Disease initiation of complex diseases, such as psoriasis, takes place in genetically predisposed individuals in which a dysregulated immune response occurs following exposure to certain environmental triggers. Although mechanistic associations linking distinct environmental factors with specific genetic determinants and dysregulated immune processes are still scarce, critical determinants of this pathogenic interplay have been identified
Psoriasis is a dynamic disease; morphological changes accompany the evolution of a newly formed lesion into an advanced plaque that can slowly enlarge (active lesions, sharing most of the histological features of newly formed lesions) or remain static (stable lesions, retaining the morphology of the advanced stage).
Early stages:In the early stages of a newly developing plaque, the first changes occur in the uppermost layer of the dermis, the papillary dermis.
- Blood vessel changes:
- Dilated and tortuous blood vessels
- Squirting papilla: Lymphocytes & neutrophils emerging from their lumen)
- Aberrant keratinocyte (KC) proliferation and migration:
- Epidermal thickening
- Incomplete terminal differentiation with initial loss of “stratum granulosum”
- Parakeratosis: Retention of nucleus by corneocytes)
Advanced stage:Fully flagged psoriasis hyperplasia is present. Lesions can spontaneously resolve, although rarely.
- Acanthosis (thickening of stratum spinosum)
- Papillomatosis (elongation of rete ridges extending downward between dermal papillae)
- Confluent Parakeratosis
- Lymphocytes (mainly CD8+ T cells) interspersed between KCs
- Munro microabscesses: Neutrophils accumulate into the parakeratotic scales
- Auspitz sign: Dilated blood vessels extend high into papillae, accounting for pinpoint bleeding when a scale is removed
- Dermis heavily infiltrated by T cells and dendritic cells (DC)
Resolving lesions after therapy:
- Woronoff’s ring: Distinctive rim of blanching predictive of clearing
- Orthokeratosis: Thickening of the stratum corneum without parakeratosis
- Restoration of stratum granulosum
Psoriasis vulgaris aka. chronic stationary psoriasis or plaque-like psoriasisPlaque-type psoriasis, occurring in of affected patients, is the most common form of psoriasis and is characterized by oval or irregularly shaped, red, sharply demarcated, raised plaques covered by silvery scales
- M/C form of psoriasis
Guttate psoriasis:Guttate psoriasis, from the Latin “gutta” for tear drop, is characterized by multiple small scaly plaques usually occurring around the trunk and upper arms and thighs. The rash has often sudden onset, usually within 2–4 wk after a bacterial infection of the upper ways, notably streptococcal pharyngitis in children and young adults, and is therefore associated with type I psoriasis. Guttate psoriasis can either completely clear spontaneously or following topical treatment, become chronic, or worsen into the plaque type.
Generalized Pustular Psoriasis (GPP) aka von Zumbush psoriasisGPP is a rare but potentially life-threatening disease characterized by episodic, widespread skin and systemic inflammation. Acute attacks often occur during pregnancy and may be triggered by infection, exposure to or withdrawal from drugs. GPP can be frequently associated with plaque-type psoriasis and/or palmoplantar pustular psoriasis.
- Spongiform pustules of Kogoj: Prominent aggregates of neutrophils infiltrating the stratum spinosum
- Sterile cutaneous pustules
- Skin manifestations are associated with marked systemic features: high fever, fatigue, and neutrophils leukocytosis
Erythrodermic psoriasis:One of the rarest forms of psoriasis (1%–2.25%), represents the most severe phenotype; it carries substantial morbidity and can be potentially life threatening. GPP may revert to erythrodermic psoriasis when pustule formation stops. Both administration and abrupt withdrawals of systemic corticosteroids or methotrexate, sunburn, and emotional stress have been suggested as possible triggering factors
- Diffuse erythema, with/without scaling, involving >75% of the skin surface. If present, scales are only superficial and differ from the adherent scales of plaque psoriasis.
- Systemic manifestations:
- Hypothermia and limb edema (because of the generalized vasodilation underlying the erythema)
- Myalgia, fatigue, and fever
Inverse psoriasis (flexural psoriasis)Inverse psoriasis, also known as intertriginous or flexural psoriasis , affects 3–7% of psoriasis patients. It involves the skinfolds, including the axillae, genital regions, and inframammary and inguinal creases. The face can also be involved. These lesions are less likely to be scaly given the high moisture in these areas and mainly present as shiny, erythematous plaques. Fissuring and superimposed bacterial or fungal infections may occur. Histologically, there is no difference between inverse and plaque psoriasis, and thus the two are differentiated on clinical presentation alone. Notably, psoriasis patients with palmar involvement are approximately five times more likely to have inverse psoriasis than classic plaque psoriasis
Nail changes:Nail changes can occur in any type of psoriasis. Among patients with psoriasis, fingernail changes occur in 50% of patients and toenail changes occur in 35% of patients. Nail changes are common in psoriatic arthritis patients, occurring in up to 90% of cases. Many of the structures within the nail unit can be affected, resulting in a broad range of clinical presentations.
- “Oil drop” spots
- Splinter hemorrhages
- Subungual hyperkeratosis
- Grattage test: Scraping of the surface of a psoriasis plaque reveals loosely attached scales and reveal a shiny surface peppered with fine bleeding point
- Auspitz test: Appearance of punctate bleeding spots when psoriasis scales are scraped off
- Köbner phenomenon: Appearance of skin lesions on lines of trauma
Psoriasis Area and Severity Index (PASI):Most widely used measurement tool which assesses the severity of the condition and allows to evaluate the treatment efficiency.
- Seborrhoeic dermatitis
- Pityriasis rosea
- Mycosis fungoides (a form of cutaneous T-cell lymphoma)
- Secondary syphilis
There is no definitive cure for psoriasis, and available treatment is only to decrease disease activity and improve symptoms.
Topical treatments:Used in mild-to-moderate psoriasis
- Topical corticosteroids: Reduces inflammation; Maintainance must be done or it may cause local skin atrophy
- Dithranol + Coal tar (Traditional treatment): Inhibit proliferation
- Vitamin D agonist (Calcipotriol): Reduces epidermal proliferation
Phototherapy:Reserved to moderate-to-severe cases. Guttate psoriasis has been known to respond best to phototherapy.
- PUVA therapy: Psoralen + UV light (UVA)/NBUVB (Narrowband UVB light; 311-313nm)
- NBUVB is equally effective without the side effects of psoralen like gastrointestinal upset, cataract formation, and carcinogenic effect. It can safely be given to children, pregnant and lactating females and even elderly.
Systemic therapies:Used in extensive cases, the involvement of nails and psoriatic arthritis. Routine blood, liver functions, and renal functions should be monitored in patients on systemic therapy.
- First line of treatment | Methotrexate (folic acid antagonist): Immunosuppressive, cytostatic, and anti-inflammatory activity
Biologics:Targeting key inflammatory mediators and currently representing an effective third-line therapy in moderate-to-severe psoriasis patients, unresponsive to nonbiologic systemic agents. Before starting any biological agent, the patient should be worked up for tuberculosis and hepatitis. There is a serious risk of infections in these patients and all precautions should be taken that the patient is not severely immunocompromised.
- Anti-TNF: Etanercept, Alefacept, Infliximab, Efalizumab