six weeks [9]. Another systematic review of reports documenting responses of type 1 PRP to various therapies found documentation consistent with a "very good response" in 12 of 17 patients (71 percent) treated with ustekinumab, with improvement noted within the first four weeks [11].

In addition, a survey study of patient-reported outcomes with IL-23 inhibitors found that 48 of 80 patients (60 percent) who had received ustekinumab or guselkumab described their outcomes as "complete clearance" or "substantial improvement" [32]. Response rates were similar in the subset of pediatric patients, with 8 out of 12 juvenile survey respondents (67 percent) reporting "substantial improvement" with ustekinumab.

Case reports describe successful treatment of refractory PRP with risankizumab [33-35] and tildrakizumab [36].

Adverse effects – Adverse effects of IL-23 inhibition can include hypersensitivity reactions and infections, although the risk of serious adverse events is not significantly different from placebo in meta-analyses of psoriasis trials [37]. (See "Ustekinumab (including biosimilars): Drug information" and "Guselkumab: Drug information" and "Risankizumab: Drug information".)

Alternative initial therapies — Oral retinoids and methotrexate are alternative initial therapies (algorithm 1). The efficacy of oral retinoids and methotrexate has not been compared in randomized trials, contributing to uncertainty regarding relative efficacy.

We typically use the oral retinoid isotretinoin for initial treatment when patients cannot obtain or tolerate biologic therapy [9]. We reserve initial treatment with methotrexate for patients who cannot obtain or tolerate biologic or oral retinoid therapy. In a systematic review of published reports documenting systemic therapy for PRP, excellent responses were reported more frequently with isotretinoin than with methotrexate (61 percent of 167 patients versus 33 percent of 160 patients) [9].

Oral retinoids — Oral retinoids, such as isotretinoin, acitretin, alitretinoin, and etretinate, may be beneficial for PRP. Alitretinoin and etretinate are not available in the United States. We typically treat with isotretinoin. Our preference for isotretinoin over acitretin is based upon clinical experience that suggests greater efficacy of isotretinoin for PRP [9].

Caution is indicated for oral retinoid therapy in individuals of childbearing potential. Oral retinoids are teratogenic, and pregnancy must be avoided during therapy and for specific periods following the cessation of therapy (see "Acitretin: Drug information" and "Isotretinoin: Drug information"):

Administration – The best dosing regimens for oral retinoid therapy for PRP are unclear. We typically treat with isotretinoin, starting at 0.5 mg/kg per day and increase to 1 mg/kg per day after one month provided the patient is tolerating therapy. Acitretin is often given at a dose of 0.5 mg/kg per day. Signs of improvement are expected within two months. (See 'Treatment principles' above.)

Early reports of use in PRP suggested that higher doses may be more effective, but this must be balanced with increased risk for adverse effects. For example, isotretinoin was given at an average dose of 2.13 mg/kg, with maximum doses over 3 mg/kg/day in a case series that reported 43 of 45 patients as "clearly improved" [38].

Efficacy – The relative efficacy of individual oral retinoids is unclear. Alitretinoin and isotretinoin were associated with higher proportions of excellent responses compared with acitretin and etretinate in a systematic review of case reports and retrospective case series [9]. Excellent responses were achieved in 73 percent of patients for alitretinoin, 61 percent for isotretinoin, 47 percent for etretinate, and 25 percent for acitretin.

Another systematic review of reports of therapies for type I PRP found documentation supportive of a "very good response" in 27 of 75 patients (36 percent) treated with acitretin as monotherapy and 19 of 23 patients (83 percent) treated with acitretin plus biologic therapy [11]. In a survey study that included 32 patients with PRP treated with oral retinoids, 19 patients (59 percent) described oral retinoids as "helpful" [7].

Adverse effects – Common side effects of oral retinoids include dry skin, cheilitis, headache, alopecia, and increased serum cholesterol and triglyceride levels. These adverse effects tend to be dose dependent. In a systematic review of reports of systemic therapy for PRP, adverse events occurred in 34 percent of patients treated with oral retinoids, a rate higher than reported for other therapies [9]. Laboratory monitoring for oral retinoids is reviewed separately. (See "Acitretin: Drug information" and "Isotretinoin: Drug information".)

In addition, oral retinoids are teratogenic and must be used with caution in individuals. For acitretin, pregnancy should be avoided during treatment and for the following three years; therefore, use of acitretin in individuals of childbearing potential is generally avoided. Pregnancy should be avoided during and for one month following isotretinoin therapy. In the United States, isotretinoin can only be prescribed through the iPLEDGE risk evaluation and mitigation strategy (REMS) program. (See "Acitretin: Drug information" and "Isotretinoin: Drug information".)

Methotrexate — Low-dose methotrexate may be beneficial for PRP. The antiproliferative and anti-inflammatory effects of methotrexate are proposed to contribute to benefit [12].

Certain comorbidities can inhibit the use of methotrexate in some patients. Caution is indicated for patients with hepatic impairment or renal insufficiency. Methotrexate is contraindicated in pregnancy, and caution is also indicated when treating individuals of childbearing potential. Avoidance of alcohol consumption is recommended during treatment:

AdministrationMethotrexate may be given orally or subcutaneously. Dosing for adults is usually 10 to 25 mg given once weekly.

Most adults can be started at 15 mg once weekly and increased up to 25 mg weekly, as tolerated, after the first month. Dose adjustments are indicated for patients with renal dysfunction. Subcutaneous administration may be beneficial for patients requiring more than 15 mg per week, as this may optimize drug absorption and minimize gastrointestinal side effects. Clinical improvement is expected within three months [9]. (See "Use of methotrexate in the treatment of rheumatoid arthritis", section on 'Absorption and route of administration'.)

Folic acid should be administered during methotrexate therapy to reduce risk for adverse effects. A typical dose of folic acid is 1 mg per day. Laboratory monitoring for adverse effects of methotrexate is also indicated. (See "Use of methotrexate in the treatment of rheumatoid arthritis", section on 'Folic acid supplementation'.)

Efficacy – Support for the use of methotrexate stems from case reports and case series. A systematic review of the literature published from 1964 to 2017 that identified a total of 116 patients treated with methotrexate alone or in combination with other systemic therapies found documentation consistent with total clearance or excellent improvement in 23 and 17 percent of patients, respectively [12]. Other systematic reviews of reports of methotrexate for PRP have identified documentation of either "excellent" or "very good" responses in approximately one-third of the reported patients [9,11].

Adverse effects – Common side effects of low-dose methotrexate include headache; nausea; and mild, transient elevations in liver transaminases. Uncommon, serious adverse reactions include bone marrow suppression, severe liver injury, interstitial pneumonitis, and hepatotoxicity. Methotrexate is contraindicated in pregnancy. Laboratory monitoring for methotrexate is reviewed separately. (See "Methotrexate: Drug information".)

REFRACTORY DISEASE — Data are insufficient for conclusions on the best course following treatment failure. Responses to biologic therapies following failure of retinoids, methotrexate, or other biologic therapies have been reported [10,32]. (See 'Treatment principles' above.)

Our general approach to failure of initial treatment is as follows (algorithm 1):

Insufficient response to biologic IL-17 or IL-23 inhibitor – Switch to different class of biologic drug (eg, switch from anti-interleukin [IL] 17 drug to anti-IL-23 drug or vice versa) or add oral retinoid or methotrexate to biologic therapy

Insufficient response to oral retinoid or methotrexate – Switch to anti-IL-17 or anti-IL-23 biologic drug

Additional options for the treatment of PRP include biologic tumor necrosis factor (TNF)-alpha inhibitors, phototherapy, and other therapies. (See 'Other therapies' below.)

SPECIAL POPULATIONS

Children — Topical therapy is generally preferred for the management of circumscribed PRP in children. However, functionally limiting disease (eg, significant involvement of the palms and soles) may prompt use of systemic treatment. (See 'Skin care' above and 'Initial systemic treatment' above.)

Similar to adults, children with extensive skin involvement, such as that occurs in classical PRP, are candidates for systemic therapy. As spontaneous improvement may be more likely in children than adults, the degree to which symptoms impact the child's quality of life plays a role in the decision to initiate systemic treatment. (See 'Prognosis' above and 'Initial systemic treatment' above.)

HIV-associated pityriasis rubra pilaris — Treatment of HIV-associated PRP can be challenging, and data on treatment efficacy are limited. Improvement in HIV-associated PRP with triple antiretroviral therapy (zidovudine [AZT], lamivudine, and saquinavir) was documented in a case report [39]. Other reports document variable responses to AZT, oral retinoids, and phototherapy [40].

Successful treatment in the absence of antiretroviral therapy has not been reported. A reasonable initial approach is antiretroviral therapy for HIV infection, with the addition of systemic therapy for PRP if improvement does not occur. Oral retinoids are generally used because of a lack of immunosuppressive effects. Cautious use of systemic immunomodulatory therapies for PRP may be an additional option for patients with severe, symptomatic PRP.

CARD14-associated papulosquamous eruption — CARD14-associated papulosquamous eruption (CAPE) is an entity first described in 2018 and defined by the presence of psoriasis-like and/or PRP-like skin manifestations in patients with CARD14 gene mutations. A case series and case report suggest benefit of ustekinumab [41,42]. In a study of 15 kindreds with CAPE, five of six patients achieved a near complete response, and one patient had a partial response to ustekinumab therapy [41].

Responses to conventional topical and systemic therapies used for psoriasis were minimal in the study of 15 kindreds. In contrast, acitretin therapy was associated with near complete clearance of skin lesions in a young child with CAPE [43].

OTHER THERAPIES — Additional therapies that may have efficacy for PRP include tumor necrosis factor (TNF)-alpha inhibitors, phototherapy, and other therapies.

TNF-alpha inhibitors — Biologic tumor necrosis factor (TNF)-alpha inhibitors, such as infliximab, adalimumab, and etanercept, have been reported as beneficial for PRP. Although TNF-alpha inhibitors were the first biologic agents used in the treatment of PRP, recognition of an important role for the interleukin (IL) 23/IL-17 axis in PRP has contributed to increased use of biologic IL-17 and IL-23 inhibitors for PRP. (See "Pityriasis rubra pilaris: Pathogenesis, clinical manifestations, and diagnosis", section on 'Pathogenesis' and 'IL-17 inhibitors' above and 'IL-23 inhibitors' above.)

As with other therapies, data on efficacy are derived from case reports and case series [9,11,44]. One systematic review of published reports of systemic therapy for PRP identified documentation consistent with an excellent response in 28 of 49 patients (57 percent) given infliximab, 16 of 30 patients (53 percent) given etanercept, and 13 of 28 patients (46 percent) given adalimumab [9]. In a survey study that included 132 patients treated with TNF-alpha inhibitors, 10 and 35 percent of patients reported complete clearance and substantial improvement, respectively [32].

Phototherapy — Phototherapy in the form of psoralens with ultraviolet A (PUVA) or narrowband ultraviolet B (NBUVB) is more often reported to be ineffective or cause exacerbation of PRP, although there are occasional case reports of treatment success, especially in combination with acitretin [11]. In a retrospective survey, only 1 of 13 patients with PRP found phototherapy helpful [7]. We do not typically use phototherapy for PRP.

It has been proposed that the type of phototherapy may be relevant. In a case report, a patient, in whom phototesting revealed exacerbation of skin disease following ultraviolet B (UVB) but not ultraviolet A (UVA), achieved sustained remission following treatment with bath PUVA [45,46]. (See "Psoralen plus ultraviolet A (PUVA) photochemotherapy" and "UVB phototherapy (broadband and narrowband)".)

Other therapies — Examples of other therapies for which benefit for PRP has been reported in case reports or case series but are less frequently used for this indication include cyclosporine, mycophenolate mofetil, azathioprine, fumaric acid esters, intravenous immune globulin, and apremilast [9,11]. An advantage of cyclosporine is the rapid onset of action (often within one month). However, cyclosporine is associated with risk for serious adverse effects, and a systematic review of published reports of systemic therapy for PRP found documentation of an "excellent" response in only 12 percent of patients treated with cyclosporine [9].

PATIENT SUPPORT — PRP can have a profound, negative psychologic impact, which should be supported and treated alongside the skin manifestations:

Support from other patients – Referral to support groups, such as the PRP Alliance or RareConnect, may be beneficial.

Support for mental health – Disease-related depression appears to be common in PRP, and even suicidality may not be uncommon among patients with moderate to severe PRP [7,47]. Patients experiencing such symptoms should be assessed and referred to a mental health professional. (See "Pityriasis rubra pilaris: Pathogenesis, clinical manifestations, and diagnosis", section on 'Psychosocial impact'.)

SUMMARY AND RECOMMENDATIONS

Prognosis – Pityriasis rubra pilaris (PRP) is a rare, cutaneous, papulosquamous disorder that can negatively affect quality of life. The prognosis of PRP is variable and unpredictable; PRP may spontaneously resolve within a few years or exhibit a prolonged course. (See 'Disease overview' above and 'Prognosis' above.)

Treatment principles – The major treatment goals for PRP are improvement of symptoms and the achievement of long-term remission. Typical components of treatment include skin care with topical therapies to improve patient comfort (eg, emollients and keratolytics), systemic treatment, and patient support (algorithm 1). (See 'Treatment principles' above and 'Skin care' above.)

Systemic therapy is appropriate for patients with widespread or highly symptomatic PRP. The response to systemic treatment tends to be delayed, often requiring at least two to three months of treatment prior to assessing for response. (See 'Treatment principles' above and 'Initial systemic treatment' above.)

Initial systemic therapy – Biologic interleukin (IL) 17 inhibitors, biologic IL-23 inhibitors, oral retinoids, and methotrexate are the mainstays of initial systemic treatment (algorithm 1). (See 'Treatment selection' above.)

For patients who require systemic therapy, we suggest a biologic IL-17 or IL-23 inhibitor as initial therapy, rather than oral retinoid or methotrexate (Grade 2C). This preference is based upon the more favorable side effect profile of these biologic therapies. (See 'IL-17 inhibitors' above and 'IL-23 inhibitors' above.)

For patients who cannot obtain or tolerate biologic therapy, we suggest oral isotretinoin rather than methotrexate for initial treatment (Grade 2C). Efficacy of these drugs has not been directly compared. However, review of data from case reports and case series suggest isotretinoin may be more likely to be effective for PRP. (See 'Alternative initial therapies' above.)

For patients who cannot obtain or tolerate a biologic agent or oral retinoids, methotrexate is appropriate for initial treatment. (See 'Alternative initial therapies' above.)

Patient support – PRP can have a profound, negative impact on quality of life. Some patients may find patient support groups or referral to a mental health professional helpful. (See 'Patient support' above.)

Cessation of treatment – Continuation of treatment is not always necessary to maintain remission. Treatment can be discontinued for patients who achieve clinical remission. Treatment can be restarted if signs of disease activity recur. (See 'Treatment principles' above.)

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Topic 131425 Version 4.0

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