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psoriasis

Classification: - psoriasis vulgaris* (plaque psoriasis) most common - inverse psoriasis* - Guttate psoriasis* - erythrodermic psoriasis* (exfoliative psoriasis) 3% - pustular psoriasis* - sebopsoriasis - nail psoriasis * 5 psoriasis subtypes in [34] Etiology: 1) unknown 2) cold weather exacerbates, incidence higher in colder climates 3) hot weather & sunlight improve symptoms 4) stress & anxiety exacerbate psoriasis 5) trauma to the skin may lead to development of psoriasis in the affected area 6) pharmaceutical agents may exacerbate psoriasis: a) steroid withdrawal b) antimalarials c) lithium d) beta-blockers e) ACE inhibitors f) indomethacin, other NSAIDs? [3] g) TNF-alpha inhibitors h) interferons 7) infections can cause the onset or a flare of psoriasis a) Streptococcal infection (see guttate psoriasis) 1] especially children & adolescents 2] thought to be related to circulating factors 3] pharyngitis & tonsillitis 4] cellulitis b) HIV1 infection (new onset) - abrupt onset of psoriasis [3] - lesions psoriasis often resolve with increasing severity of immunodeficiency Epidemiology: 1) 1%-2% of population is affected - 2.2-3.15% in the U.S. - 1.3-2.6% in the U.K. [22] 2) males & females affected equally - prevalence in U.S. is 3.2% in women & 2.8% in men [47] 3) onset at any age, but 20's most common Pathology: (gross pathology) - generalized or localized pustular psoriasis, active stage - spongiform pustules of Kogoj are larger & are characteristic lesion - KRT17 may act as an autoantigen - granulocytes &/or monocytes play a major role [23] - neutrophils & monocytes aggravate & prolong psoriasis by releasing TNF-alpha [23] Microscopic Pathology: - psoriasis vulgaris, fully developed lesion - acanthosis with regular elongation of rete ridges which become club shaped - suprabasal mitotic figures - thinning of suprapapillary epidermis with occasional presence of small spongiform pustules - pallor of upper layers of epidermis - diminished to absent granular layer - confluent parakeratosis - Munro microabscesses* (collections of neutrophils in parakeratotic layer, found easily in earlier lesions, less so in long standing lesions) - spongiform pustules* of Kogoj (collections of neutrophils in spiny & granular layers, small, seen only in early or active stages) - elongation and edema of dermal papillae - mild inflammatory infiltrate in papillary & upper dermis, mostly lymphocytes - dilated tortuous capillaries * spongiform pustules of Kogoj and Munro microabscesses seen for diagnostic certainty) Mole= Genetics: 1) inhibition of RARRES2 expression 2) role for epidermal T-cell integrin alpha-1/beta-1, receptor for basement membrane collagen-4 [7] 3) overexpression of cornifelin, kallikrein-8 4) coexpression of KRT16 & KRT17 5) familial clusterings of psoriasis 6) defects in IL36RN are the cause of generalized pustular psoriasis [20] 7) susceptibility associated with HLA class 1 alpha Cw6 8) susceptibility associated with increased beta-defensin genomic copy number within beta-defensin gene cluster 9) susceptibility associated with deletion of the late cornified envelope LCE3B & LCE3C genes 10) susceptibility associated with polymorphisms in IL12B 11) mutations or gene deletions of junB [5] 12) high levels of ADAM17 expressed in the psoriasis, thus may olay a role in pathogenesis of psoriasis [49] 13) low levels of ADAM10 in psoriasis may be attributable to its regulatory role in keratinocyte differentiation and proliferation 14) other implicated genes [49] S100A7A, PLA2G4D, BPIL2, FNDC1, PSORS1C1, PSORS1C2, KPRP, RDHE2, SLC12A8, SLURP2, PSORS1C3, MICA, CASP14, IL20RA, IL20RB, S100A7, FABP5 Clinical manifestations: 1) symptoms: a) cosmetic b) scaling c) pruritus d) discomfort or pain e) heat loss f) arthralgia 2) signs: a) skin lesions - erythema - silvery micaceous scales - plaques with: - well-differentiated borders - symmetric distribution - Auspitz sign: removal of a plaque will result in a small amount of bleeding - papulosquamous pustules - may appear anywhere on the body - extensor surfaces (elbows, knees), scalp, ears, intertriginous folds, genitals, nails b) nails - nail-pitting, thickening - onycholysis (separation of nail plate from nail bed) - light brown discoloration of the nails (oil spots) - may be only manifestation of psoriasis [3] c) joints (also see psoriatic arthritis) - generally occurs after skin involvement, but may precede it - most often involves distal interphalangeal joints - usually asymmetric oligoarthritis - sacroiliitis - spondylitis - joint involvement occurs in 10-25% of patients with psoriasis - extent of skin disease does NOT correlate with severity of arthritis 3) generalized pustular psoriasis - life-threatening disease * images [33,34] Laboratory: - skin biopsy - suspected generalized pustular psoriasis - complete blood count (CBC): marked leukocytosis - serum C-reactive protein is elevated - flow cytometry (investigational) - circulating Th17 cells, Th22 cells, & Th1 cells are increased [32] Differential diagnosis: 1) eczema 2) tinea 3) candidiasis 4) drug eruptions 5) syphilis 6) seborrhea 7) Paget's disease 8) Bowen's disease 9) mycosis fungoides 10) lichen planus Complications: 1) pustular psoriasis: life threatening variant associated with glucocorticoid or cyclosporine withdrawal [3] 2) erythrodermic psoriasis: life-threatening exfoliative dermatitis associated with glucocorticoid or cyclosporine withdrawal [3] 3) increased risk of several associated systemic diseases: a) osteoporosis in men [10] b) metabolic syndrome [12] c) coronary artery disease & myocardial infarction [13] d) 10-fold increased risk of dilated cardiomyopathy [41] e) hypercholesterolemia (69%) [37] f) hypertension (47%) [11] g) diabetes mellitus type 2 (10%) [11,37] h) lymphoma [14] 3) increase risk of cancer [16,46] (18% overall) a) lymphoid neoplasms RR=1.8 b) pancreatic cancer RR=1.4 c) oral cancer RR~3 [46] d) esophageal cancer RR~2 e) squamous cell carcinoma RR~2 f) liver cancer RR=1.8 g) laryngeal cancer RR=1.8 h) bladder cancer [46] 4) increased risk of chronic renal failure [25] 5) cardiovascular disease is the most common cause of death in patients with severe psoriasis [3] 6) hyperuricemia & gout are comorbidities associated with psoriasis [3] 7) cognitive impairment [50' Management: === topical therapy: usually adequate === 1) topical glucocorticoids for localized disease a) first line therapy b) use less potent topical glucocorticoids first, especially in areas of occlusion or in skin folds [36] 2) occlusive dressing with or without topical steroids (Topiclude) 3) emollients 4) coal tar 5) anthralin 6) calcipotriene (Dovonex) vitamin D analog - calcipotriene/betamethsone (Dovobet) [21] 7) calcineurin inhibitors - tacrolimus (Protopic) or pimecrolimus (Elidel) [21] 8) tazarotene (Tarozac) gel 0.05% [21] === phototherapy === 1) reserve for involvement of > 10% of body surface or unresponsive to topical therapy [3] 2) recommended for Guttate psoriasis & chronic plaque psoriasis 3) narrow band UV-B has become standard for phototherapy [3] - home narrow band UV-B units for use without oral photosensitizer are almost as effective as PUVA [15] - UV-B light used in conjunction with tar or anthralin - add to topical glucocorticoid in pregnant women with worsening psoriasis not responding to topical glucocorticoid alone [52] 4) PUVA (oral psoralen & UV-A light) - increased risk of squamous cell carcinoma of the skin with PUVA 5) excimer laser vs pulsed-dye laser [6] 6) sunlight often leads to improvement of psoriasis === systemic therapy === 1) reserve for involvement of > 10% of body surface or unresponsive to topical therapy [3] 2) methotrexate: especially psoriatic arthritis 3) etretinate: a) may be used in conjunction with PUVA b) contraindicated in women who may bear children 4) acitretin [3] 5) cyclosporine [3] 6) hydroxyurea may deplete leukocytes [23] 7) glitazones (rosiglitazone & pioglitazone) off-label use [4] 8) etanercept (Enbrel) safe & effective [18] 9) adalimumab (Humira) safe & effective [18] 10) infliximab (Remicade) for severe refractory psoriasis [9] 11) IL-23 inhibitors - ustekinumab (Stelara) IL-12 & IL-23 inhibitor for severe refractory psoriasis; (first line) [39] - risankizumab IL-23 inhibitor - associated with better clinical responses than with ustekinumab [38] - >50% achieve clear skin in 1 year [43] - guselkumab (Tremfya) IL-23 inhibitor FDA approved - tildrakizumab-asmn [48] 12) IL17 inhibitors - brodalumab, an IL17A receptor monoclonal antibody (investigational) appears to be effective [19] - ixekizumab (Taltz) an IL17 monoclonal antibody - appears to be effective [19] - more effective at 12 weeks than ustekinumab [40] - caution with inflammatory bowel disease [39] - secukinumab (Cosentyx) an IL17A monoclonal antibody - caution with inflammatory bowel disease [39] - bimekizumab, an IL17A & IL17F inhibitor (investigational) effective in phase 2 study [42] 13) deucravacitinib (Sotyktu) FDA-approved for treatment of moderate to severe plaque psoriasis 14) tazarotene activates RARRES2 in psoriatic lesions 15) apremilast (Otezla) not recommended (NICE) === systemic therapy to avoid === 1) do NOT use systemic glucocorticoids [3] a) rebound worsening upon withdrawal b) possible conversion to pustular form with glucocorticoid withdrawal 2) psoriasis exacerbated by lithium carbonate, antimalarials, tetracyclines, beta-blockers, NSAIDs & ACE inhibitors === other considerations === 1) adsorptive granulocyte & monocyte apheresis is effective [23] 2) dietary measures to achieve weight reduction result in improvement of psoriasis & quality of life [31] 3) smoking cessation, smoking worsens psoriasis [3] 4) screening for cardiovascular disease [37] - cardiovascular disease common among patients with psoriasis [3] - reclassification of 1 in 3 patients with psoriasis to high cardiovascular risk [37] 5) referrals - generalized erythema & scaling involving most of the body (erythroderma) requires immediate referral to a dermatologist [3] Notes: - patient dissatisfaction with treatment common [24]

Interactions

disease interactions

Specific

erythrodermic psoriasis; exfoliative psoriasis inverse psoriasis nail psoriasis plaque psoriasis psoriasis vulgaris, Guttate-type psoriatic arthritis pustular psoriasis; impetigo herpetiformis, von Zumbusch's disease; acrodermatitis continua of Hallopeau rupioid psoriasis sebopsoriasis

General

autoimmune disease chronic skin disease (chronic dermatologic disorder, chronic dermatopathy, chronic dermatosis) psoriasiform dermatitis; psoriaform dermatitis

Database Correlations

OMIM correlations

References

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