What is psoriasis?

Psoriasis is a long-term disease condition where the immune system is overstimulated, resulting in rapid multiplication of skin cells. This causes the skin patches to look scaly and inflamed. These patches are frequently observed on the elbows, scalp, or knees. However, it can affect other parts of the body.¹ Psoriasis is often accompanied by other conditions like psoriatic arthropathy which involves the joints, as well as various physiological, liver and cardiovascular conditions.² 

Clinical manifestations of psoriasis

Common symptoms include 

• Red, scaly, itchy or burning skin patches
• Dry, cracked skin
• Nail changes
•  Poor sleep quality¹

Types of psoriasis 

Mainly, there are five types of psoriasis, which include:

1. Plaque psoriasis
2. Guttate psoriasis
3. Pustular psoriasis
4. Inverse psoriasis
5. Erythrodermic psoriasis

Plaque psoriasis: A common type of psoriasis which presents as raised, red skin patches enclosed by white, silvery scales. Over the body, these patches appear to be in a symmetrical pattern on the trunk, scalp, and limbs, exclusively on the knees and elbows.

Guttate psoriasis: This is frequently seen in young adults and children, and appears on limbs or torso as small red dots. This type of psoriasis is triggered by upper respiratory infections caused by group A Streptococcus bacteria. 

Pustular psoriasis: This type involves pus-filled blisters on the skin often surrounded by red, inflamed skin, usually on the hands and feet, though it can affect the whole body. Stimulants include medications, infections, stress, and chemicals.

Inverse psoriasis: Is seen in areas like within the armpits or groin, and below the breast. This form of psoriasis presents as smooth, red patches in skin folds. This may be aggravated by rubbing and moisture from sweating.

Erythrodermic psoriasis: Is a rare, severe form involving widespread red, scaly skin, often triggered by sunburn or medications, and usually occurs in poorly controlled psoriasis cases.¹

Pustular psoriasis

Pustular psoriasis is a lasting skin condition marked by inflammation and different clinical patterns. The most common type,called psoriasis vulgaris or plaque psoriasis, makes up about 80% of cases. It usually results from genetic and environmental factors. Besides this common form, there are much rarer types known as pustular psoriasis or psoriasis-related subtypes. These are characterised by visible, sterile pustules caused by neutrophil-driven skin inflammation.³ Pustular psoriasis can be divided into two types based on the severity of the condition, as generalised pustular psoriasis and localised pustular psoriasis.⁴

Generalized pustular psoriasis(GPP)

Generalised pustular psoriasis (GPP) is a rare, intense psoriasis condition that flares intermittently, presenting as widespread pustule-covered rashes along with fever, fatigue, and joint pain.It has a very low prevalence, affecting 0.0002% of people in France and 0.0007% in Japan.³ GPP include recurrent events of pustule formation due to infiltration of immune cells in the skin, and in critical cases, can require hospitalisation.⁵

Lab investigations associated with GPP

• Raised C- reactive protein level (CRP)
• Low calcium (hypocalcemia) levels
• Low albumin (hypoalbuminemia)
• Elevated neutrophils (neutrophilia) 
• Liver function test (LFT) abnormalities⁶

Complications associated with GPP

The death rate is around 2 to 16% in cases of GPP are due to complications such as:

• Sepsis
• Heart failure (HF)
• Renal failure
• Hepatic failure
• Respiratory failure⁶

Subtypes of GPP

• Von Zumbusch Type: Characterised by widespread pustular eruptions accompanied by systemic symptoms such as fever and joint pain
• Annular Type: Features ring-shaped lesions with pustules located at the expanding edges
• Exanthematic Type: Presents as a sudden, short-lived pustular outbreak without systemic involvement
• Impetigo Herpetiformis: A rare variant of pustular psoriasis that occurs during pregnancy

Localised pustular psoriasis

Localised pustular psoriasis can occur in two forms such as: 

• Acrodermatitis Continua of Hallopeau: Involves pustules primarily on the fingers, toes, and nail beds
• Palmoplantar Pustulosis: Limited to pustular lesions on the palms of the hands and soles of the feet⁷

Treatment of pustular psoriasis 

Methotrexate

Methotrexate is an extensively used medication for autoimmune and autoinflammatory conditions.⁸ Methotrexate’s exact mechanism in psoriasis is unclear, but it likely works by interfering with nucleotide synthesis and altering adenosine levels through intracellular activation and enzyme inhibition.⁹ Even though the mechanism of methotrexate is unclear, its use in psoriasis shows that by inhibiting the target of rapamycin pathway, it restores the regulatory T cells immunosuppressive activity and has shown a low onset of activity. Also, it is contraindicated for use in pregnancy.⁸ 

Dosage and administration of methotrexate 

Methotrexate should be given at a dose of 5 to 15 mg/week by oral route, increasing dose by 2.5 mg/week until treatment response by the intramuscular route and for individuals greater than 70 years of age, a starting dose of 7.5mg/week and a maximum dose of 25 mg/ week is used.¹⁰ 

Methotrexate is effective for both psoriasis and psoriatic arthritis, often at similar doses, with lower doses used for maintenance. It can also improve psoriatic nail changes. In elderly patients, especially those over 80, much lower doses may be sufficient due to reduced kidney function. Complete clearance of psoriasis is not recommended to avoid overtreatment, as serious or fatal side effects are usually linked to overdose.⁹

Adverse effects associated with methotrexate

• Nausea
• Leucopenia
• Mild elevation of liver transaminases

Taking folic acid at a dose of 5 mg daily can reduce gastrointestinal side effects. Nausea is a common reason for stopping methotrexate, but can be managed with antiemetics like ondansetron. Serious side effects are rare with weekly dosing, though uncommon complications may include hair loss, mouth or skin ulcers, ataxia, folliculitis, tuberculosis reactivation, and psychiatric symptoms. Regular monitoring of liver function and complete blood counts enables most patients to safely continue treatment ⁹.

Cyclosporine

Cyclosporin functions as an immunosuppressant by blocking the calcineurin phosphatase signalling pathway.^8,9

Dosage of cyclosporine

Cyclosporin is given at a dose of 3.5-5 mg/kg/day through the oral route, if an adequate response is shown, the dose tapers down by 0.5 mg/kg every 2 weeks. It has a rapid onset of action and is most effective in the severe acute disease state.¹⁰

Adverse effects associated with cyclosporine 

• Hypertension
• High chances of infection
• Nephrotoxicity⁸

Long-term use of cyclosporine should be avoided as a result of the above mentioned adverse effects.

Acitretin

Acitretin is a retinoid and etretinate derivative. It is the preferred systemic retinoid therapy for treating severe psoriasis.⁹ 

Dosing of acitretin

Acitetin is given at a dose of 0.75 to 1.0 mg/kg/day as a starting dose and 0.125 to 0.25 mg/kg/day as a maintenance dose for several months through the oral route.¹⁰

Adverse effects associated with Acitretin

• Hepatotoxicity 
• Skeletal toxicity
• Hyperlipidemia
• Mucocutaneous toxicity
• Teratogenicity⁹

Summary 

Psoriasis is a chronic autoimmune condition with pustular forms causing severe symptoms. Systemic treatments include methotrexate, cyclosporine, and acitretin. Methotrexate and cyclosporine modulate immune activity but need monitoring due to side effects. Acitretin, is effective for severe cases, but poses teratogenic risks and other toxicities, requiring careful patient selection.