The skin in psoriasis: assessment and challenges V. Oji, T.A. Luger

Department of Dermatology, ABSTRACT tologist, who first diagnoses the skin University Hospital Münster, Germany. The coexistence of psoriasis arthritis disease. Hence, both specialties play an Vinzenz Oji, MD (PsA) and psoriasis vulgaris in about important role in early disease detec- Thomas A. Luger, MD, Prof. 20% of patients with psoriasis leads to tion and determining the course regard- Please address correspondence to: a need for rheumatologic-dermatologic ing further treatments of PsA as well as Vinzenz Oji, MD, team work. We summarise the role of psoriasis. Department of Dermatology, dermatologists in assessment of the skin This paper refers to the tasks of der- University Hospital Münster in psoriasis. Von-Esmarch Straβe 58, matologists in assessment of the skin 48149 Münster, Germany. Chronic plaque psoriasis must be dif- in a patient with psoriasis and/or PsA. E-mail: [email protected] ferentiated from other subtypes such as Clinically challenging aspects will be Received and accepted on September 29, generalised pustular psoriasis (GPP) addressed to strengthen the collabora- 2015. or palmoplantar pustulosis (PPP). tion of dermatology, , as Clin Exp Rheumatol 2015; 33 (Suppl. 93): Therapeutic management is based on well as general medicine, to care for S14-S19. the evaluation of the disease severity. patients with psoriasis. First of all the © Copyright Clinical and Quantitative scoring of skin severity diagnosis of psoriasis must be identi- Experimental Rheumatology 2015. includes calculation of the Psoriasis fied. The differential diagnoses includes Area and Severity Index (PASI), body eczema or mycosis fungoides, and the Key words: plaque psoriasis, surface area (BSA) as well as the Der- distinct type of skin psoriasis should generalised pustular psoriasis, matology Life Quality Index (DLQI). be defined, i.e. psoriasis vulgaris (PV) palmoplantar pustulosis, PASI, These scoring systems do not replace manifesting as chronic plaque psoriasis DLQI, BSA, PGA, comorbidity the traditional dermatologic medical has to be distinguished from generalised history and physical examination of the pustular psoriasis (GPP), palmoplantar patient. The skin should be examined pustulosis (PPP), or acrodermatitis con- for additional skin diseases; moreover, tinua suppurativa (6, 7). We focus on patients should be monitored for co- PV and summarise the specific clinical morbidity, most importantly PsA and tools which are commonly used for the cardiovascular comorbidity. assessment of disease severity, and de- scribe some challenges that may occur. Introduction Assessment of the skin of patients with Psoriasis is a chronic inflammatory PV or PsA is a component of a com- skin disease affecting about 2% of the plete dermatological examination: Caucasian population (1). About 20% thoroughly performed it takes into ac- of the patients have count important individual aspects of (PsA) (2, 3). Many patients with pso- the skin status such as the number of riasis are not aware of their PsA; and melanocytic nevi or the tendency to the prevalence of undiagnosed PsA is skin dryness and atopy (Table I). Im- still high as has been shown in a recent portantly, patients have to be moni- systematic meta-analysis. Accordingly, tored for skin tumours or precancerous up to 15.5% of patients with psoriasis lesions such as basal cell carcinoma, had undiagnosed PsA (4). Dermatolo- squamous cell carcinoma or actinic gists usually are the doctors consulted keratoses, respectively, taking into ac- in cases of new-onset psoriasis (5). In count the often increased cumulative collaboration with rheumatologists risk of carcinogenic sun exposure, UV they should screen their patients with light treatment and/or immunosuppres- psoriasis for PsA, as PsA is a progres- sive therapies (8). sive disease, and a subgroup of patients develops progressive damage and loss Key features of skin psoriasis of function in the first few years of the Psoriasis vulgaris (PV) is diagnosed disease (4). On the other hand, in about by the characteristic psoriatic plaques 6 to 18% PsA may precede skin lesions consisting from salmon red sharply Competing interests: none declared. (3, 4). Then it usually is the rheuma- bordered macules covered with silvery

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Table I. Dermatological assessment of patients with psoriasis. teal cleft, groins, and retro-auricular ar- eas have not been examined. Involve- Definition of psoriasis type/s Concomitant skin disorders or history of these Plaque psoriasis (Psoriasis vulgaris) Infections ment of the lips is possible; involve- Palmoplantar pustulosis (PPP) Tumours ment of the mucous membrane would Acrodermatitis continua suppurativa Eczemas be extremely unusual (1, 9). However, Generalised pustular psoriasis (GPP) considering potential differential diag- ± Psoriasis arthritis (PsA) Vitiligo Predilection sites of the skin noses such as lichen planus or adverse Scalp (retroauricular) Urticaria reactions of systemic therapies (Fig. 2) Extensor sites Dermatitis herpetiformis Duhring inspection of the mouth should be per- Nails Cutaneous lupus erythematodes formed in all patients with psoriasis. Flexural / genitals (gluteal cleft) Scars (after tumour excision) General aspects of the skin Comorbidity / cardiovascular risk factors Nail psoriasis is extensively described Pigmentation type Body Mass Index (BMI) elsewhere in this supplement. In short, Number of nevi Hyperlipidaemia 15–50% of patients with psoriasis have Skin dryness Hypertension Mucous membrane (tonsils) Other diseases or history of these* nail changes. This figure increases to Teeth Rheumatologic / orthopaedic 85% in patients with psoriatic arthritis Conjunctivae Gastrointestinal / hepatic / renal (10). Nail pitting, oil spots and onych- Neurological / psychiatric olysis are highly diagnostic (11). Cancer / haemolymphatic Allergies Distinct subtypes of psoriasis *incl. screening for psychological distress, fatigue, smoking and alcohol consumption. Plaque psoriasis should be differenti- ated from other psoriasis forms, which scales. Knees, elbows, scalp and um- It presents with erythematous sharply are clinically distinct and have a differ- bilicus are commonly affected (Fig. 1). demarcated areas, typically without sil- ent genetic background (1, 9, 12). GPP Importantly, the diagnosis of inverse very scaling. Patients may not address is now regarded an autoinflammatory psoriasis, in which only the flexural symptoms of inverse psoriasis. Hence, skin diseases (DIRA/DITRA, etc.) (13). folds are affected, should not be missed. psoriasis cannot be excluded if the glu- It has a different, more rapid disease

Fig. 1. Clinical examples of distinct forms of psoriasis and special localisations of psoriasis vulgaris: severe chronic plaque psoriasis (PASI 21.6) (a), pal- moplantar pustulosis in a female patient with Sapho syndrome (b), generalised pustular psoriasis in a patient with IL36 receptor mutations (c), acrodermatitis continua suppurativa in a patient also suffering from psoriasis vulgaris (d), psoriasis capitis as most common location of psoriasis vulgaris (e), severe nail psoriasis (f), inverse psoriasis first misdiagnosed as mycosis g( ), isolated palmar psoriasis vulgaris (h), and psoriasis of the external ear canal and scalp (i).

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Fig. 2. Clinical examples of concomitant skin diseases in patients with psoriasis: squamous cell carcinoma in a patient, who regularly used sun bathing as self-therapy (a), basal cell carcinoma origination from a scare in a patient suffering from psoriasis arthritis treated with (b), mild lichen planus of the gingiva in a patient under biologics (c), multiple actinic keratoses in a patient with plaque psoriasis, who had received a high cumulative dosage of UVB light therapy (d), palmar pustulosis (e) and mild exanthema (f) in a female with nail psoriasis and psoriasis arthritis, who had received a TNF-alpha blocker. course characterised by flares, continu- defined by pustular eruptions, initially Plaque psoriasis: ous development of pustules, often with affecting the tip of the fingers and nails, assessment of disease severity fever (1, 6, 13). PPP is a very chronic often affecting the bony structures of In psoriasis initiation of therapy and disease of the feet and/or hands char- the distal phalanxes (1, 6) (Fig. 1). Co- monitoring of the therapeutic effective- acterised by persisting sterile pustules existence of different types of psoriasis ness are based largely on evaluation of with or without hyperkeratotic derma- may occur. PsA can be associated with the disease severity. Therefore, scoring titis (1, 14). each of them, but frequency and type of skin severity is a necessity in psoria- Several reports document that biologic of the arthritic component might differ, sis care. More than 44 different scoring therapies with TNF-antagonists may e.g. PPP may be more often associated systems were used in 171 randomised cause de novo occurrence or exacer- with SAPHO syndromic sternoclavicu- clinical trials of psoriasis therapies bation of this form of psoriasis (15). lar and sternomanubrial tenderness and between 1997 and 2000 (17). Com- Acrodermatitis continua suppurativa is pain (16). mon tools to score psoriasis include determination of the area involved Table II. Examples of relevant clinical severity scores for plaque psoriasis and their items. in relation to the whole body surface (Body Surface Area, BSA) (18, 19), Erythema Desqua- Infiltration BSA Psychosocial History of Calculated the Physician Global Assessment (19) mation impact the illness by and and the Psoriasis Area and Severity In- treatment dex (PASI), which was constructed by Frederiksson and Pettersson (19, 20) in PASI + + + + - - Physician order to assess the severity of PV. The BSA - - - + - - Physician PASI score includes a number of well- PGA + + + - - - Physician defined dermatological parameters, LS ⁄ PGA + + + + Physician e.g. skin redness and infiltration cor- SPI + + + + + + Physician responding to the inflammatory com- saSPI + + + + + + Patient ponent of the disease, and allows for proSPI + + + + + + Physician scoring of skin area involvement (see SAPASI + + + + - - Patient below). PASI: Psoriasis Area and Severity Index; BSA: Body Surface Area; PGA: Physicians Global Assessment; The Salford Psoriasis Index (SPI) is LS: Laatice System Physician’s Global Assessment; SPI: Salford Psoriasis Index Simplified Psoriasis derived from combining a converted Index; saSPI: self-assessment Simplified Psoriasis Index; proSPI: professional Simplified Psoriasis -In dex; SAPASI: Self Administered Psoriasis Area Severity Index. [adapted from Puzenat et al. 2012 (24)]. figure of the PASI, a second score in- dicating psychosocial disability, and a

S-16 Dermatological assessment of psoriasis / V. Oji & T.A. Luger third score based on historical informa- tion (21). Chularojanamontri et al. re- cently published a modified version of the SPI renamed to Simplified Psoriasis Index (22). However, no single instru- ment captures all dimensions of psoria- sis severity (23). Puzena et al. selected six relevant clinical severity scores (PASI, BSA, PGA, LS-PGA, SPI and SAPASI) (Table II) and compared their methodological validations and quality (24). They conclude that the PASI is the most thoroughly validated score and can be recommended for quantitative evaluation of clinical severity of pso- riasis. This conclusion is in agreement with the recommendations of current consensus guidelines for the manage- ment of psoriasis (8, 25).

The Psoriasis Area and Severity Index (PASI): everyday clinical practice For calculation of the PASI four main body areas are assessed: the head (h), the trunk (t), the upper extremities (u) and the lower extremities (l), corre- sponding to 10, 20, 30 and 40% of the total body area, respectively (Fig. 3). The area of psoriatic involvement of Fig. 3. Assessment of disease severity in psoriasis vulgaris: PASI scheme and calculation; the neck these four main areas (Ah, At, Au and is assessed together with the heat; buttocks are assessed with the legs (a). Example of a patient with b Al) is given a numerical value: 0 = no plaque psoriasis (arms and trunk); the total sum of the PASI of this patient was 15.3 ( ). involvement; 1 = <10%; 2 = 10<30%; 3 = 30<50; 4 = 50<70%; 5 = 70<90%, index can be used in everyday clinical General aspects of skin assessment and 6 = 90–100%. To evaluate the se- practice to manage patients with plaque General aspects of skin examination verity of the psoriatic lesions three tar- psoriasis, in particular, if a systemic often influence the treatment options get symptoms, namely erythema (E), treatment is considered (23, 25). How- and strategies, e.g. skin dryness may infiltration (I), and desquamation (D) ever, the PASI is not applicable for GPP increase pruritic symptoms of psoria- are assessed according to a scale 0–4, or PPP and does not specifically con- sis, so that systemic therapy should be where 0 means a complete lack of cu- sider the severity of nail involvement combined with regular moisturising. taneous involvement and 4 represents (11, 26). For first-line treatment of plaque pso- the severest possible involvement. The riasis, a high number of melanocytic severity rating for the three main tar- Scoring of nail psoriasis nevi may be regarded a contraindica- get symptoms is multiplied with the Nail psoriasis has a substantial impact tion for UV treatment. Moreover, skin numerical value of the areas involved on patients‘ quality of life (11, 26). tumours or a history of these may rep- and with the various percentages of the Several scoring systems have been pro- resent a relative contraindication for four body areas. These values are then posed to assess nail psoriasis severity, immunosuppressive therapies. Hence, added to obtain the PASI. The formula e.g. the NAPSI (Nail Psoriasis Severity dermatological monitoring is neces- can be written as follows (20): Index) has often been used in clinical sary before and during treatment (1, 8). studies (27) (see elsewhere in this sup- Patients with PV or PsA under treat- PASI = 0.1 x Ah x (Eh + Ih + Dh) + 0.3 x plement). For therapy monitoring of ment with biologic agents should be At x (Et + It + Dt) + 0.2 x Au x (Eu + Iu + nail psoriasis we recommend regular observed for the development of other Du) + 0.4 x Al x (El + Il + Dl) photo-documentation and evaluation immune-mediated skin diseases, e.g. The index varies in steps of 0.1 units of the dynamic Physician Global As- lichen planus, vitiligo, alopecia areata, from 0.0 to 72.0 (20); and there are sessment (dynamic PGA) of the nails, and of course certain drug eruptions multiple online tools for PASI training e.g. as a 5-point ordinal rating ranging should be seen by the dermatologist and computing (Table III). As such, the from “clear” to “very severe” (11, 19). (Table I, Fig. 2).

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Dermatologic evaluation includes Table III. Internet resources for the assessment and management of skin psoriasis*. assessment of health-related quality PASI of life and comorbidity http://www.pasitraining.com/calculator/step_1.php The assessment of psoriasis severity http://pasi.corti.li should take into account its burden on http://www.dermnetnz.org/scaly/pasi.html DLQI health-related quality of life (HR-QoL) http://www.cardiff.ac.uk/dermatology/quality-of-life (23). As mentioned above, the PASI is http://www.pasitraining.com/dlqi insufficient to assess functional disabil- Dermatological guidelines for the management of patients with psoriasis ity secondary to specific localisations of http://www.ncbi.nlm.nih.gov/pubmedhealth http://www.awmf.org/leitlinien skin lesions, e.g. on the face, hands or nails. Moreover, patients with psoriasis *last accessed 6-9-2015. often suffer from pruritus, cutaneous pain, burning sensations, bleeding, and/ tologic diseases, neoplasm or allergy manifestations may have a substantial or social-life impairment (23, 25). In (Table I). From epidemiologic studies impact on the dynamic or static Phy- clinical practice evaluation of all these it has been well established that severe sician Global Assessment (PGA) (19), symptoms might be perceived as cum- psoriasis is associated significantly which can alter the classification of bersome; however, validated scales as- with a moderate increase of risk for dia- mild disease to moderate-to-severe dis- sessing the burden of plaque psoriasis betes and obesity (5, 33). A recent pop- ease (23): on HR-QoL are the Dermatology Life ulation-based Swedish register study • involvement of visible areas Quality Index (DLQI) (28), the Short- showed that mild and severe psoriasis • involvement of major parts of the Form 36 (SF-36) and the Skindex 29 are associated with increased mortality scalp and Skindex 17 (23) that may be com- rates as patients with severe psoriasis • involvement of genitals pleted by the patients in 3–15 minutes. die on average 2.6 years younger than • involvement of palms and/or soles The DLQI consists of 10 questions con- age-, sex-, and residency-matched con- • or onychodystrophy of cerning symptoms and feelings, daily trol subjects. The increases in all-cause at least two fingernails activities, leisure, work, and school, mortality observed were largely attrib- • pruritus leading to scratching personal relationships and treatment. uted acutely to increased cardiovascu- • presence of single recalcitrant All questions relate “to the last week”, lar mortality (34). For this reason, new plaques and the score ranges from 0 (no impair- dermatological guidelines do not only ment of life quality) to 30 (maximum refer to the skin, but also recommend to Definition of treatment effectiveness impairment). The tool has been trans- determine the Body Mass Index (BMI) The reduction in PASI of ≥75% (Δ lated into at least 21 different languag- (upper limit: 30 kg⁄m2) and/or waist cir- PASI ≥75) has been considered to in- es. There is a children’s version of the cumference (upper limit: 94 cm in men, dicate treatment success after an antip- DLQI (29), the Children’s Dermatology 80 cm in women) in patients with mod- soriatic treatment has been initiated (8, Life Quality Index (CDLQI), and a text erate to severe psoriasis (23). 25). Clinical studies on the effectiveness and cartoon version of this has been de- of systemic therapy in plaque psoriasis scribed (30) (Table III). Combination of skin assessment may note that a certain proportion of A definition of the different scores of tools and therapy algorithm patients experienced a 75% reduction the DLQI and their impact on patients’ A recent consensus program for the in their PASI scores over a 3-months life allows a reliable grading of the im- treatment of plaque psoriasis defined treatment period and report this as a pact on quality of life (31). By using a number of important items related to percentage of people achieving “PASI this definition in psoriasis, a DLQI <5 psoriasis assessment and therapy (8, 75”. With the development of new and would indicate only mild impact on an 25). Current guidelines distinguish be- highly effective biologic agents, treat- individual patients’ quality of life (23, tween “mild” and “moderate to severe” ment goals are being newly defined as 25, 32). psoriasis, but, as discussed above, a Δ PASI 90 or even Δ PASI 100 (35). single assessment tool for disease se- In patients who have a Δ PASI of ≥50% Comorbidity verity is not sufficient to reflect all but <75%, the impact of the disease on From the dermatological perspective, clinical situation. For plaque psoriasis quality of life, which can be estimated PsA is the most important comorbidity; the following definitions have been from the DLQI, may be of value to de- and of course its diagnosis and treat- consented (25, 32): cide either to continue or modify a treat- ment should not be delayed. The initial ment regimen. Therefore, it is advisable Definition of “mild” plaque psoriasis dermatological assessment of patients to assess the DLQI in patients with skin BSA ≤10 and PASI ≤10 and DLQI ≤10 with psoriasis or PsA should include a psoriasis before initiation of a systemic concise query, whether there is a histo- Definition of “moderate-to-severe” treatment and during the follow-up vis- ry of specific gastrointestinal, hepatic, plaque psoriasis its. For nail psoriasis, the DLQI may be renal, endocrinologic, neurologic, psy- BSA >10 and PASI >10 and DLQI >10 used in combination with the dynamic chiatric, orthopaedic or other rheuma- The presence of the following disease PGA of the nails (11).

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Conclusion ysis. J Am Acad Dermatol 2015; 73: 242-8. 21. KIRBY B, FORTUNE DG, BHUSHAN M, CHAL- Assessment of the skin in patients with 5. RADTKE MA, MROWIETZ U, FEUERHAHN MERS RJ, GRIFFITHS CE: The Salford Pso- J et al.: Early detection of comorbidity in riasis Index: an holistic measure of psoriasis psoriasis is based on quantitative scor- psoriasis: recommendations of the National severity. Br J Dermatol 2000; 142: 728-32. ing tools. The Psoriasis Area and Sever- Conference on Healthcare in Psoriasis. 22. CHULAROJANAMONTRI L, GRIFFITHS CE, ity Index (PASI) is the best validated J Dtsch Dermatol Ges 2015; 13: 674-90. CHALMERS RJ: The Simplified Psoriasis In- score for defining disease severity in 6. RAYCHAUDHURI SK, MAVERAKIS E, RAY- dex (SPI): a practical tool for assessing pso- CHAUDHURI SP: Diagnosis and classification riasis. J Invest Dermatol 2013; 133: 1956-62. psoriasis vulgaris (23). New treatment of psoriasis. Autoimmun Rev 2014; 13: 490-5. 23. 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