BASICS
DESCRIPTION
- Pityriasis rubra pilaris (PRP) is a rare papulosquamous skin condition characterized by red-orange scaly plaques, palmoplantar keratoderma, and follicular keratotic papules. In adults, lesions typically begin on the scalp, spreading to other areas of the body in a craniocaudal direction, and leaving characteristic islands of spared normal skin ( "nappes claires " �). PRP may progress to generalized erythroderma.
- Divided into subtypes by Griffith classification (1): See "Physical Exam " � section for descriptions.
- Type I: classic adult
- Type II: atypical adult
- Type III: classic juvenile
- Type IV: circumscribed juvenile
- Type V: atypical juvenile
- Type VI: HIV-associated PRP
- In classic adult PRP, >80% of patients experience spontaneous resolution within 3 years. However, atypical adult and juvenile forms are chronic and intractable (2)[C].
- Pediatric considerations: Lesions typically begin on the lower half of the body as opposed to adult presentations and may resemble seborrheic dermatitis. The 3-year remission rate is 32% (2)[C].
EPIDEMIOLOGY
Predominant age: bimodal distribution, most cases occur in the 1st and 5th to 6th decades of life (2)[C]. � �
Incidence
- 1/3,500 to 5,000 patients presenting to dermatology clinics
- No gender predominance
ETIOLOGY AND PATHOPHYSIOLOGY
- Unknown
- Hypothesis that type III may be related to an abnormal immune response to an antigenic trigger.
- Tumor necrosis factor (TNF) mRNA is elevated in PRP lesions similar to the level found in psoriasis, explaining the recent rise and potential value of anti-TNF agents in therapy (3).
- Case reports also document this rash in postinfection states including after streptococcal infections.
- Some studies showed that abnormal vitamin A metabolism and/or vitamin A deficiency may play some role in PRP etiology. However, others did not find any decreased level.
Genetics
Familial occurrence has been described. � �
- Familial type is most often autosomal dominant, but recessive forms have also been described.
- Familial type associated with CARD14 mutation
GENERAL PREVENTION
No known preventive measures � �
COMMONLY ASSOCIATED CONDITIONS
- Erythroderma
- Seronegative arthritis
- Myositis
- Myasthenia gravis
- Hypothyroidism
- Celiac sprue
- Infections, including HIV
- Autoimmune diseases
- Malignancies
DIAGNOSIS
HISTORY
- Adult onset initially presents as a red scaling papule or plaque on the face or upper body.
- Plaques enlarge over days or several weeks spreading in a craniocaudal direction.
- Patients may develop painful palmoplantar fissures.
- Some patients experience pruritus; others may have oral involvement with pain and irritation of the tongue.
PHYSICAL EXAM
- Physical exam varies slightly, depending on which Griffith classification of PRP is present. The following describes the classic adult type, which makes up 55% of all cases (type I):
- Follicular keratotic papules begin on the upper body and coalesce on many areas of trunk to produce sharply bordered, large, scaly, red plaques with islands of normal skin.
- Face assumes a red-orange hue. Palmoplantar keratosis and possibly nail involvement develop in weeks or months.
- Nail involvement, if any, can show distal yellow-brown discoloration, subungual hyperkeratosis, nail thickening, and splinter hemorrhages.
- Palms and soles may acquire the appearance of a "hyperkeratotic sandal, " � with painful fissures, whereas the scalp reveals diffuse scaling.
- Affected skin is extremely rough to touch.
- As the disease progresses, severe erythroderma and ectropion may develop.
- Eruption lasts for months and years; 80% are clear in 3 years.
- Type II (atypical adult): 5% of all cases
- Lesions demonstrate an ichthyosiform pattern; patient also may have alopecia.
- Duration is usually ≥20 years.
- Type III (classic juvenile): 10% of all cases
- Is very similar to type I but onset is within 2 years of life and lasts an average of 1 year
- Type IV (circumscribed juvenile): 25% of all cases
- Localized and occurs in prepubertal children; located on knees, elbows, palms, and soles
- Rarely progresses to widespread classical form
- Type V (atypical juvenile): 5% of all cases
- Majority of familial PRP cases are in this group.
- Occurs in 1st years of life and follows a chronic course
- Mostly hyperkeratotic follicular lesions
- Type VI (HIV-associated): Cases are increasing.
- Lesions are nodulocystic and pustular acneiform.
- Resistant to standard treatments but may respond to antiretroviral therapies
- Dermoscopy may be used to help distinguish between PRP and the main differential diagnosis of psoriasis. Under a dermatoscope, PRP will have yellow/orange plaques (pityriasis) with surrounding linear erythematous vessels (rubra) and a central hair (pilaris); whereas psoriasis will have a white/silvery scale with dotted vessels.
DIFFERENTIAL DIAGNOSIS
- Psoriasis
- Seborrheic dermatitis
- Atopic dermatitis
- Cutaneous T-cell lymphoma
- Erythroderma progressive symmetrica
- Erythrokeratoderma variabilis
- Follicular eczema
- Follicular ichthyosis
- Follicular mycosis fungoides
- Drug-induced eruptions
DIAGNOSTIC TESTS & INTERPRETATION
Diagnosis relies on the distinctive clinical picture and correlation with histopathologic findings (2)[C]. � �
Initial Tests (lab, imaging)
No specific lab markers; WBC count is normal. � �
Diagnostic Procedures/Other
Skin biopsy � �
Test Interpretation
Characteristic histopathologic findings on skin biopsy � �
- Increased granular cell layer
- Acantholysis and acanthosis
- Psoriasiform hyperplasia with alternating vertical and horizontal orthokeratosis and parakeratosis (4)[B]
- Dense, keratotic follicular plugging
- Increased vascularity (4)[B]
- Superficial perivascular lymphocytic infiltrate (4)[B]
- Eosinophils in 38% of cases (4)[B]
TREATMENT
- Topical therapies have limited effectiveness and are often used in combination with systemic therapy (4)[B].
- Most patients (65%) require oral or biologics to obtain a clinical response (3)[B].
- Oral retinoids are the mainstay of treatment of adult PRP (2)[C],(4,5)[B].
- No published randomized controlled trials exist due to rarity of these disorders.
GENERAL MEASURES
- Petroleum-based topical emollients may be helpful for painful fissures (2)[C].
- Emollients with 12% lactic acid (Lac-Hydrin 12%) may provide some relief in areas with keratoderma (2)[C].
- Keratolytics can be applied to the feet and occluded with plastic wrap at night to help remove scale.
MEDICATION
First Line
- Topical corticosteroids are usually tried first due to safety and desire to avoid systemic medication but have low efficacy (35%). If they fail, oral retinoids become first-line (4)[B].
- Type IV PRP typically responds to local therapy, with tazarotene having more efficacy than topical steroids in this type (4)[B].
- Isotretinoin: 1 mg/kg/day for up to 6 months (clinical improvement typically seen in 3 to 7 months) or acitretin 25 to 50 mg/day
- Safety and efficacy not established for pediatric population; retinoids may cause premature closure of epiphyses (2)[C].
- Contraindications: Use cautiously in women of childbearing age.
- Teratogenic agent: Do not use in females who are pregnant, who intend to become pregnant during therapy or within 3 years after discontinuation of therapy, or who may not use reliable contraception during this time period. Requires enrollment into iPledge program
- Patient monitoring: monthly urine HCG, CBC, LFTs, triglycerides, and two forms of contraception in women
- Adverse reactions: elevated LFTs, pruritus, hypertriglyceridemia, alopecia
- Alitretinoin at 30 mg/day has been shown to be successful in case reports and a small retrospective case study. Case study authors suggested an alternative for patients not responding to the current retinoid would be to switch to a different type of retinoid or to increase the dose of current retinoid (5)[B].
Second Line
- If the retinoids fail to exert an effect, methotrexate or TNF-α blockers should be considered.
- Methotrexate 5 to 30 mg/week (2)[C]
- Contraindications: pregnancy, women of childbearing potential, chronic liver disease, hypersensitivity
- Cautions: Monitor closely for renal, lung, or liver toxicity. Good oral care is recommended due to mucositis, infection, peptic ulceration, and ulcerative colitis.
- Recent reports have shown notable and rapid effectiveness of anti-TNF agents: infliximab (5 mg/kg at weeks 0, 2, 6, then every 8 weeks), etanercept (50 mg twice a week), and adalimumab (40 mg/week). However, a systematic review of the literature concluded that although they appear to be of value, a firm recommendation cannot yet be made, and additional studies are needed (1)[A].
- Primarily used in recalcitrant cases who failed oral retinoids and methotrexate (3)[B]
- Have also been used as monotherapy in a few cases, with promising results (1)
- Faster clinical response than isotretinoin or acitretin (5.7 weeks vs. 12 to 28 weeks) (3)[B]
- In one study, 88% (8/9) achieved complete clinical response on TNF agents versus only 56% (8/15) on acitretin or methotrexate (3)[B].
- Contraindications: existing hypersensitivity to antibody proteins, severe heart failure, severe infections
- Cautions: lupus, hepatitis B or C, lymphoma, multiple sclerosis, live vaccines, use of additional immunosuppressants
- Monitoring parameters: tuberculosis and hepatitis screening prior to initiating therapy, TB test repeated annually, watch for signs of infections, heart failure, lupus-like syndromes, elevated LFTs, signs of malignancy
ADDITIONAL THERAPIES
- Cases refractory to treatment with topical and systemic medications should prompt consideration of narrowband UVB phototherapy (2)[C].
- Type VI HIV-associated PRP shows response to antiretroviral therapy, but relapses are frequent (2)[C].
- A systematic review of off-label use of azathioprine gave a weak recommendation for use of azathioprine with PRP, if usual treatment options are contraindicated or fail; supported by C-level quality of evidence (6)[A]
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
- Some cases may spontaneously resolve in 1 to 3 years, whereas others have been shown to persist as long as 20 years; individual prognosis cannot be predicted (5)[B].
- Patients who develop erythroderma should be monitored for electrolyte abnormalities, hypoalbuminemia, hypothermia, secondary bacterial infection in the skin, and possible sepsis.
- As this condition can be widespread and last for multiple years, it is important to monitor patients for psychosocial and emotional sequelae. Available online support group: http://www.prp-support.org/wp/
COMPLICATIONS
- Erythroderma: Patients with erythroderma may develop lymphadenopathy, hepatomegaly, splenomegaly, and electrolyte abnormalities due to increased transepidermal water loss.
- Cardiac failure may occur in patients with preexisting heart conditions.
REFERENCES
11 Petrof � �G, Almaani � �N, Archer � �CB, et al. A systematic review of the literature on the treatment of pityriasis rubra pilaris type 1 with TNF-antagonists. J Eur Acad Dermatol Venereol. 2013;27(1):e131 " �e135.22 Klein � �A, Landthaler � �M, Karrer � �S. Pityriasis rubra pilaris: a review of diagnosis and treatment. Am J Clin Dermatol. 2010;11(3):157 " �170.33 Eastham � �AB, Femia � �AN, Qureshi � �A, et al. Treatment options for pityriasis rubra pilaris including biologic agents: a retrospective analysis from an academic medical center. JAMA Dermatol. 2014;150(1):92 " �94.44 Marrouche � �N, Kurban � �M, Kibbi � �AG, et al. Pityriasis rubra pilaris: clinicopathological study of 32 cases from Lebanon. Int J Dermatol. 2014;53(4):434 " �439.55 Amann � �PM, Susic � �M, Gl � �der � �F, et al. Alitretinoin (9-cis retinoic acid) is effective against pityriasis rubra pilaris: a retrospective clinical study. Acta Derm Venereol 2015; 95:329 " �331.66 Schram � �ME, Borgonjen � �RJ, Bik � �CM, et al. Off-label use of azathioprine in dermatology: a systematic review. Arch Dermatol. 2011;147(4):474 " �488.
ADDITIONAL READING
- Gemmeke � �A, Sch � �nlebe � �J, Koch � �A, et al. Pityriasis rubra pilaris " �a retrospective single center analysis over eight years. J Dtsch Dermatol Ges. 2010;8(6):439 " �444.
- Fuchs-Telem � �D, Sarig � �O, van Steensel � �MA, et al. Familial pityriasis rubra pilaris is caused by mutations in CARD14. Am J Hum Genet. 2012;91(1):163 " �170.
- Lallas � �A, Apalla � �Z, Karteridou � �A, et al. Photoletter to the editor: dermoscopy for discriminating between pityriasis rubra pilaris and psoriasis. J Dermatol Case Rep. 2013;7(1):20 " �22.
- Liao � �WC, Mutasim � �DF. Infliximab for the treatment of adult-onset pityriasis rubra pilaris. Arch Dermatol. 2005;141(4):423 " �425.
- L � �pez-G � �mez � �A, Vera-Casa � �no � � � �, G � �mez-Moyano � �E, et al. Dermoscopy of circumscribed juvenile pityriasis rubra pilaris. J Am Acad Dermatol. 2015; 72(1 Suppl): 858 " �859.
- Sehgal � �VN, Srivastava � �G, Dogra � �S. Adult onset pityriasis rubra pilaris. Indian J Dermatol Venereol Leprol. 2008;74(4):311 " �321.
- Selvaag � �E, Haedersdal � �M, Thomsen � �K. Pityriasis rubra pilaris: a retrospective study of 12 patients. J Eur Acad Dermatol Venereol. 2000;14(6):514 " �515.
- Vergilis-Kalner � �IJ, Mann � �DJ, Wasserman � �J, et al. Pityriasis rubra pilaris sensitive to narrow band-ultraviolet B light therapy. J Drugs Dermatol. 2009;8(3):270 " �273.
- White � �KL. Pityriasis rubra pilaris. Dermatol Online J. 2003;9(4):6.
CODES
ICD10
L44.0 Pityriasis rubra pilaris � �
ICD9
696.4 Pityriasis rubra pilaris � �
SNOMED
- Pityriasis rubra pilaris (disorder)
- Classical adult pityriasis rubra pilaris
- Atypical adult pityriasis rubra pilaris
- Classical juvenile pityriasis rubra pilaris
- Atypical juvenile pityriasis rubra pilaris
CLINICAL PEARLS
- PRP is a rare chronic skin condition with an unknown etiology that can have a profound negative impact on patients ' self-image.
- Diagnosis primarily relies on distinctive clinical findings: orange-red skin hue, papulosquamous plaques with islands of spared normal skin, and hyperkeratotic palmoplantar areas. Dermoscopy will help to distinguish PRP from psoriasis. Skin biopsy will confirm the diagnosis and further distinguish PRP from psoriasis.
- Initial therapy involves topical corticosteroids, followed by isotretinoin or acitretin plus concurrent or later low-dose weekly methotrexate.
- Anti-TNF agents have provided resolution to the recalcitrant cases when isotretinoin, acitretin and methotrexate failed, but although they may be of value, further study is needed before they can be firmly recommended (1)[A],(3)[B].