Scaly erythematous rash

CASE #1Pityriasis rubra pilaris (PRP) is a rare and chronic papulosquamous dermatosis. Classically characterized by red-orange scaly plaques, hyperkeratotic follicular papules, and palmoplantar hyperkeratosis, PRP is an inflammatory disorder of unknown etiology.Although there is great clinical heterogeneity and patients present...

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CASE #1

Pityriasis rubra pilaris (PRP) is a rare and chronic papulosquamous dermatosis. Classically characterized by red-orange scaly plaques, hyperkeratotic follicular papules, and palmoplantar hyperkeratosis, PRP is an inflammatory disorder of unknown etiology.

Although there is great clinical heterogeneity and patients present with varying degrees of the characteristic lesions mentioned, well-demarcated islands of spared skin are common and erythroderma is an oft-reported complication.

The Griffiths classification system divides PRP into 5 categories: classic adult type, atypical adult type, classic juvenile type, circumscribed juvenile type, and atypical juvenile type.^1,2 The classic adult type is the most common form, presenting with the characteristic features mentioned, and has the best prognosis. 

A new form of the disease associated with human immunodeficiency virus (HIV) has been recently described and classified as type VI. In addition, recent reports have associated PRP with malignancy.³


The etiology of PRP is unknown, and most cases are sporadic. It has been suggested that tumor necrosis factor alpha (TNF-α) may play a pathogenic role, given the evidence of increased expression in some patients and the effect of TNF-α inhibitors in treatment.⁴ 

A familial form with an autosomal-dominant pattern of inheritance has been noted and recently associated with mutations in the CARD14 gene.^5,6 There have also been case reports of PRP occurring after streptococcal infections, perhaps as an autoimmune response to an antigenic trigger.⁷ Lastly, abnormalities in vitamin A metabolism have been associated with the development of PRP, but its role is still unclear.


PRP usually presents early in childhood in the familial form and at any time in the sporadic form, although there are peaks of occurrence in the first decade of life and between ages 40 and 60 years. PRP typically progresses from the face and scalp to the palms and soles, eventually covering the entire body over the course of a few weeks to a few months and affecting the skin, nails, mucous membranes, and eyes. 

Physical findings of the skin include red-orange scaly plaques with sharply demarcated borders and areas of spared skin, also known as “islands of sparing.” Palms and soles are thickened, waxy, and may have an orange hue. The elbows and dorsal surface of the proximal phalanges develop follicular hyperkeratosis, also known as “nutmeg grater papules.” 

The nails can become discolored, thickened with subungual hyperkeratosis, and may show splinter hemorrhages. Some patients present with changes in the buccal mucosa, such as a whitish discoloration or white and gray plaques and papules, resulting in pain and irritation.⁸ 

Patients with chronic disease commonly develop ectropion or erythroderma, which is associated with increased morbidity. 


The treatment of PRP is difficult, and no controlled trials have been done. Therapy is largely based on anecdotal reports and management mainly involves both systemic and topical therapy.⁹ The most commonly used treatments, especially for patients with severe, extensive PRP, are systemic oral retinoids and immunosuppressants such as methotrexate, cyclosporine, and azathioprine.¹⁰ 

In some cases, biological TNF-α inhibitors have been successful.¹¹ Topical medications such as corticosteroids and retinoids are used more often in patients with limited disease because these agents provide some relief of symptoms but don’t have a long-term effect. 

In persons with PRP refractory to treatment with topical or systemic medications, phototherapy and extracorporeal photochemotherapy have been shown to be successful.¹² Some evidence suggests that narrowband ultraviolet B (UVB) phototherapy may be more effective than broadband UVB.¹³

Prognosis is dependent on the form of PRP. Prospects are best for the type I form and in acquired sporadic cases, both of which present with acute onset and resolve spontaneously within 1 to 3 years in 80% of patients.¹⁴ 


The differential diagnosis of PRP includes plaque psoriasis, erythrokeratodermia variabilis, and cutaneous T-cell lymphoma. Diagnosis is confirmed based on clinical findings and histologic findings and can serve to differentiate between PRP and plaque psoriasis. 

Characteristic findings on light microscopy in adult classical PRP are distinct, although they may vary based on the stage of the disease process. A checkerboard or basket-weave pattern of hyperkeratosis with alternating orthokeratosis and parakeratosis can be seen. 

Follicular plugging is prominent and accompanied by parakeratosis in the perifollicular shoulder.¹⁵ Broad rete ridges with narrow dermal papillae, a mild perivascular infiltration of lymphocytes in the superficial dermis, hypergranulosis, and acantholysis can be seen as well.¹⁶


PRP may be confused with plaque psoriasis, given that both disorders present with erythematous, scaly plaques and can have a similar distribution. Regarding age of onset, PRP has a bimodal distribution whereas psoriasis is more common in the second decade of life. 

A cardinal difference between the two is that lesions in PRP are characterized by reddish-orange plaques and palmoplantar keratoderma with an orange hue whereas in psoriasis, the plaques are more silvery and scaly and adherent to an erythematous base. 

There are also characteristic differences in histology between PRP and psoriasis, which help differentiate the two. In PRP, unlike in psoriasis, the acanthotic epidermis is not thinned above the dermal papillae and there is no infiltration of neutrophils in the epidermis, which is classic in psoriasis.¹⁵ 


In this case the patient was treated with oral acitretin. After 2 months of acitretin therapy he had moderate improvement, and was completely disease-free after 9 months of treatment.


CASE #2

Psoriasis is a common inflammatory skin disease characterized by erythematous scaly papules and plaques that tend to localize to the elbows, knees, and scalp but may be generalized. Psoriasis is a chronic dermatosis with a strong genetic basis and several clinical subtypes. 

It is an immune-mediated disease in which infiltrates of activated T cells are thought to stimulate keratinocyte hyperproliferation, causing abnormal growth and differentiation of the epidermis. 


Psoriasis occurs worldwide and affects both sexes equally.¹⁷ In the United States, approximately 2% to 3% of the population, including more than 7 million adults, have a diagnosis of psoriasis.^17,18 Prevalence varies among different population-based studies but tends to rise with increasing distance from the equator.^18,19 


Psoriasis can occur at any age, with most patients experiencing initial presentation between ages 15 and 30 years.¹⁷ Earlier onset of disease and a positive family history of psoriasis predispose an individual to a more extensive and recurrent condition.


The pathogenesis of psoriasis involves abnormal growth of the epidermis, T-cell infiltrates in lesions, altered keratinocyte kinetics, and vascular changes.²⁰ The hyperproliferative epidermis is characterized by overabundance of epidermal stem cells and highly mitotic keratinocytes with shortened life cycles.

Altered maturation of keratinocytes is induced by an inflammatory cascade in the dermis involving complex interplay of T cells, dendritic cells, neutrophils, and cytokines.²¹ 


Although psoriasis has an established genetic basis, its exact etiology is unknown. It is believed to be polygenic and certain HLA alleles are strongly associated with psoriasis. The psoriasis susceptibility (PSORS1) locus in the major histocompatibility complex (chromosome 6p21.3) has been identified as the major genetic determinant of the disease.^22,23 

According to population studies, the risk of psoriasis in an offspring is estimated to be 41% if both parents are affected, 14% if one parent is affected, and 6% if one sibling is affected, compared with 2% when there is no family history.²⁴ Lifestyle factors may influence the course of disease; potential environmental triggers include bacterial infection, physical trauma, psychological stress, and drugs. 

The mode of inheritance for psoriasis is most likely multifactorial, influenced by multiple genes plus environmental factors. Persons with psoriasis have increased rates of morbidity and mortality from cardiovascular events. 

Common comorbidities include malignancy, diabetes, hypertension, metabolic syndrome, and inflammatory bowel disease. Psoriasis is not life-threatening, but it can be emotionally disabling for the patient and can significantly impair quality of life due to concerns about appearance. 


Of the five major clinical subtypes of psoriasis, plaque-type psoriasis (also known as psoriasis vulgaris) is the most common form, appearing in approximately 90% of individuals with the disease.²⁴ The classic lesion of plaque-type psoriasis is a well-defined, raised, red plaque with a loosely adherent silvery white scale. Beneath the scale, the affected skin has a glossy, homogeneous erythema. Plaque-type psoriasis typically presents with a symmetrical distribution of plaques that are characteristically localized to the extensor aspects of the elbows and knees.

 Other sites of involvement are the scalp, lower back, umbilicus, buttocks, genitals, and intergluteal cleft. The lesions may range in size from pinpoint plaques to patches that cover large areas of the body. Localized small lesions may coalesce to form larger plaques in which the borders resemble a land map (psoriasis geographica). Although the plaques are usually asymptomatic, some patients complain of pruritus.


The other forms of psoriasis are guttate, erythrodermic, pustular, and inverse. Guttate psoriasis is characterized by multiple small (<1 cm in diameter) papules over the trunk and proximal extremities. It is usually self-limited and manifests as an acute eruption in early age. The onset of guttate psoriasis may be preceded by streptococcal pharyngitis. 

Erythrodermic psoriasis is associated with systemic symptoms and necessitates fast-acting treatment. It is characterized by generalized erythema and superficial scaling over the entire body surface. Acute generalized pustular psoriasis is a rare variant of psoriasis, characterized by fever lasting several days and sudden onset of widespread erythema and eruption of sterile pustules. It may lead to life-threatening complications related to hepatic abnormalities and impaired renal function. 

Inverse psoriasis refers to the reverse of the typical presentation of psoriatic lesions on extensor surfaces; plaques appear on intertriginous areas such as the axilla and the inguinal region.


Extracutaneous manifestations of psoriasis include arthritis and changes in appearance of the nails. Nail changes are found in up to 40% of psoriasis patients, increasing in incidence with age, duration and extent of disease, and presence of psoriatic arthritis.²⁵ 

Several distinct features involving abnormalities of the nail matrix or nail bed have been described, including pitting, subungual hyperkeratosis, onychodystrophy, and oil drop spotting. Psoriatic arthritis occurs in 10% to 25% of patients with psoriasis.²⁴ Subtypes of psoriatic arthritis include distal arthritis, arthritis mutilans, and spondyloarthropathy. 


The diagnosis of psoriasis is usually based on easily recognized clinical features. If physical examination is not diagnostic, a punch biopsy from involved skin is indicated to rule out other conditions. Histologically, psoriatic lesions demonstrate epidermal hyperplasia, prominent rete ridges, parakeratosis, epidermal and perivascular dermal infiltrates of lymphocytes, spotty loss of the granular cell layer, and increased mitosis of keratinocytes.^24,26


The differential diagnosis of psoriasis includes skin conditions that also present with thick plaques: seborrheic dermatitis, discoid eczema (nummular dermatitis), pityriasis rubra pilaris (PRP), tinea corporis, and cutaneous T-cell lymphoma, among others.²⁴ 

Seborrheic dermatitis is characterized by erythematous patches covered by greasy scales and less prominent induration than in psoriasis. Discoid eczema manifests as coin-shaped sores that leak fluid and become crusty. PRP is a rare papulosquamous disorder characterized by follicular hyperkeratotic papules that spread cephalocaudally. 

Typical manifestation of PRP is red-orange scaling with sharply demarcated islands of normal skin. Features that suggest psoriasis are a positive family history, no pruritus, and localization of lesions to extensor surfaces.²⁶


There is no prevention or cure for psoriasis, but it can be managed with topical agents for mild disease, phototherapy for moderate disease, or immune-modulating systemic treatments for severe disease.²⁷ Most cases of psoriasis are treated topically with corticosteroids, vitamin D analogs, tazarotene, or calcineurin inhibitors. Immunosuppressive medications include cyclosporin A and methotrexate. 

Oral retinoids are particularly useful for the palmoplantar and pustular subtypes of psoriasis. Ultraviolet radiation for widespread psoriasis may act through anti-inflammatory effects to inhibit T-cell activation in plaques.²⁸ Treatment modalities should be chosen on the basis of type of psoriasis, disease severity, extent of involvement, and relevant comorbidities. 


In this case, the patient was started on adalimumab 40 mg, injected subcutaneously every 2 weeks. By the third month of treatment his skin was completely clear and he reported significant improvement in his depression.

Julie Kim Nguyen and Nrithya Pavarthi Sundararaman are medical students at Baylor College of Medicine in Houston, where Adam Rees, MD, is a dermatology resident.


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HOW TO TAKE THE POST-TEST: This Clinical Advisor CME activity consists of 3 articles.To obtain credit, you must also read Flat-topped papules on a child’s trunk and Multiple blisters on the extremities. Then take the post-test here.

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References


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8. 8. Martinez Calixto LE, Suresh L, Matsumura E, et al. Oral pityriasis rubra pilaris. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101(5):604-607.

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17. Weigle N, McBane S. Psoriasis. >Am Fam Physician. 2013;87(9):626-633. Available at www.aafp.org/afp/2013/0501/p626.html.
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19. Rachakonda TD, Schupp CW, Armstrong AW. Psoriasis prevalence among adults in the United States. J Am Acad Dermatol. 2014;70(3):512-516.

20. Nickoloff BJ, Nestle FO. Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities. J Clin Invest. 2004;113(12):1664-1675. Available at www.ncbi.nlm.nih.gov/pubmed/15199399. 

21. Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med. 2009;361(5):496-509.

22. Trembath RC, Clough RL, Rosbotham JL, et al. Identification of a major susceptibility locus on chromosome 6p and evidence for further disease loci revealed by a two stage genome-wide search in psoriasis. Hum Mol Genet.1997;6(5):813-820. Available at hmg.oxfordjournals.org/content/6/5/813.long. 

23. Sagoo GS, Cork MJ, Patel R, Tazi-Ahnini R. Genome-wide studies of psoriasis susceptibility loci: a review. J Dermatol Sci. 2004;35(3):171-179.

24. Lowell GA, Katz SI, Gilchrest BA, et al. Psoriasis. Fitzpatrick’s Dermatology in General Medicine>. 8th ed. New York, N.Y.:The McGraw-Hill Companies, Inc.; 2012:chap 18.

25. van der Velden HM, Klaassen KM, van de Kerkhof PC, Pasch MC. Fingernail psoriasis reconsidered: a case-control study. J Am Acad Dermatol. 2013;69(2):245-252. 

26. Wolff K, Johnson RA, Saavedra AP. Psoriasis and Psoriasiform Dermatoses.Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology. 7th ed. New York, N.Y.: McGraw-Hill Education; 2013:section 3.

27. Menter A, Griffiths CE. Current and future management of psoriasis.Lancet. 2007;370(9583):272-284.

28. Tartar D, Bhutani T, Huynh M, et al. Update on the immunological mechanism of action behind phototherapy. J Drugs Dermatol. 2014;13(5):564-568.


All electronic documents accessed July 9, 2014