Psoriasis

01Pathophysiology

Psoriasis is a chronic, immune-mediated inflammatory disease with a strong genetic predisposition. The strongest genetic association is with HLA-Cw6, a class I MHC molecule. Having a first-degree relative with psoriasis raises risk substantially.

The central driver is dysregulation of the adaptive immune system, particularly the Th1 and Th17 lymphocyte pathways. Dendritic cells in the skin become activated by various triggers (infection, trauma, stress, drugs such as lithium or beta-blockers) and migrate to regional lymph nodes, where they present antigens to naive T cells. This activates T cells that produce a cascade of pro-inflammatory cytokines: TNF-alpha, IL-17, IL-22, and IL-23. These cytokines act on keratinocytes and stimulate them to proliferate at a dramatically accelerated rate.

In normal skin, the keratinocyte turnover cycle takes approximately 28 to 30 days. In psoriatic skin, this is compressed to roughly 3 to 5 days. The keratinocytes do not have time to mature properly, which produces the characteristic parakeratosis (retention of nuclei in the stratum corneum). The silvery-white scale seen clinically is the gross manifestation of this thick, immature keratinized layer.

The inflammatory infiltrate also causes dilation of dermal capillaries and neovascularization in the dermal papillae. These dilated, tortuous vessels sit very close to the surface because the suprapapillary plate (the epidermis overlying the papillae) is thinned. This explains the Auspitz sign: when you peel off the adherent silvery scale, you expose these superficial capillaries and trigger pinpoint bleeding.

Munro microabscesses, collections of neutrophils within the parakeratotic stratum corneum, are the hallmark histological finding. Neutrophils are recruited by IL-8 and other chemokines released by activated keratinocytes.

The Koebner phenomenon (isomorphic response) occurs because the immune priming in psoriasis is systemic, not localized. Any trauma to the skin recruits immune cells and cytokines to the site of injury, triggering a new psoriatic plaque at that location. This is why vignettes may describe lesions appearing at a surgical scar or site of a scratch.

02Classification and Clinical Manifestation

03Diagnostic Workup

Psoriasis is overwhelmingly a clinical diagnosis. The combination of well-demarcated erythematous plaques with adherent silvery scale on extensor surfaces, positive Auspitz sign, and the classic distribution pattern (elbows, knees, scalp, lumbosacral region, nails) is usually sufficient.

A skin biopsy becomes necessary when the presentation is atypical, when you need to differentiate from mimics such as cutaneous T-cell lymphoma (mycosis fungoides), or when the patient fails initial therapy. The histological pattern is highly characteristic: regular acanthosis with elongation of rete ridges (sometimes described as a "test-tube" pattern), thinning of the suprapapillary plate, parakeratosis, and Munro microabscesses. These findings together are essentially pathognomonic.

For guttate psoriasis, always consider checking an ASO titer or obtaining a throat culture. The classic vignette describes a child or adolescent who develops a widespread, droplet-like rash 2 to 3 weeks after a sore throat. Confirming recent streptococcal infection supports the diagnosis and may guide treatment with antibiotics if the infection is still active.

When psoriatic arthritis is on the differential, the key lab finding is seronegativity for RF and anti-CCP. This distinguishes it from rheumatoid arthritis. Imaging reveals characteristic changes at the DIP joints, including the pencil-in-cup deformity, periostitis, and new bone formation. The pattern of joint involvement (DIP predominance, dactylitis, enthesitis, asymmetry) further distinguishes it from RA.

Do not forget comorbidity screening. Psoriasis carries elevated risk for cardiovascular disease, metabolic syndrome, non-alcoholic fatty liver disease, and depression. Vignettes may test your awareness of these associations.

04Management and Treatment

Mild disease is treated with topical agents. The backbone of topical therapy is corticosteroids. For body and extremity plaques, use medium-to-high potency steroids (e.g., betamethasone dipropionate 0.05%, clobetasol propionate 0.05%) applied once to twice daily for 2 to 4 weeks, then taper. For the face, genitals, and intertriginous areas, use low-potency steroids (hydrocortisone 1%) or preferably topical calcineurin inhibitors (tacrolimus 0.1% ointment) to avoid steroid-induced skin atrophy in thin-skinned areas.

Vitamin D analogs (calcipotriol/calcipotriene 0.005%) are frequently combined with topical steroids. They work by inhibiting keratinocyte proliferation and promoting differentiation. The combination product (calcipotriol + betamethasone dipropionate) is superior to either agent alone and is a commonly tested first-line choice.

When topical therapy is inadequate, the next step is phototherapy. Narrowband UVB (NB-UVB) is the preferred modality, typically administered 3 times per week for 12 to 24 weeks. It works by inducing T-cell apoptosis in the skin. PUVA (oral psoralen plus UVA light) is reserved for refractory cases because of its higher long-term risk of squamous cell carcinoma and cataracts.

Systemic therapy is indicated for moderate-to-severe disease or when phototherapy is impractical.

Methotrexate is often the first-line systemic agent. It is given at 7.5 to 25 mg orally or subcutaneously once weekly, supplemented with folic acid 1 mg daily (except on the methotrexate day) to reduce mucosal and hematologic side effects. Monitoring requires a baseline CBC, liver function tests (LFTs), and renal function, repeated every 1 to 3 months. The major long-term concern is hepatotoxicity and hepatic fibrosis. Methotrexate is absolutely contraindicated in pregnancy (FDA Category X; teratogenic) and in patients with significant liver disease or active infection.

Cyclosporine (3 to 5 mg/kg/day divided twice daily) provides rapid disease control and is useful for acute flares or as a bridge to slower-acting therapies. Its use is limited to 1 to 2 years due to the risk of nephrotoxicity and hypertension. Monitor blood pressure, serum creatinine, and potassium regularly.

Acitretin (25 to 50 mg daily) is an oral retinoid particularly useful for pustular and erythrodermic psoriasis. It is teratogenic with an exceptionally long washout period: women must avoid pregnancy for 3 years after discontinuation (because acitretin can be converted to etretinate in the presence of alcohol, and etretinate has a half-life of 120 days stored in adipose tissue).

Biologic agents represent the most targeted therapies and are reserved for moderate-to-severe disease failing conventional systemic treatment.

• TNF-alpha inhibitors: adalimumab (40 mg subcutaneously every 2 weeks), etanercept, infliximab. Screen for latent tuberculosis (PPD or interferon-gamma release assay) and hepatitis B before initiation.

• IL-17 inhibitors: secukinumab (300 mg subcutaneously, loading dose at weeks 0, 1, 2, 3, 4, then monthly), ixekizumab.

• IL-12/23 inhibitor: ustekinumab (45 mg for patients under 100 kg, 90 mg for patients over 100 kg, subcutaneously at weeks 0, 4, then every 12 weeks).

• IL-23 inhibitors: guselkumab, risankizumab (among the most effective agents, with dosing every 8 to 12 weeks after loading).

Apremilast (30 mg orally twice daily after a titration week) is a PDE4 inhibitor that offers oral convenience without immunosuppression-level monitoring but has modest efficacy compared to biologics.

Critical contraindications to remember: Never abruptly withdraw systemic corticosteroids in a psoriasis patient, as this can precipitate a pustular or erythrodermic flare. This is a classic exam trap.

05Differential Diagnosis and Distractors

06Traps and High-Yield Pearls

The most common way students lose points on psoriasis questions is by confusing flexural and extensor predilection. Psoriasis favors extensors (elbows, knees); eczema favors flexors. When a vignette describes a well-demarcated, silvery-scaled plaque on the elbow of an adult, psoriasis is the answer. When it describes an ill-defined, oozing, excoriated patch in the antecubital fossa of a child with a history of asthma, it is eczema. This extensor-versus-flexor distinction is the single most tested discriminator.

The second major trap is the guttate psoriasis vignette. Test-writers will describe a teenager who presents with a sudden eruption of small, drop-like, scaly papules on the trunk 2 to 3 weeks after a sore throat. Students who do not link the preceding streptococcal pharyngitis to the rash will miss this diagnosis. Always look for a recent upper respiratory infection in a young patient with new-onset widespread small papules.

Third, be alert for the steroid withdrawal trap. A vignette may describe a psoriasis patient who was placed on systemic corticosteroids (perhaps for another condition) and then had them stopped abruptly, triggering a catastrophic pustular or erythrodermic flare. The core competency here is recognizing that systemic corticosteroids should never be used as long-term therapy for psoriasis and should never be withdrawn suddenly.

Fourth, remember the nail and joint connection. When a vignette describes nail pitting plus asymmetric DIP joint swelling with a negative RF, the answer is psoriatic arthritis. The seronegative arthritis pattern (RF-negative, anti-CCP-negative) with DIP involvement, dactylitis, or enthesitis points directly to psoriatic arthritis over rheumatoid arthritis. Pencil-in-cup deformity on X-ray seals the diagnosis.

Finally, do not overlook the comorbidity angle. A question may present a patient with known psoriasis and then ask about cardiovascular risk stratification or metabolic syndrome screening. Psoriasis is an independent risk factor for cardiovascular events, and this association is increasingly tested.

The core competency being assessed across psoriasis questions is your ability to recognize the classic clinical morphology (well-demarcated, silvery, extensor plaques), connect subtypes to their triggers (strep for guttate, steroid withdrawal for pustular/erythrodermic), sequence management correctly (topical before phototherapy before systemic before biologic), and identify the seronegative arthritis pattern when joints are involved.