1.5.3 Pityriasis rubra pilaris (Prp)

Susceptibility to PRP. No clear genetic background exists, however, the fact that type 5 occurs after birth suggests a genetic predisposition. The genetic basis for familial cases, most commonly categorized under the fifth subtype. It has been mapped to gain of function mutations in the caspase recruitment domain family, member 14 (CARD14) gene (chromosome 17q25.3). The IL-23/TH17 pathway proteins, IL-17C and CCL20 is upregulated in tissue. Furthermore, the levels seemed to correlate with PRP disease severity and responsiveness to cytokine IL-17A blockade treatment. It is occasionally precipitated and aggravated or even maintained by infections or drugs such as sorafenib, insulin, imatinib, telaprevir, and vaccinations.

Lesions may cover the entire body including erythrodermic courses or may be localized such as at the elbows and knees, palms and soles. Often there are areas of uninvolved skin, particularly on the trunk and limbs, which are referred to as nappes claires. The palms and soles are usually involved and become diffusely thickened and yellowish and mimic psoriasis, chronic palmo-plantar eczema or keratodermas. The atypical adult type 5 may also show ichthyosis-like lesions, the circumscribed juvenile type shows involvement of knees and elbows exclusively.

In the microscopic specimen one sees vertical and horizontal alternating areas with ortho- and parakeratosis (checker board pattern), waving hypergranulosis, thickened suprapapillary plates, broadened rete ridges and a circumscribed non-prominent, superficial perivascular infiltrate. A diagnostic clue is that of follicular hyperkeratotic plugs.

Average disease course in about 57 % of patients was one year or less.

• Type 1 accounts for 50% of all cases and has a good prognosis with the majority of cases going into spontaneous remission within 2- 3 years. There is some evidence of association with underlying malignacy.

• Type 2 accounts for about 5% of all cases and shows long persistence of up to 20 years.

• Type 3 accounts for about 10% of all cases and shows early onset between 5 and 10 years old. It can follow acute streptoccocal or viral infections and often shows remission in the first year.

• Type 4 accounts for about 25% of all cases and occurs in prepubertal children with a specific pattern confined to palms, soles, knees and elbows. No clear time of course.

• Type 5 accounts for about 5% of all cases. Inheritance is discussed. Occurs already at birth or early in childhood and shows long-term persistence. CARD14 variants are seen as a predisposing factor to autoinflammatory keratinization in juvenile PRP.

• Type 6 is very rare. No predictable course and refractory to common treatments. May improve with HIV treatment.

None except erythrodermic courses and type 1 and VI associated with an underlying malignancy disorder or HIV infection.

• In particular, juvenile and adult psoriasis and other types of erythroderma. Pityriasiform or guttate like lesions such as in secondary syphilis, pityriasis rosea, in those of the parapsoriasis group, and in cutaneous T-cell lymphoma.

• Chronic nummular eczema, hypertrophic lichen planus, chronic palmo-plantar eczema

• Phrynoderma, Keratosis follicularis, Darier’s disease

Prevention

Avoidance of aggravating factors.

Therapy

In general, depending on the PRP subtype. Topical therapy is not evidence-based by supporting trial data.

Topical therapy:

• Topical therapy is indicated depending on lesion type and amount of body surface area as well as age.

• Topical corticosteroids, especially mid to higher potency.

• Vitamin D3 and its analogues (calcipotriol, tacalcitol).

• Combination of betamethasone and calcipotriol.

• Vitamin-A acid derivatives (tazarotene gel).

• UV light therapy regimen such as photo bath therapy 15% NaCl + UVB.

• Phototherapy (UVA +) UVB/narrow band UVB 311 nm.

• Photochemotherapy: 8-(5-) MOP + UVA (PUVA) via local cream, via full skin

Systemic treatment:

To qualify for systemic therapy the PRP must be widespread. No evidenced based data are existing to support any of the following therapeutics, therefore off-label indications are common. If topical therapy fails to control symptoms consider:

1. Methotrexate oral or subcutaneous.

2. Azathioprine

3. Retinoids, i.e. acitretin, isotretinoin, alitretinoin

4. Ciclosporin

5. Fumarates

6. Biologics such as TNF alpha inhibitors, ustekinumab, secukinumab, tildrakizumab