Generalized pustular psoriasis

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Generalized pustular psoriasis (GPP) is a severe form of a skin disorder called psoriasis. GPP and other forms of psoriasis are caused by abnormal inflammation. Inflammation is a normal immune system response to injury and foreign invaders (such as bacteria). However, when inflammation is abnormal and uncontrolled, it can damage the body's tissues and organs. Individuals with GPP have repeated episodes in which large areas of skin become red and inflamed and develop small pus-filled blisters (pustules). The skin problems can be accompanied by fever, extreme tiredness (fatigue), muscle weakness, an increased number of white blood cells, and other signs of inflammation throughout the body (systemic inflammation). The inflammation problems subside and reappear often. Episodes can be triggered by infection, exposure to or withdrawal from certain medications, menstruation, or pregnancy, although the trigger is often unknown. GPP can be life-threatening if not treated.

While many affected individuals have features only of GPP (called GPP alone), some develop features of another skin condition called psoriasis vulgaris (PV), either before or after GPP appears. PV, the most common form of psoriasis, is characterized by red, scaly patches of skin (plaques) on parts of the body.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mutations in several genes, including IL36RN and CARD14, increase the risk of developing GPP. These two genes provide instructions for making proteins that play roles in regulating inflammation, particularly in the skin. The IL-36Ra protein, produced from the IL36RN gene, blocks the activity of specific proteins that trigger signaling pathways to promote skin inflammation. IL36RN gene mutations involved in GPP reduce the amount of IL-36Ra protein in the skin. Without control by IL-36Ra, signaling pathways that promote inflammation are overly active.

Conversely, the CARD14 protein normally turns on inflammation signaling. The CARD14 gene mutations associated with GPP increase the activity of the CARD14 protein, leading to uncontrolled inflammation signaling in the skin. Enhancement of these signaling pathways results in abnormal inflammatory reactions, which contribute to the skin problems and systemic inflammation characteristic of GPP.

IL36RN gene mutations are most often associated with GPP alone and are only rarely found in individuals who also have PV. Mutations in this gene appear to be the most common genetic risk factor for GPP alone. CARD14 gene mutations are more frequently found in individuals with both GPP and PV, although changes in this gene have also been found in individuals with GPP alone.

Many people with GPP do not have a mutation in the IL36RN or CARD14 gene. Mutations in other genes, some of which have not been identified, may also be associated with the condition. Having a gene mutation in one of the associated genes does not mean an individual will have GPP. Researchers suspect that environmental or other genetic factors help determine whether an individual will develop the condition.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

When associated with IL36RN gene mutations, risk of GPP is typically inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene.

When associated with CARD14 gene mutations, GPP risk is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase the risk of the disorder. In some cases, an affected person inherits the mutation from one parent. Other cases result from new (de novo) mutations in the gene.

People with mutations in either the IL36RN or CARD14 gene inherit an increased risk of GPP, not the condition itself. Not all people with this condition have mutations in one of these genes, and not all people with a mutation in one of these genes will develop the disorder.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

GPP is the rarest form of psoriasis. Although the worldwide prevalence of GPP is unknown, the condition is estimated to affect 2 per million people in Europe. It also occurs in approximately 0.6 per million people each year in Japan.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal nail morphology · Very frequent (99-80%)

Abnormal structure or appearance of the nail.

Arthralgia · Obligate (100%)

Joint pain.

Elevated erythrocyte sedimentation rate · Obligate (100%)

An increased erythrocyte sedimentation rate (ESR). The ESR is a test that measures the distance that erythrocytes have fallen after one hour in a vertical column of anticoagulated blood under the influence of gravity. The ESR is a nonspecific finding. An elevation may indicate inflammation or may be caused by any condition that elevates fibrinogen.

Erythematous plaque · Obligate (100%)

A plaque (a solid, raised, plateau-like (flat-topped) lesion greater than 1 cm in diameter) with a red or reddish color often associated with inflammation or irritation.

Erythroderma · Very frequent (99-80%)

An inflammatory exfoliative dermatosis involving nearly all of the surface of the skin. Erythroderma develops suddenly. A patchy erythema may generalize and spread to affect most of the skin. Scaling may appear in 2-6 days and be accompanied by hot, red, dry skin, malaise, and fever.

Pain · Very frequent (99-80%)

An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.

Pustule · Obligate (100%)

A small elevation of the skin containing cloudy or purulent material usually consisting of necrotic inflammatory cells.

Arthritis · Frequent (79-30%)

Inflammation of a joint.

Other findings in the same source

From: Orphanet

Additional reported features include Cheilitis (Frequent (79-30%)); Elevated circulating C-reactive protein concentration (Frequent (79-30%)); Fatigue (Frequent (79-30%)); Fever (Frequent (79-30%)); Geographic tongue (Frequent (79-30%)); Increased total leukocyte count (Frequent (79-30%)); Overweight (Frequent (79-30%)); Elevated circulating hepatic transaminase concentration (Occasional (29-5%)); Hypoalbuminemia (Occasional (29-5%)); Hypocalcemia (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Generalized pustular psoriasis is Dermatology, with a dermatologist as the relevant type of clinician. Dermatologist; paediatric services for children as appropriate.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which features of the skin, hair or nails distinguish the possibilities?
• Would photographs over time help document the changes?
• What should be expected from treatment, and how will irritation or other adverse effects be managed?

Treatment discussions and follow-up

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.