Pathogenesis

Understanding of the immune mechanism of disease has led to a burgeoning of target therapies. Psoriasis is an autoimmune disorder driven in large part by T cells (see Fig. 8.1 ). Various inflammatory pathways are important in the pathogenesis of various forms of psoriasis and form the basis for molecular targeted therapies ( Fig. 8.1 and Tables 8.1 and 8.2 ).

Inflammatory pathways in the pathogenesis of psoriasis. Psoriasis is mediated by the aberrant activation of dermal dendritic cells (DCs) producing TNF and IL-23. These DCs stimulate autoimmune Th17 and Tc17 cells to migrate into the epidermis, where they recognize epidermal autoantigens and produce Th17 cytokines IL-17 and IL-22. Th17 cytokines trigger the epidermal phenotype of plaque psoriasis, characterized by an abnormal keratinocyte hyperproliferation and the activation of keratinocytes to produce antimicrobial peptides (AMP) and chemokines. The TNF–IL-23–Th17 pathway appears to be central in the pathogenesis of chronic plaque psoriasis (central portion of the figure). Another inflammatory pathway, mediated by plasmacytoid dendritic cells (pDCs) producing large amounts of type I IFNs, has emerged by studying early events in the pathogenesis of psoriasis. The pDC–IFN pathway is dominant in acute forms of psoriasis such as erythrodermic psoriasis (left part of the figure). Finally, analysis of pustular psoriasis has revealed that neutrophil infiltration triggered by IL-17 is central for the cleavage and activity of IL-36, which in turn induces IL-1 production by DCs and further stimulates Th17 polarization. The IL-36–IL-1 pathway appears to be dominant in pustular psoriasis (right part of the figure).

(From Conrad C, Gilliet M. Psoriasis: from pathogenesis to targeted therapies. Clin Rev Allergy Immunol 2018;54(1):102–13.)

Clinical Manifestations

The lesions of psoriasis are distinctive. They begin as red, scaling papules that coalesce to form round to oval plaques, which can easily be distinguished from the surrounding normal skin ( Fig. 8.2 ). The scale is adherent and silvery white, and reveals bleeding points when removed (Auspitz sign). Scale may become extremely dense, especially on the scalp. Scale forms but is macerated and dispersed in intertriginous areas; therefore the psoriatic plaques of skin folds appear as smooth, red plaques with a macerated surface. The most common site for an intertriginous plaque is the intergluteal fold; this is referred to as gluteal pinking ( Figs. 8.3 and 8.4 ). The deep, rich red color is another characteristic feature and remains constant in all areas.

Psoriasis. Typical oval plaque with well-defined borders and silvery scale.

Psoriasis. Gluteal pinking, a common lesion in patients with psoriasis. Intertriginous psoriatic plaques retain the rich red color typical of skin lesions but do not retain scale.

Psoriasis. Psoriasis often involves the gluteal cleft. Hydrocortisone–iodoquinol is usually effective in controlling gluteal cleft psoriasis.

Psoriasis can develop at the site of physical trauma (scratching, sunburn, or surgery), the so-called isomorphic or Koebner phenomenon ( Fig. 8.5 ; see also Figs. 8.12 and 8.14 ). Pruritus is highly variable. Although psoriasis can affect any cutaneous surface, certain areas are favored and should be examined in all patients in whom the diagnosis of psoriasis is suspected. Those areas are the elbows, knees, scalp, gluteal cleft, fingernails, and toenails.

Psoriasis. Koebner phenomenon. Psoriasis has appeared on the donor site of the skin graft.

The disease affects the extensor more than the flexor surfaces and usually spares the palms, soles, and face. Most patients have chronic localized disease, but there are several other presentations. Localized plaques may be confused with eczema or seborrheic dermatitis (SD), and the guttate form with many small lesions can resemble secondary syphilis or pityriasis rosea (PR).

Comorbidities Associated With Psoriasis

The concurrence of multiple diseases or disorders in association with a given disease (i.e., comorbidity) has been observed in psoriasis. Compared to the general population, patients with psoriasis are at a higher risk for comorbidities such as arthritis, heart disease, diabetes, cancer, and hypertension ( Table 8.5 ).

Comorbidities tend to increase with age. Nearly half of psoriasis patients aged over 65 years have at least three comorbidities and two thirds have two or more comorbidities.

Clinical Presentations

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  Variations in the morphology of psoriasis

  
  
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  Chronic plaque psoriasis

  
  
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  Guttate psoriasis (acute eruptive psoriasis)

  
  
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  Pustular psoriasis

  
  
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  Erythrodermic psoriasis

  
  
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  Light-sensitive psoriasis

  
  
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  HIV-induced psoriasis

  
  
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  Keratoderma blennorrhagicum (Reiter syndrome)

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  Variations in the location of psoriasis

  
  
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  Scalp psoriasis

  
  
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  Psoriasis of the palms and soles

  
  
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  Pustular psoriasis of the palms and soles

  
  
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  Pustular psoriasis of the digits

  
  
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  Psoriasis inversus (psoriasis of flexural areas)

  
  
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  Psoriasis of the penis and Reiter syndrome

  
  
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  Nail psoriasis

  
  
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  Psoriatic arthritis

Chronic Plaque Psoriasis

Chronic, noninflammatory, well-defined plaques are the most common presentation of psoriasis. The plaques are irregular, round to oval, with a predilection for extensor surfaces such as the elbows and knees. Plaques have a silvery surface scale and tend to be symmetrically distributed. They can appear anywhere on the skin surface. Plaques enlarge and then tend to remain stable for months or years ( Figs. 8.6 and 8.7 ). Smaller plaques or papules may coalesce into larger lesions. Numerous lesions may cover almost the entire body surface. A temporary brown, white, or red macule remains when the plaque subsides.

A, Chronic plaque psoriasis. Noninflamed plaques tend to remain fixed in position for months. B, Plaques are more inflamed than on the patient in A.

A–B, Generalized plaque psoriasis.

Guttate Psoriasis

More than 30% of psoriatic patients have their first episode before age 20; in many instances, an episode of guttate psoriasis is the first indication of the patient’s propensity for the disease. Streptococcal pharyngitis or a viral upper respiratory tract infection may precede the eruption by 1 or 2 weeks. Scaling papules suddenly appear on the trunk and extremities, not including the palms and soles ( Figs. 8.8 and 8.9 ). Their number ranges from a few to many, and their size may be that of a pinpoint up to 1 cm. Lesions increase in diameter with time. The scalp and face may also be involved. Pruritus is variable. Guttate psoriasis may resolve spontaneously in weeks or months; it responds more readily to treatment than does chronic plaque psoriasis. Throat cultures should be taken to rule out streptococcal infection. Infected patients are treated for 10 days with penicillin or amoxicillin. Penicillin-allergic individuals are treated with a first-generation cephalosporin for 10 days, clindamycin or clarithromycin for 10 days, or azithromycin for 5 days.

Guttate psoriasis. A, Acute lesions have little scale. B, Numerous, uniformly small lesions may abruptly occur following streptococcal pharyngitis. C, Numerous plaques appeared without a history of streptococcal infection. D, Plaques have increased in size with time. E, Pinpoint to 1-cm lesions develop typical psoriatic scale soon after appearance.

Guttate psoriasis. A–D, This 8-year-old girl developed guttate psoriasis after streptococcal pharyngitis.

Generalized Pustular Psoriasis

This rare form of psoriasis is a serious and sometimes fatal multisystem disorder. Erythema suddenly appears in the flexural areas and migrates to other body surfaces. Numerous tiny, sterile pustules evolve from an erythematous base and coalesce into lakes of pus ( Fig. 8.10 ). The superficial, upper epidermal pustules are easily ruptured. Many patients are weak, febrile (temperatures up to 40° C) with arthralgia and myalgia. Laboratory abnormalities include elevated white blood cell count, with neutrophilia, C-reactive protein, and liver enzymes. Patients exhibit osteoarthritis, uveitis, neutrophilic cholangitis, acute respiratory distress syndrome, and cardiovascular shock. Rarely, familial cases of pustular psoriasis have been identified and homozygous and composite heterozygote loss of function mutations in the IL36R gene have been found. This genetic mutation is not seen in patients with plaque psoriasis without pustules, but may be seen in patients with palmar–plantar psoriasis (see below), acrodermatitis continua of Hallopeau (rare relapsing pustular psoriasis variant, involving distal hands and feet, may have bony changes), and acute generalized exanthematous pustular eruption. Patients with generalized pustular psoriasis and palmar plantar psoriasis have also been found to have CARD14 (caspase-activating recruitment domain, member 14) mutations. Pustular flares occur with infection, emotional stress, withdrawal from topical and systemic steroids, and pregnancy. Topical medications such as tar and anthralin may precipitate episodes in patients with unstable or labile plaque psoriasis. Wet dressings and group V topical steroids provide initial control. Acitretin, cyclosporine (CS), methotrexate (MTX), and infliximab are first-line therapies for those with generalized pustular psoriasis. They provide rapid relief in just a few days. Adalimumab, etanercept, and psoralen plus ultraviolet (UV) A light are second-line modalities.

Generalized pustular psoriasis. An erythematous plaque has evolved into numerous sterile pustules, which have coalesced in many areas.

Erythrodermic Psoriasis

Generalized erythrodermic psoriasis, like generalized pustular psoriasis, is a severe, unstable, highly labile disease that may appear as the initial manifestation of psoriasis but usually occurs in patients with previous chronic disease ( Fig. 8.11 ). Precipitating factors include the administration of systemic corticosteroids; the excessive use of topical steroids; the overzealous application of irritating topical therapy; and the consequences of phototherapy complications, severe emotional stress, and preceding illness, such as an infection. Discontinuation of CS, MTX, and ixekizumab have also resulted in erythrodermic psoriasis. Treatment includes bed rest, initial avoidance of all UV light, utilization of Burow’s solution compresses or colloidal oatmeal baths, liberal use of emollients, increased intake of protein and fluids, administration of antihistamines for pruritus, avoidance of potent topical steroids, and, in severe cases, hospitalization.

Psoriatic erythroderma. Generalized erythema occurred shortly after this patient discontinued use of methotrexate.

Cyclosporine and infliximab are the most rapidly acting agents. Acitretin and MTX are also appropriate first-line choices, although they usually work more slowly. Second-line agents include etanercept or combination therapy. Tar and anthralin may exacerbate the disease and should be avoided.

Light-Sensitive Psoriasis

Psoriatic patients wait for sunny summer months when, in most cases, the disease responds predictably to ultraviolet light. However, too much of a good thing can be dangerous, especially for the patient who gets sunburned in an anxious attempt to clear the disease rapidly. As a result of the Koebner phenomenon, guttate lesions or a painful, diffusely inflamed plaque forms in the burned areas ( Fig. 8.12 ). Plaques subsequently converge onto the clear, previously protected sites. Some patients do not tolerate ultraviolet light of any intensity.

Light-induced psoriasis. Overexposure to sunlight precipitated this diffuse flare of psoriasis. The mid-back was protected by a wide halter strap.

Psoriasis of the Scalp

The scalp is a favored site for psoriasis and may be the only site affected. Plaques are similar to those of the skin except that the scale is more readily retained; it is anchored by hair. Extension of the plaques onto the forehead is relatively common ( Fig. 8.13 ). A dense, tight-feeling scale can cover the entire scalp. Even in the most severe cases, the hair is not permanently lost. Permanent hair loss may occur if scale is chronically removed along with the hair. Scalp psoriasis can be persistent and recalcitrant to therapy. A distinct scaling eruption of the scalp observed in children is described in this chapter in the section concerning SD.

Psoriasis of the scalp. Plaques typically form in the scalp and along the hair margin. Occasionally plaques occur on the face.

Psoriasis of the Palms and Soles

The palms and soles may be involved as part of a generalized eruption, or they may be the only locations involved in the manifestation of the disease. There are several presentations. Superficial red plaques with thick brown scale may be indistinguishable from chronic eczema ( Fig. 8.14 ). Smooth, deep red plaques are similar to those found in the flexural area ( Fig. 8.15 ).

Psoriasis of the fingertips. The eruption appears eczematous, but the rich red hue is typical of psoriasis. This eruption occurred as a Koebner phenomenon in a surgeon.

Psoriasis of the hand. Deep red, smooth plaque in a patient with typical lesions on the body.

Pustular Psoriasis of the Palms and Soles

Deep pustules first appear on the middle portion of the palms and insteps of the soles; they may either remain localized or spread ( Figs. 8.16 and 8.17 ). The pustules do not rupture but turn dark brown and scaly as they reach the surface. The surrounding skin becomes pink, smooth, and tender. A thick crust may later cover the affected area. The course is chronic, lasting for years while the patient endures periods of partial remission followed by exacerbations so painful that mobility is affected. There is a considerably higher prevalence of smoking in these patients. Acitretin, MTX, psoralen plus ultraviolet light A (PUVA), narrowband ultraviolet light B light (NB-UVB), and intermittent courses of topical steroids under plastic occlusions are therapeutic alternatives.

Pustular psoriasis. A–B, Pustular psoriasis of the palms responds well to cyclosporine or acitretin.

Pustular psoriasis of the soles. A, An early case in a typical location. B, This is a chronic disease in which the soles may remain inflamed for years.

Keratoderma Blennorrhagicum (Reiter Syndrome)

Reiter syndrome appears to be a reactive immune response that is usually triggered in a genetically susceptible individual (60% to 90% of patients are HLA-B27 positive) by any of several different infections, especially those that cause dysentery or urethritis, such as Yersinia enterocolitica and Yersinia pseudotuberculosis . Psoriasiform skin lesions develop in patients with Reiter syndrome (urethritis and/or cervicitis, peripheral arthritis of more than 1 month’s duration) usually 1 to 2 months after the onset of arthritis; conjunctivitis develops in 25% of patients. The distinctive lesions, keratoderma blennorrhagica, typically appear on the soles ( Fig. 8.18A ) and extend onto the toes ( Fig. 8.18B ) but also occur on the legs, scalp, and hands. Nail dystrophy, thickening, and destruction occur. The plaques are psoriasiform with a distinctive circular, scaly border ( Fig. 8.19 ). The scaly, scalloped-edged plaques develop from coalescence of expanding papulovesicular plaques with thickened yellow, heaped-up scale. Similar lesions occur on the penis. Skin and joint symptoms have responded to MTX, acitretin, and ketoconazole.

Keratoderma blennorrhagicum (Reiter syndrome). A, The palms and soles are commonly involved. There are keratotic papules, plaques, and pustules that coalesce to form circular borders like those seen on the penis (see Fig. 8.21 ). B, Psoriasiform plaques develop from coalescence of expanding papulovesicular plaques and are typically found on the soles and toes.

Patients with Reiter syndrome develop psoriasiform skin lesions (keratoderma blennorrhagica) with a distinctive circular, scaly border. These distinctive lesions occur most frequently on the soles and toes.

Psoriasis of the Penis and Reiter Syndrome

Typical psoriatic scaling plaques with white scale can appear on the body and circumcised penis ( Fig. 8.20 ). Scale does not form when the penis is covered by a foreskin. A highly characteristic psoriasiform lesion, balanitis circinata, occurs in Reiter syndrome when erosions covered by scale and crust on the corona and glans coalesce to form a distinctive winding pattern ( Fig. 8.21 ). A biopsy helps confirm the diagnosis. A potassium hydroxide examination excludes Candida infection.

Psoriasis. Typical psoriatic scaling plaques with white scale can appear on the circumcised penis. Scale does not form when the penis is covered by foreskin.

Reiter syndrome. Balanitis circinata, a highly characteristic psoriasiform lesion, occurs in Reiter syndrome when erosions covered by scale and crust on the corona and glans coalesce to form a distinctive winding pattern.

Pustular Psoriasis of the Digits

This severe localized variant of psoriasis, also known as acrodermatitis continua of Hallopeau (see Generalized Pustular Psoriasis ), may remain localized to one finger for years. Vesicles rupture, resulting in a tender, diffusely eroded, and fissured surface that continually exudes serum. The loosely adherent, moist crust is easily shed, but recurs ( Fig. 8.22 ). Localized pustular psoriasis is very resistant to therapy.

Pustular psoriasis of the digits. The eruption has remained localized in this one finger for years.

Human Immunodeficiency Virus (HIV)–Induced Psoriasis

Psoriasis may be the first or one of the first signs of human immunodeficiency virus (HIV) infection. Psoriasis in the setting of HIV may be mild, moderate, or severe. It can be atypical and unusually severe with involvement of the groin, axilla, scalp, palms, and soles. An explosive onset with erythroderma or pustular lesions that rapidly become confluent should lead one to suspect HIV. Treatment of psoriasis in the setting of HIV is challenging because the depleted T cells in HIV may be worsened by systemic psoriasis therapy. Topical steroids and vitamin D analogues (see Formulary) may be utilized for mild limited plaque psoriasis. Phototherapy, such as NB-UVB and antiretroviral therapy are the first-line therapy for moderate to severe psoriasis. Acitretin may be utilized next and third-line therapies for recalcitrant psoriasis include CS, MTX, and tumor necrosis factor (TNF)-α inhibitors. Apremilast has been utilized as well for severely affected patients. The efficacy and safety of biologic agents in the treatment of HIV-infected individual is unknown, since HIV-infected individuals are not included in clinical trials.

Psoriasis Inversus (Psoriasis of the Flexural or Intertriginous Areas)

The gluteal fold, axillae, groin, submammary folds, retroauricular fold, and the glans of the uncircumcised penis may be affected. The deep red, smooth, glistening plaques may extend to and stop at the junction of the skin folds, as with intertrigo or Candida infections. The surface is moist and contains macerated white debris. Infection, friction, and heat may induce flexural psoriasis, a Koebner phenomenon. Cracking and fissures are common at the base of the crease, particularly in the groin, gluteal cleft, and superior and posterior auricular folds ( Figs. 8.23 to 8.26 ). As with typical psoriatic plaques, the margin is distinct. Pustules beyond the plaque border suggest secondary yeast infection. Infants and young children may develop flexural psoriasis of the groin that extends onto the diaper area.

Psoriasis of the posterior auricular fold.

Psoriasis of the vulva is frequently misdiagnosed as Candida infection. The diagnosis becomes apparent when topical and oral anti-yeast medications fail.

Inverse psoriasis. Plaques are red and symmetric. The differential diagnosis includes Candida infection and intertrigo.

Inverse psoriasis. Many clinicians would make the diagnosis of Candida infection. The patient’s history of psoriasis suggested the diagnosis.

Psoriasis of the Nails

Nail changes are characteristic of psoriasis and the nails of patients should be examined (see Chapter 25 ). These changes offer supporting evidence for the diagnosis of psoriasis when skin changes are equivocal or absent.

Onycholysis.

Psoriasis of the nail bed causes separation of the nail from the nail bed. Unlike the uniform separation caused by pressure on the tips of long nails, the nail detaches in an irregular manner. The nail plate turns yellow, simulating a fungal infection ( Fig. 8.27 ).

Separation of the nail, or onycholysis, is accompanied by yellow discoloration. Scaly debris elevates the nail plate. The debris is commonly mistaken for nail fungal infection.

Subungual Debris.

This is analogous to fungal infection; the nail bed scale is retained, forcing the distal nail to separate from the nail bed (see Fig. 8.27 ).

Pitting.

Nail pitting is the best known and possibly the most frequent psoriatic nail abnormality ( Figs. 8.28 and 8.29 ). Nail plate cells are shed in much the same way as psoriatic scale is shed, leaving a variable number of tiny, punched-out depressions on the nail plate surface. They emerge from under the cuticle and grow out with the nail. Many other cutaneous diseases may cause pitting (e.g., eczema, fungal infections, and alopecia areata), or it may occur as an isolated finding as a normal variation.

Pitting psoriasis of the proximal nail matrix results in loss of parakeratotic cells from the surface of the nail plate. This is a process analogous to the shedding of psoriatic skin scale.

Oil spot lesion. A translucent yellow-red discoloration resembles a drop of oil beneath the nail plate. It occurs from psoriasis of the nail bed, which causes serum to be trapped under the nail plate.

Oil Spot Lesion.

Psoriasis of the nail bed may cause localized separation of the nail plate. Cellular debris and serum accumulate in this space. The brown-yellow color observed through the nail plate looks like a spot of oil (see Fig. 8.29 ).

Nail Deformity.

Extensive involvement of the nail matrix results in a nail losing its structural integrity, resulting in fragmentation and crumbling.

Psoriatic Arthritis

Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy of the peripheral joints, spine, and entheses; it is associated with psoriasis in which rheumatoid factor (RF) and anti–cyclic citrullinated peptide (anti-CCP) measurements are usually negative . It may precede, accompany, or, more often, follow the skin manifestations. Onset may occur at any age, but peak occurrence is between ages 20 and 40; women and men are equally affected. Symmetric polyarthritis with joint pain and joint swelling often indicates erosive progressive disease. Unlike in rheumatoid arthritis (RA), the distal interphalangeal (DIP) joints are regularly involved. The presence of inflammatory arthritis in patients with psoriasis varies between 5% and 42%. Approximately 15% of patients with PsA have an onset of arthritis before the onset of psoriasis. The prevalence of PsA is higher among patients with more severe cutaneous disease. Nail involvement occurs in more than 80% of patients with PsA, compared with 30% of patients with uncomplicated psoriasis ( Fig. 8.30 ). The prevalence of nail psoriasis is highest among patients with PsA who have arthritic involvement of their fingers, but the presence of nail disease does not have predictive value in determining if a patient is at risk for PsA. Cases of arthritis have been reported to develop following trauma. Patients with PsA who become pregnant improve or even show diminishment of symptoms in 80% of cases. Despite active treatment and a reduction in joint inflammation and the rate of damage, PsA may be a progressively deforming arthritis. Fig. 8.31 highlights the key cell types and inflammatory pathways involved with PsA.

Nail psoriasis. This patient with nail psoriasis responded well to apremilast.

Key cell types and secretion of key inflammatory mediators in psoriatic arthritis. T-cell subpopulations Th1, Th2, Th17, Th9, Th22, and Treg cells secrete proinflammatory or antiinflammatory cytokines. Dendritic cells, macrophages, ILCs, MAIT cells, NK cells, and mast cells produce mostly proinflammatory cytokines. These proinflammatory mediators activate resident cells, including synovial fibroblasts, chondrocytes, and osteoblasts, which in turn secrete more proinflammatory mediators that can further recruit immune cells into the joins, creating a self-perpetuating inflammatory response. Additionally, synovial fibroblasts secrete matrix-degrading enzymes and RANKL, resulting in cartilage degradation and bone resorption. The inflamed synovial microenvironment leads to the formation of the synovial pannus, entheseal inflammation, and joint destruction. ADAMTS, ADAM metallopeptidase with thrombospondin type 1 motif; GM-CSF, granulocyte–macrophage colony-stimulating factor; IFN-γ, interferon γ; IL, interleukin; ILC, innate lymphoid cell; MAIT, mucosal-associated invariant T; MIF, macrophage migration inhibitory factor; MMPs, matrix metalloproteinases; NK, natural killer; NO, nitric oxide; OSM, oncostatin M; RANKL, TNF superfamily member 11; RANTES, C-C motif chemokine ligand 5; ROS, reactive oxygen species; TGF-β, transforming growth factor β; Th, T-helper cell; TNF-α, tumor necrosis factor α; Treg, regulatory T cell.

(From Veale DJ, Fearon U. The pathogenesis of psoriatic arthritis. Lancet 2018;391(10136):2273–84.)

Defining Psoriatic Arthritis (PsA)

The spondyloarthritis (SpA) family of diseases includes PsA, RA, ankylosing spondylitis (AS), reactive arthritis, and enteropathic arthritis. PsA is characterized by infrequent seropositivity for RF and anti-CCP, and an association with HLA-B27 alleles, particularly in those patients with axial involvement.

Other features can include enthesitis, dactylitis, iritis, peripheral arthritis (oligoarticular asymmetric and polyarticular symmetric), spondylitis, and a variable clinical course. The heterogeneity in clinical presentation and course makes PsA difficult to classify and differentiate from other forms of SpA and inflammatory arthropathies.

Dactylitis presents as the “sausage digit” – diffuse swelling of the entire digit. Enthesitis – inflammation at the site of ligamentous and tendinous insertion – is characteristic of all the HLA-B27-associated spondyloarthropathies.

Clinical Features.

There are five recognized presentations of PsA ( Fig. 8.32 ).

Signs and symptoms of psoriatic arthritis. A, Pitting, onycholysis, brown nail bed stain. B, Swollen finger joints. C–D, Sausage finger and sausage toe (dactylitis). E, Swollen heel at the Achilles tendon (enthesitis).

The most common pattern is an asymmetric arthritis involving one or more joints of the fingers and toes ( Fig. 8.33 ). Usually one or more proximal interphalangeal (PIP), DIP, metatarsophalangeal, or metacarpophalangeal joints are involved. During the acute phase, the joint is red, warm, and painful. Continued inflammation promotes soft tissue swelling on either side of the joint (“sausage finger”) and restricts mobility. HLA-DR7 level is significantly increased in this group with peripheral arthritis.

Psoriatic arthritis. Asymmetric arthritis pattern.

Moll and Wright Classification.

The Moll and Wright classification was developed more than 30 years ago and is still used today to divide PsA into five clinical subtypes ( Table 8.6 ). These patterns are often mixed and not well defined.

TABLE 8.6

Moll and Wright Clinical Subtypes for Psoriatic Arthritis *

Type	Percentage of All Psoriatic Arthritis Patients	Features
Oligoarticular, asymmetric arthritis (one or more joints)	30–50	Joints of fingers and toes (“sausage finger”) are involved.
Polyarticular, symmetric arthritis (RA-like)	30–50	Clinically resembles rheumatoid arthritis, rheumatoid factor negative. The small joints of the hands and feet, wrists, ankles, knees, and elbows may be involved.
Distal interphalangeal joint predominant	25	Mild, chronic, nondebilitating, and associated with nail disease. Involves hands and feet. This is the most characteristic presentation of arthritis with psoriasis.
Destructive polyarthritis (arthritis mutilans)	5	The most severe form of psoriatic arthritis involves osteolysis of any of the small bones of the hands and feet. Gross deformity and subluxation are attributed to this condition. Severe osteolysis leads to digital telescoping, producing the “opera glass” deformity. This deformity may be seen in rheumatoid arthritis.
Ankylosing spondylitis and sacroiliitis	30–35	Occurs as an isolated phenomenon or in association with peripheral joint disease. Association of HLA-B27 and spondylitis. The strongest association is in males with sacroiliitis. Asymptomatic sacroiliitis occurs in as many as one third of cases of psoriasis. It is usually asymmetric and may be associated with spondylitis.

 

* To meet the Moll and Wright 1973 classification criteria for psoriatic arthritis, a patient with psoriasis and inflammatory arthritis who is seronegative for rheumatoid arthritis (RA) must present with one of the above five clinical subtypes. Criteria specificity is 98% and sensitivity is 91%.

Classification Criteria for Psoriatic Arthritis (CASPAR).

A new Classification Criteria for Psoriatic Arthritis (CASPAR) was published by the Classification Criteria for Psoriatic Arthritis Study Group ( Table 8.7 ). These criteria were established for patients with long-standing disease duration (mean, 12.5 years). Classification criteria are not yet validated for early disease.

TABLE 8.7

CASPAR Criteria for Psoriatic Arthritis *

From Rudwaleit M, Taylor WJ. Classification criteria for psoriatic arthritis and ankylosing spondylitis/axial spondyloarthritis. Best Pract Res Clin Rheumatol 2010;24(5):589–604.

Inflammatory articular disease (joint, spine, or entheseal) plus the following:
Clinical Finding	Score
Psoriasis	Current (2), history of (1), family history of (1); patient-reported history in a first- or second-degree relative
Nail dystrophy	(1) Including onycholysis, pitting, and hyperkeratosis
Negative rheumatoid factor	(1)
Dactylitis	Current (1), history of (1); defined as swelling of an entire digit, or a history of dactylitis recorded by a rheumatologist
Radiographic evidence	Juxtaarticular new bone formation, appearing as ill-defined ossification near joint margins (but excluding osteophyte formation) on plain radiographs of the hand (1)

 

* To meet the Classification Criteria for Psoriatic Arthritis (CASPAR, 2006), a patient must have inflammatory articular disease and 3 points from the remaining categories; the assigned scores are in parentheses. Criteria specificity is 98.7% and sensitivity is 91.4%.

Differentiating PsA and Rheumatoid Arthritis (RA)

PsA affects men and women equally; RA affects women more commonly ( Table 8.8 ). RA affects metacarpophalangeal and PIP joints; PsA affects the DIP joints in at least 50% of patients. RA tends to have a symmetric distribution, PsA an asymmetric distribution. PsA often affects all joints of the same digit, leading to a “ray” distribution. The affected joints of patients with PsA are less tender than in patients with RA. The spine is not affected in RA; 50% of PsA patients have spinal involvement manifested as sacroiliitis and/or syndesmophytes. Enthesitis and dactylitis are features of PsA. Skin psoriasis is a defining feature of PsA. Psoriatic arthritis occurs in 2% to 3% of patients with RA, the same frequency as in the general population. Nail lesions are more common in patients with PsA than in patients with just cutaneous psoriasis.

Differentiating PsA From Osteoarthritis (OA) and Gout

The presence of DIP involvement requires differentiation between PsA and OA (see Table 8.8 ). PsA is inflammatory; OA is usually not. Gout is often associated with periarticular inflammation, which is not seen in PsA. Sometimes large nodules (tophi) filled with uric acid crystals are seen in gout ( Fig. 8.34 ). Tophi may look like rheumatoid nodules or lipomas.

Gouty tophus. This patient with gout has a large gouty tophus on the elbow.

Differentiating Psoriatic Arthritis From Other Spondyloarthropathies.

The spondylitis seen in PsA is not as severe as with AS. Patients with PsA have better mobility and less grade 4 sacroiliitis than patients with AS ( Table 8.9 ). Peripheral arthritis is more common among patients with PsA. Only 2% of patients with PsA have isolated spinal involvement, whereas 10% of patients diagnosed with AS have psoriasis.

TABLE 8.9

Differentiating Psoriatic Arthritis From Other Spondyloarthropathies

Adapted from Gladman DD. Clinical, radiological, and functional assessment in psoriatic arthritis: is it different from other inflammatory joint diseases? Ann Rheum Dis 2006;65(Suppl. 3):iii22–4.

Feature	Psoriatic Arthritis	Ankylosing Spondylitis	Reactive Arthritis	Inflammatory Bowel Disease
Male to female ratio	1 : 1	3 : 1	8 : 1	1 : 1
Age at onset (years)	35–45	20	20	Any
Peripheral distribution	96% Any	25% Axial Lower limbs	90% Lower limbs	Common Lower limbs
Dactylitis	35%	Uncommon	Common	Uncommon
Enthesitis	Common	Common	Common	Uncommon
Sacroiliitis	50%	100%	80%	20%
Syndesmophytes	Classic and paramarginal	Classic	Classic and paramarginal	Classic
HLA-B	50%	>90%	80%	40%
Psoriasis	Always	Uncommon	Uncommon	Uncommon
Other skin lesions	Nail changes	Uncommon	Keratoderma blennorrhagica	Erythema nodosum, pyoderma gangrenosum
Quality of life	Reduced	Reduced	Likely reduced	Reduced
Function	Reduced	Reduced	Reduced	Reduced

 

Laboratory Tests.

There are no laboratory tests that specify a diagnosis of PsA. PsA patients have normal acute phase reactants, 4.6% are RF positive, and 7.6% are anti-CCP antibody positive. Erythrocyte sedimentation rate (ESR) is the best laboratory guide to disease activity ( Table 8.10 ).

TABLE 8.10

Laboratory Evaluations in Psoriatic Arthritis and in Types of Arthritis That May Coexist With Psoriasis or That Mimic Psoriatic Arthritis

From Garg A, Gladman D. Recognizing psoriatic arthritis in the dermatology clinic. J Am Acad Dermatol 2010;63(5):733–48; quiz 749–50.

Laboratory Test	PsA	OA	Gout	RA	AS	ReA
ESR	±	Normal	Normal (elevated during attack)	Elevated	±	±
CRP	±	Normal	Normal	Elevated	±	±
RF	Usually absent	Usually absent	Absent	Usually present	Usually absent	Usually absent
CCP Ab	Usually absent	Absent	Absent	Present	Usually absent	Usually absent
HLA-B27	15%–70%	4%–8%	4%–8%	4%–8%	90%	50%–85%
Synovial aspirate	Inflammatory	Noninflammatory	Inflammatory	Inflammatory	Inflammatory	Inflammatory

 

AS, ankylosing spondylitis; CCP, citrullinated-containing proteins; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; HLA, human leukocyte antigen; OA, osteoarthritis; PsA, psoriatic arthritis; RA, rheumatoid arthritis; ReA, reactive arthritis; RF, rheumatoid factor.

Imaging Studies.

The CASPAR study identified juxtaarticular bone formation as the only radiologic differentiation between RA and PsA. PsA patients have less severe radiologic changes compared with patients with AS. PsA shows narrowing of joint space, joint erosions, and bony proliferation. Magnetic resonance imaging and ultrasonography detect enthesitis (inflammation at the point of insertion of skeletal muscle to bone).

Treatment of Psoriatic Arthritis.

Evidence-based treatment algorithms have been published ( Table 8.11 ). A step up approach is recommended. For peripheral arthritis, conventional disease modifying antirheumatic drugs are considered early in the treatment of PsA. These drugs include MTX, leflunomide, and sulfasalazine. If conventional disease-modifying antirheumatic drugs (DMARDs) fail, TNF, IL-12/23, IL-17, and PDE4 inhibitors are prescribed. Nonsteroidal antiinflammatory agents are the mainstay of therapy and usually provide adequate control, but they do not induce remissions. They are first-line agents for mild PsA. Intraarticular injections with corticosteroids may be effective. Neither treatment is capable of inhibiting the development of structural joint damage ( Fig. 8.35 ).

TABLE 8.11

Comparison of Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and European League Against Rheumatism Simplified Treatment Algorithms

Adapted from Coates LC, Kavanaugh A, Mease PJ, et al. Group for research and assessment of psoriasis and psoriatic arthritis 2015 treatment recommendations for psoriatic arthritis. Arthritis Rheumatol 2016; 68:1060–1071; From Gossec L, Smolen JS, Ramiro S, et al. European league against rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update.

Clinical Involvement	GRAPPA	EULAR
PREDOMINANT PERIPHERAL ARTHRITIS
DMARDs naive	csDMARDs (MTX, LFN, SSZ) Poor prognostic factors: TNFi	CsDMARDs (MTX: preferred)
DMARDs failure	TNFi; IL-12–23i; IL-17i; PDE4i	Adverse prognostic factors: TNFi preferred; IL-12–23i; IL17i (bDMARDs): if TNFi contraindicated PDE4i if bDMARDs contraindicated
bDMARDs failure	Switch bDMARDs	Switch bDMARDs or PDE4i
PREDOMINANT AXIAL
NSAIDs naive	NSAIDs	NSAIDs
NSAIDs failure	TNFi; IL-12–23i; IL-17i	TNFi preferred; IL-12–23i; IL17i: if TNFi contraindicated
bDMARDSs failure	Switch bDMARDs	Switch bDMARDs
PREDOMINANT ENTHESEAL
NSAIDs naive	NSAIDs	NSAIDs
NSAIDs failure	TNFi; IL-12–23i; IL-17i; PD4i	TNFi preferred; IL-12–23i; IL-17i: if TNFi contraindicated PDE4i if bDMARDs contraindicated
bDMARDs failure	Switch bDMARDs or PDE4i	Switch bDMARDs or PDE4i

 

bDMARD, biologic DMARD; csDMARD, conventional synthetic DMARD; DMARD, disease-modifying antirheumatic drug; EULAR, European League Against Rheumatism; GRAPPA, Group for Research and Assessment of Psoriasis and Psoriatic Arthritis; IL-12–23i, interleukin 12–23 inhibitor; IL-17i, interleukin 17 inhibitor; LFN, leflunomide; MTX, methotrexate; PDE4i, phosphodiesterase 4 inhibitor; SSZ, sulfasalazine; TNFi, tumor necrosis factor inhibitor.

Algorithm for treatment of patients with psoriatic arthritis. BSA, body surface area; MTX, methotrexate; NSAIDs, nonsteroidal antiinflammatory drugs; TNF, tumor necrosis factor. *Mild psoriatic arthritis can be treated with appropriate nonsteroidal antiinflammatory agents. NSAIDs and low-dose prednisone (<10 mg/day) can be used as adjunctive therapy.

(From American Academy of Dermatology Work Group, Menter A, Korman NJ, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 6. Guidelines of care for the treatment of psoriasis and psoriatic arthritis: case-based presentations and evidence-based conclusions. J Am Acad Dermatol 2011;65(1):137–74.)

Methotrexate.

Methotrexate is an effective second-line agent for PsA. It is frequently used as the primary DMARD in PsA, because of its efficacy in treating both skin and joint involvement in patients with psoriatic disease. Pain and function improve dramatically 2 to 6 weeks after starting MTX therapy with 5 mg every 12 hours in three consecutive doses once a week. Lower dosages may not be effective. Methotrexate may also be given as a single dose or divided into two doses taken 12 hours apart. The amount is increased to 25 to 30 mg/week, until control is obtained, and then tapered to a maintenance dose of around 5 to 15 mg/week.

The risk of liver toxicity in patients undergoing long-term, low-dose MTX therapy for PsA is substantial, and that risk increases with the total cumulative dose and with heavy consumption of alcohol.

Etanercept (Enbrel), Adalimumab (Humira), Infliximab (Remicade), Golimumab (Simponi).

These anti–tumor necrosis factor (anti-TNF) agents bind and inhibit the activity of TNF. They are highly effective for PsA. The cost is very high. Guidelines for use are discussed under Treatment of Psoriasis. These agents are often combined with conventional DMARDs, particularly MTX.

Cyclosporine.

Cyclosporine at daily doses usually ranging from 1.5 to 5.0 mg/kg provides impressive relief from arthralgias and improvement of joint function (see Fig. 8.35 ).

Apremilast.

Apremilast, an oral inhibitor of phosphodiesterase, is effective for moderate to severe plaque psoriasis and PsA.

Treatment of Psoriasis

Many topical and systemic agents are available. None of the topical medications are predictably effective. Treatment dissatisfaction and nonadherence are high. All require lengthy treatment to give relief that is often temporary. Compliance is a problem. Patients become discouraged with moderately effective expensive topical treatment that lasts weeks or months. Limited disease can be managed with topical therapy ( Table 8.12 ). One intralesional steroid injection (5–10 mg/mL triamcinolone acetonide) can heal a small plaque and keep it in remission for months. This is an ideal treatment for patients with a few small plaques. Topical steroid creams and ointments, calcitriol, calcipotriene, tazarotene, and tar are the mainstays of topical treatment. These agents are used with or without ultraviolet light exposure. Effective programs can be designed for patients who do not have access to a therapeutic light source and for patients who have limited disease. Without light, tar is moderately effective, but persistent use of calcipotriene or tazarotene can clear the disease and offers the patient substantial remission periods. Topical steroids work quickly, but total eradication of the plaques is difficult to accomplish; remission times are short, and the creams become less effective with continued use.

Patients with psoriasis covering more than 5% of the body need special treatment programs (see Table 8.1 ).

Determining Degree of Inflammation.

The most common form of psoriasis is the localized chronic plaque disease involving the skin and scalp. It must be determined whether the plaque is inflamed before instituting therapy ( Fig. 8.36 ). Red, sore plaques can be irritated by tar, calcipotriene, and anthralin. Irritation can induce further activity. Inflammation should be suppressed with topical steroids and/or antibiotics before initiation of other treatments.

Erythrodermic psoriasis. This highly inflamed form of psoriasis responds well to acitretin as monotherapy.

Determining the End of Treatment.

The plaque is effectively treated when induration has disappeared. Residual erythema, hypopigmentation, or brown hyperpigmentation is common when the plaque clears; patients frequently mistake the residual color for disease and continue treatment. If the plaque cannot be felt by drawing the finger over the skin surface, treatment may be stopped. Patients should apply an emollient to the previously treated areas to keep the skin healthy and prevent recurrence.

Duration of Remission.

Among topical monotherapy, anthralin and tazarotene induce longer remissions than calcipotriene and corticosteroids; among systemic agents, longer remissions occur with acitretin than CS or MTX, but compared with the remission rate of phototherapeutic modalities, the remission rates are much less ( Fig. 8.37 ). Traditional Goeckerman therapy, conducted in a day treatment setting, is more likely to induce prolonged remissions than simple UVB phototherapy, “home Goeckerman therapy” using liquor carbonis detergens (LCD), or heliotherapy. PUVA phototherapy also induces prolonged remissions.

Psoriatic plaques under treatment with anthralin. As with all forms of treatment, plaques first clear in the center.

Some treatments are better suited for rapid clearing; others are better suited to be maintenance treatment. The optimum management involves the sequential use of therapeutic agents involving three steps, namely: the clearing phase, the transitional phase, and the maintenance phase.

Topical Therapy

Systemic Therapy

Topical treatment has its limits. Many patients do not respond to the most vigorous topical programs, or the disease may be so extensive that topical treatment is not practical.

Moderate to severe psoriasis, variably defined as patients with 5% or more involvement of body surface area or patients unresponsive to topical therapy, can be treated with several modalities including phototherapy, retinoids, MTX, or biologic agents (see Table 8.1 ).

A number of systemic drugs are available, some of which have potentially serious side effects. Methotrexate is highly effective, relatively safe, and well tolerated, but the need for periodic liver biopsies discourages some patients and physicians. Acitretin is used as a monotherapy for plaque, pustular, and erythrodermic forms of psoriasis. Acitretin may cause dry skin, alterations in triglycerides, and muscle soreness. Cyclosporine is rapidly effective, but long-term use may be associated with loss of kidney function. Biologic drugs are safe and effective for moderate to severe psoriasis.

Methotrexate

Indications and Use.

Methotrexate has been used for more than 40 years to treat severe psoriasis and is particularly effective in controlling erythrodermic and generalized pustular psoriasis ( Boxes 8.2 to 8.7 , Tables 8.13 and 8.14 ). It induces remissions in the majority of treated patients and maintains remissions for long periods with continued therapy. MTX is also effective for PsA. It is relatively safe and well tolerated. Methotrexate is used alone or in combination with biologics. Safe use of MTX requires appropriate monitoring. Awareness of the risk factors for hematologic toxicity, primarily decreased renal function, will significantly reduce this side effect. Awareness of the risks for hepatic toxicity is crucial. Patients without hepatic risk factors may not require routine liver biopsies. Folic acid supplementation is recommended to increase the safety and decrease the potential side effects.

TABLE 8.14

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