• Users Online: 1364
  • Print this page
  • Email this page

  Table of Contents  
Year : 2015  |  Volume : 6  |  Issue : 3  |  Page : 207-209  

Ineffectiveness of tumor necrosis factor-α blockers and ustekinumab in a case of type IV pityriasis rubra pilaris

1 Department of Internal Medicine and Medical Specialities, Dermatology Unit, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy
2 Department of Internal Medicine and Medical Specialities, Pathology Unit, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy

Date of Web Publication6-May-2015

Correspondence Address:
Dr. Vito Di Lernia
Dermatology Unit, Arcispedale Santa Maria Nuova-IRCCS, Viale Risorgimento 68, 42123 Reggio Emilia
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2229-5178.156410

Rights and Permissions

Treatment of pityriasis rubra pilaris (PRP) may be difficult since no standardized therapeutic approach has been established. Recently, tumor necrosis factor-α (TNF-α) blockers have been demonstrated to be favorable in the management of recalcitrant PRP. The authors report a case of a patient who presented a type IV PRP or circumscribed, juvenile type. Such a condition follows an unpredictable course, presenting with diffuse, palmoplantar keratoderma and sharply-demarcated areas of follicular hyperkeratosis on the elbows and knees. Treatment with all available TNF-α inhibitors and ustekinumab did not prove to be helpful. The authors suggest that circumscribed variants of PRP could respond to therapy in ways different from classical PRP.

Keywords: Pityriasis rubra pilaris, treatment, tumour necrosis factor, ustekinumab

How to cite this article:
Lernia VD, Ficarelli E, Zanelli M. Ineffectiveness of tumor necrosis factor-α blockers and ustekinumab in a case of type IV pityriasis rubra pilaris. Indian Dermatol Online J 2015;6:207-9

How to cite this URL:
Lernia VD, Ficarelli E, Zanelli M. Ineffectiveness of tumor necrosis factor-α blockers and ustekinumab in a case of type IV pityriasis rubra pilaris. Indian Dermatol Online J [serial online] 2015 [cited 2020 Apr 2];6:207-9. Available from: http://www.idoj.in/text.asp?2015/6/3/207/156410

   Introduction Top

Pityriasis rubra pilaris (PRP) includes a spectrum of rare chronic, idiopathic inflammatory disorders with papulosquamous eruptions of unknown cause. [1] Treatment is challenging. PRP shows consistent clinical heterogeneity; consequently, it is hard to predict the outcome of treatment. Response to therapy may vary with subtype.

   Case Report Top

A 29-year-old female presented for evaluation of a skin condition previously diagnosed as psoriasis vulgaris. There was no family history of psoriasis, palmoplantar keratoderma or other skin diseases. The lesions first appeared at age six years with no preceding trauma or infection and were characterized by palmoplantar keratoderma and demarcated, hyperkeratotic plaques on the elbows and knees. Her symptoms had a spontaneous remission between 13 and 26 years. The patient had been on many systemic treatments over the last two years without response, including cyclosporine (3 mg/kg/day for 3 months), methotrexate (15 mg/weekly for 4 months), adalimumab (two subcutaneous injection of 40 mg at day 0, a subcutaneous injection of 40 mg at day 7 and every 14 days thereafter for 16 weeks), etanercept (50 mg weekly subcutaneous injections for 12 weeks), infliximab (5 mg/kg given as an intravenous infusion at weeks 0, 2, 8).

Physical examination showed a diffuse, orange-pink palmoplantar keratoderma [Figure 1]. Well-defined keratotic follicular papules also involved the dorsal aspects of the hands and feet, elbows and knees [Figure 2] and [Figure 3]. The remainder of her medical history was not significant. A skin biopsy revealed alternating parakeratosis and orthokeratosis, pronounced irregular acanthosis, focal hypergranulosis and mild focal spongiosis. A perivascular lymphocytic infiltration was present in the papillary dermis [Figure 4]. Based on clinical and histologic findings, the patient was diagnosed having PRP, type IV (circumscribed juvenile). PUVA therapy was started 3 times for a week. After 16 weeks the treatment was stopped due to lack of efficacy. Application of keratolytic agents and even bland emollients did not give significant results. Given the childbearing age of the patient acitretin was contraindicated. After voluntary, informed consent, ustekinumab 45 mg subcutaneously at weeks 0 and 4, and quarterly thereafter (patient's weight = 55 kg) was then started, the same posology as in psoriasis. No result was achieved after the third injection. The treatment was stopped, with no adverse events reported. The clinical picture is unchanged.
Figure 1: Keratoderma of the hands with a sharp demarcation of the borders

Click here to view
Figure 2: Diffuse transgrediens palmoplantar keratoderma on the dorsum of hands

Click here to view
Figure 3: Follicular hyperkeratosis and erythema on the elbows

Click here to view
Figure 4: Alternating parakeratosis and orthokeratosis, irregular acanthosis, focal hypergranulosis and a perivascular lymphocytic infiltration in the papillary dermis (H and E ×10)

Click here to view

   Discussion Top

Pityriasis rubra pilaris occurs equally in male and female patients, with a bimodal age distribution, peaking during the first and then the sixth decade. [1] Griffiths proposed a classification for PRP in five subtypes, based upon age, duration, and type of cutaneous involvement. [2] Type I, or classic PRP, is the commonest type (50% of cases) and occurs in adults. It spreads caudally. The patient is usually erythrodermic with diffuse thickening of the palms and soles and possibly ectropion. 80% of patients experience clinical resolution within 3 years. On the basis of Griffith's classification our patient presented the circumscribed, juvenile, or type IV PRP. Clinical manifestations occurred in her prepubertal age and relapsed at age 27, after a long-lasting remission. Type IV PRP develops in prepubertal children presenting with sharply-demarcated areas of follicular hyperkeratosis and erythema on the elbows and knees. A waxy, orange-red, diffuse, palmoplantar keratoderma is also commonly observed. [3] It has an unpredictable course. [4]

Treatment of PRP can be difficult. A standard therapeutic approach does not exist as cases are few and treatment is protracted. In addition, spontaneous remissions are possible. Retinoids and methotrexate are the most frequently used medications with variable effectiveness. [1] Cyclosporine and azathioprine are considered to be alternative therapies. [1],[5] An increasing number of reports document the effectiveness of tumor necrosis factor-α (TNF-α) blockers in recalcitrant PRP. [6] Further, some case reports have documented favorable response of PRP to ustekinumab, a fully human monoclonal antibody which binds to interleukin-12 (IL-12) and IL-23 with high specificity and affinity. [7] An upregulation of TNF mRNA in lesional compared with nonlesional skin in two patients with type I PRP has been demonstrated. [8] A recent retrospective revision investigating treatment options showed a marked clinical in more than 50% of patients with type I PRP treated with TNF antagonists. [9] However, a systematic review of reports of PRP responding positively to TNF-α blockers does not recommend them due to possible reporting bias and spontaneous remissions. [10]

In the literature, the patients who achieved remission with TNF-α blockers or ustekinumab were all consistent with classical type 1 PRP. Our patient who presented a type IV PRP was unresponsive to the TNF-blockers adalimumab, etanercept and infliximab. Ustekinumab was not a helpful therapeutic approach as well. Our clinical experience suggests that in patients with type IV PRP, TNF and IL-12/IL-23 blockade may not be useful targets. Since we observed a primary lack of response to all available TNF-blockers, we suggest that yet unmapped signaling pathways may be involved in type IV PRP.

   Conclusion Top

There seems to be inadequate response of circumscribed variants of PRP to standard therapies that are effective in classical PRP.

   References Top

Klein A, Landthaler M, Karrer S. Pityriasis rubra pilaris: A review of diagnosis and treatment. Am J Clin Dermatol 2010;11:157-70.  Back to cited text no. 1
Griffiths WA. Pityriasis rubra pilaris. Clin Exp Dermatol 1980;5:105-12.  Back to cited text no. 2
Bragg J, Witkiewicz A, Orlow SJ, Schaffer JV. Pityriasis rubra pilaris, type IV. Dermatol Online J 2005;11:14.  Back to cited text no. 3
Albert MR, Mackool BT. Pityriasis rubra pilaris. Int J Dermatol 1999;38:1-11.  Back to cited text no. 4
Cohen PR, Prystowsky JH. Pityriasis rubra pilaris: A review of diagnosis and treatment. J Am Acad Dermatol 1989;20:801-7.  Back to cited text no. 5
Gemmeke A, Schönlebe J, Koch A, Wollina U. Pityriasis rubra pilaris - A retrospective single center analysis over eight years. J Dtsch Dermatol Ges 2010;8:439-44.  Back to cited text no. 6
Ruiz Villaverde R, Sánchez Cano D. Successful treatment of type 1 pityriasis rubra pilaris with ustekinumab therapy. Eur J Dermatol 2010;20:630-1.  Back to cited text no. 7
Zhang YH, Zhou Y, Ball N, Su MW, Xu JH, Zheng ZZ. Type I pityriasis rubra pilaris: Upregulation of tumor necrosis factor alpha and response to adalimumab therapy. J Cutan Med Surg 2010;14:185-8.  Back to cited text no. 8
Eastham AB, Femia AN, Qureshi A, Vleugels RA. Treatment options for pityriasis rubra pilaris including biologic agents: A retrospective analysis from an academic medical center. JAMA Dermatol 2014;150:92-4.  Back to cited text no. 9
Petrof G, Almaani N, Archer CB, Griffiths WA, Smith CH. 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:e131-5.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

This article has been cited by
1 Biologics for pityriasis rubra pilaris treatment: A review of the literature
Monica Napolitano,Damiano Abeni,Biagio Didona
Journal of the American Academy of Dermatology. 2018;
[Pubmed] | [DOI]
2 Pityriasis rubra pilaris: algorithms for diagnosis and treatment
S. Roenneberg,T. Biedermann
Journal of the European Academy of Dermatology and Venereology. 2018;
[Pubmed] | [DOI]
3 A Review on Pityriasis Rubra Pilaris
Dingyuan Wang,Vanessa Cui-Lian Chong,Wei-Sheng Chong,Hazel H. Oon
American Journal of Clinical Dermatology. 2018;
[Pubmed] | [DOI]
4 Off-Label uses of Biologic Agents Approved for Psoriasis and Psoriatic Arthritis for Dermatological Conditions: Part II
Amira Elbendary,Roselyn Kellen
Journal of Psoriasis and Psoriatic Arthritis. 2017; 2(2): 65
[Pubmed] | [DOI]
5 Ustekinumab treatment of pityriasis rubra pilaris: A report of five cases
Monica Napolitano,Luigi Lembo,Luca Fania,Damiano Abeni,Dario Didona,Biagio Didona
The Journal of Dermatology. 2017;
[Pubmed] | [DOI]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
   Case Report
    Article Figures

 Article Access Statistics
    PDF Downloaded236    
    Comments [Add]    
    Cited by others 5    

Recommend this journal