Unraveling the Triggers: What Causes Generalized Pustular Psoriasis (GPP)?

Introduction: Understanding Generalized Pustular Psoriasis (GPP)

Generalized Pustular Psoriasis (GPP) is a rare, severe, and potentially life-threatening form of psoriasis that manifests as widespread, painful, sterile pustules on reddened skin. Unlike plaque psoriasis, which typically involves scaly patches, GPP is characterized by sudden, acute flares that can lead to systemic inflammation and serious complications if not promptly managed. This condition can significantly impact a person's quality of life and requires specialized medical attention. Understanding the underlying causes and triggers of GPP is paramount for effective management, prevention of flares, and improved patient outcomes. This comprehensive guide will delve deep into the complex etiology of GPP, exploring genetic predispositions, immune system dysfunction, environmental factors, and medication-related triggers, while also outlining its symptoms, diagnosis, treatment, and preventive strategies.

Psoriasis, in general, is a chronic autoimmune disease that speeds up the growth cycle of skin cells, leading to thick, scaly patches. However, GPP stands apart due to its acute onset, the presence of widespread pustules, and the potential for systemic involvement. It's crucial for individuals experiencing symptoms suggestive of GPP to seek immediate medical consultation, as timely intervention can prevent severe complications and improve the prognosis. By shedding light on the intricate mechanisms behind GPP, we aim to empower patients and healthcare providers with the knowledge necessary to navigate this challenging condition.

What is Generalized Pustular Psoriasis (GPP)?

Generalized Pustular Psoriasis (GPP) is a distinct and severe inflammatory skin disease characterized by sudden, widespread eruptions of sterile pustules. These pustules are small, white, non-infectious bumps filled with white blood cells, appearing on a background of intensely red, inflamed skin. GPP can affect large areas of the body, often accompanied by systemic symptoms such as fever, fatigue, joint pain, and a general feeling of being unwell. Unlike plaque psoriasis, GPP flares can develop rapidly, sometimes within hours, and can be life-threatening due to potential complications like sepsis, cardiovascular issues, and kidney failure.

GPP is considered a medical emergency, and patients often require hospitalization for aggressive treatment and supportive care. It can occur in people who already have plaque psoriasis, or it can appear as the first manifestation of psoriasis. In some cases, GPP can be triggered by specific factors, while in others, it may arise spontaneously. The condition is rare, affecting an estimated 1-2 people per million, but its severity necessitates a thorough understanding of its mechanisms and management.

The Distinction: GPP vs. Other Psoriasis Types

While GPP is a form of psoriasis, it differs significantly from the more common plaque psoriasis. Plaque psoriasis, which accounts for about 80-90% of all psoriasis cases, is characterized by well-demarcated, red, scaly plaques. These plaques typically develop slowly and persist over time, with varying degrees of itching and discomfort. In contrast, GPP presents with acute, widespread eruptions of pustules, often accompanied by systemic symptoms. The skin in GPP is acutely inflamed, tender, and painful, distinguishing it from the chronic, sometimes less acutely painful, plaques of common psoriasis.

Another form, erythrodermic psoriasis, also involves widespread redness and inflammation but typically lacks the prominent pustules seen in GPP. Pustular psoriasis can also be localized, affecting only specific areas like the palms and soles (palmoplantar pustulosis). Generalized Pustular Psoriasis, however, specifically refers to the widespread involvement of the body's surface with pustules, signaling a more severe systemic inflammatory response.

Symptoms of Generalized Pustular Psoriasis

The symptoms of GPP are typically dramatic and appear suddenly, often escalating rapidly over hours to days. Recognizing these symptoms early is crucial for prompt diagnosis and intervention.

Skin Manifestations

• Widespread Pustules: The hallmark of GPP is the rapid appearance of numerous, small (1-2 mm), sterile, white or yellowish pustules. These pustules often cluster together and can merge, forming larger areas of pus. They typically develop on a background of intensely red, inflamed, and tender skin, covering large areas of the body, including the trunk, limbs, and sometimes the face.
• Erythema (Redness): The skin becomes diffusely red and inflamed before or alongside the eruption of pustules. This redness is often widespread and can be extremely painful to the touch.
• Skin Peeling and Crusting: As the pustules dry, the skin may peel in large sheets, leaving raw, tender areas. This can lead to significant skin barrier dysfunction, increasing the risk of infection and fluid loss.
• Pain and Itching: The affected skin is typically very painful, burning, and tender. While itching can occur, pain is often the more dominant and debilitating symptom.

Systemic Symptoms

Beyond the skin, GPP often triggers a systemic inflammatory response, leading to a range of non-dermatological symptoms:

• Fever and Chills: High fever (often above 100.4°F or 38°C) is a common accompanying symptom, reflecting the body's generalized inflammatory state. Chills may also be present.
• Fatigue and Malaise: Patients often experience profound fatigue, weakness, and a general feeling of being unwell (malaise).
• Joint Pain and Swelling: Arthralgia (joint pain) is common, and in some cases, joint swelling may occur, similar to psoriatic arthritis.
• Muscle Weakness: Generalized muscle weakness can contribute to the overall feeling of debilitation.
• Headache: Headaches are a frequent systemic complaint during GPP flares.
• Nausea and Vomiting: Gastrointestinal symptoms like nausea and vomiting can occur, further complicating fluid and electrolyte balance.
• Rapid Pulse (Tachycardia): The body's inflammatory response can elevate heart rate.
• Dehydration: Extensive skin inflammation and peeling can lead to significant fluid loss through the compromised skin barrier, increasing the risk of dehydration and electrolyte imbalances.

Progression of a GPP Flare

A GPP flare typically progresses through several stages:

1. Prodromal Phase: Some individuals may experience non-specific symptoms like fever, fatigue, and muscle aches a few days before the skin eruption.
2. Eruptive Phase: Sudden onset of widespread redness, tenderness, and rapid formation of pustules. The pustules may coalesce into larger patches of pus.
3. Desquamation Phase: As the pustules resolve, the inflamed skin begins to dry and peel in large sheets, often leaving the skin raw and vulnerable. This phase can last for several days to weeks.

GPP flares can recur, and the frequency and severity can vary greatly among individuals. Each flare carries the risk of serious complications, necessitating careful management.

The Complex Causes and Triggers of Generalized Pustular Psoriasis

The exact cause of GPP is multifaceted and not fully understood, but it involves a complex interplay of genetic predisposition, immune system dysfunction, and environmental triggers. While some cases may appear spontaneously, many flares are linked to specific precipitating factors.

Genetic Predisposition

Genetic factors play a significant role in the susceptibility to GPP. Research has identified several genes associated with an increased risk:

• IL36RN Gene Mutations: The most significant genetic link identified for GPP is mutations in the IL36RN gene, which encodes for the interleukin-36 receptor antagonist (IL-36Ra). IL-36Ra normally functions to regulate inflammation by inhibiting the activity of IL-36 cytokines, which are potent pro-inflammatory mediators in the skin. When there is a mutation in IL36RN, the IL-36Ra protein may be dysfunctional or absent, leading to uncontrolled activation of the IL-36 pathway. This results in excessive inflammation, neutrophil recruitment, and the characteristic pustule formation seen in GPP. This specific genetic condition is sometimes referred to as Deficiency of Interleukin-36 Receptor Antagonist (DITRA). Individuals with DITRA often experience earlier onset and more severe forms of GPP.
• CARD14 Gene Mutations: Mutations in the CARD14 gene have also been implicated in some cases of GPP. CARD14 is involved in the NF-κB signaling pathway, which plays a critical role in immune and inflammatory responses. Dysregulation of this pathway can contribute to chronic inflammation.
• AP1S3 Gene Mutations: Another gene, AP1S3, which is involved in autophagy (a cellular recycling process) and immune regulation, has been associated with GPP, particularly in specific populations.
• Other Psoriasis Susceptibility Genes: Beyond these specific GPP-related genes, individuals with a family history of plaque psoriasis or carrying other genes associated with general psoriasis susceptibility (e.g., HLA-Cw6) may also have an increased risk of developing GPP.

Immune System Dysregulation

GPP is fundamentally an autoimmune inflammatory condition. The immune system, for reasons still being fully elucidated, mistakenly attacks healthy skin cells and triggers an exaggerated inflammatory response. Key aspects of immune dysregulation include:

• IL-36 Pathway Activation: As mentioned, the IL-36 cytokine family (IL-36α, IL-36β, IL-36γ) are powerful pro-inflammatory signals in the skin. In GPP, there is an overactivation of this pathway, leading to a cascade of inflammatory events. This includes the recruitment and activation of neutrophils (a type of white blood cell), which accumulate in the skin to form the sterile pustules.
• Other Inflammatory Cytokines: While IL-36 is central, other inflammatory cytokines such as TNF-alpha, IL-17, and IL-23, which are also involved in plaque psoriasis, contribute to the overall inflammatory milieu in GPP. The interplay between these pathways leads to the severe and widespread inflammation.
• Neutrophil Accumulation: The massive influx of neutrophils into the epidermis is a defining pathological feature of GPP. These immune cells, while crucial for fighting infection, contribute to tissue damage and inflammation when inappropriately activated.

Medication Triggers

Certain medications are well-known to trigger or exacerbate GPP flares. This is one of the most identifiable and modifiable causes:

• Withdrawal of Systemic Corticosteroids: This is arguably the most common and significant medication trigger. Patients with severe psoriasis who are rapidly tapered off or abruptly stop systemic corticosteroids (e.g., prednisone) are at a high risk of developing a GPP flare. The sudden removal of the immunosuppressive effect of steroids can lead to a rebound phenomenon, where the immune system overreacts.
• Beta-blockers: Medications used to treat high blood pressure and heart conditions can sometimes trigger GPP.
• Nonsteroidal Anti-inflammatory Drugs (NSAIDs): Over-the-counter and prescription NSAIDs, such as ibuprofen and naproxen, can occasionally precipitate GPP flares in susceptible individuals.
• Lithium: Used in the treatment of bipolar disorder, lithium is a known trigger for various forms of psoriasis, including GPP.
• Antimalarials: Drugs like hydroxychloroquine, used for malaria and autoimmune diseases, can sometimes induce GPP.
• TNF-alpha Inhibitor Withdrawal: Similar to corticosteroids, stopping TNF-alpha inhibitors (biologics used for psoriasis and other autoimmune conditions) can sometimes lead to GPP flares in some patients.
• Other Drugs: Less commonly, certain antibiotics, iodides, and some calcium channel blockers have been reported as triggers.

Infections

Infections, particularly bacterial and viral, can act as potent triggers for GPP flares by stimulating the immune system:

• Bacterial Infections: Streptococcal infections (e.g., strep throat), staphylococcal infections, and other bacterial infections can lead to an exaggerated immune response that precipitates GPP.
• Viral Infections: Viral illnesses, including influenza and common colds, can also trigger flares.

The body's immune response to these pathogens can activate inflammatory pathways, leading to a GPP eruption.

Pregnancy (Impetigo Herpetiformis)

GPP can occur during pregnancy, a condition specifically known as impetigo herpetiformis. This is a rare, severe form of GPP that typically appears in the third trimester of pregnancy and resolves after delivery. Hormonal changes during pregnancy are thought to play a significant role in triggering this variant. Impetigo herpetiformis can pose risks to both the mother and the fetus and requires careful management.

Stress

Both physical and psychological stress can exacerbate or trigger GPP flares:

• Physical Stress: Surgery, trauma, severe sunburn, or other forms of physical injury can act as stressors that prompt a GPP flare.
• Psychological Stress: Emotional distress, anxiety, and significant life events can also contribute to flare-ups by influencing the immune system and inflammatory pathways.

Environmental Factors

Certain environmental conditions can also contribute to GPP flares:

• Sudden Temperature Changes: Rapid shifts in environmental temperature can sometimes trigger flares.
• Excessive UV Exposure: While controlled phototherapy is used for some psoriasis types, excessive or inappropriate UV exposure (e.g., severe sunburn) can sometimes trigger GPP.

Lifestyle Factors

While not direct causes, certain lifestyle choices can influence the risk and severity of GPP:

• Smoking: Smoking is a known risk factor for various forms of psoriasis and can worsen disease severity and increase the likelihood of flares.
• Alcohol Consumption: Heavy alcohol intake can also exacerbate psoriasis and may contribute to GPP flares.

Other Underlying Conditions

Rarely, other medical conditions can be associated with GPP:

• Hypocalcemia: Low levels of calcium in the blood have been reported as a trigger for GPP in some cases.

In many instances, GPP flares may be multifactorial, meaning a combination of several triggers acting together or in sequence leads to the eruption.

Diagnosing Generalized Pustular Psoriasis

Diagnosing GPP requires a thorough clinical evaluation, often supported by laboratory tests and a skin biopsy. Due to its severity and the need for rapid treatment, prompt diagnosis is critical.

Clinical Examination

A dermatologist or emergency physician will perform a comprehensive physical examination, focusing on the skin lesions and assessing for systemic symptoms. The characteristic widespread erythema and sterile pustules are key diagnostic indicators. The physician will also look for signs of systemic inflammation such as fever, rapid pulse, and signs of dehydration.

Skin Biopsy

A skin biopsy is often performed to confirm the diagnosis and differentiate GPP from other pustular skin conditions. Histopathological examination of a skin sample typically reveals:

• Spongiform Pustules of Kogoj: These are characteristic collections of neutrophils within the epidermis.
• Neutrophilic Infiltrates: A dense presence of neutrophils in the dermis.
• Epidermal Hyperplasia: Thickening of the epidermis.

The absence of bacteria or other pathogens in the pustules (sterility) helps confirm the diagnosis and rule out infectious causes.

Blood Tests

Blood tests are essential for assessing systemic involvement and ruling out other conditions:

• Complete Blood Count (CBC): May show an elevated white blood cell count (leukocytosis), particularly neutrophils, indicating inflammation. Anemia may also be present.
• Inflammatory Markers: Elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are common, reflecting systemic inflammation.
• Electrolyte Levels: Important to check for imbalances due to fluid loss through compromised skin.
• Liver and Kidney Function Tests: To assess the function of these organs, which can be affected by severe inflammation or certain treatments.
• Calcium Levels: To rule out hypocalcemia as a potential trigger.
• Blood Cultures: May be taken to rule out sepsis, especially if there is a high fever or signs of systemic infection.

Differential Diagnosis

It is important to differentiate GPP from other conditions that can present with pustules or widespread redness, such as:

• Acute Generalized Exanthematous Pustulosis (AGEP): A drug-induced reaction characterized by numerous small pustules, often with fever. A skin biopsy and drug history are crucial for differentiation.
• Bacterial Infections: Such as staphylococcal scalded skin syndrome or cellulitis, which would show positive bacterial cultures.
• Erythroderma: Widespread redness, but typically without prominent pustules.
• Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) Syndrome: A severe drug reaction that can cause widespread rash and systemic symptoms, but often with eosinophilia and organ involvement.

The combination of clinical presentation, biopsy findings, and laboratory results helps establish a definitive diagnosis of GPP.

Treatment Options for GPP

Treatment for GPP is typically initiated in a hospital setting due to the severity and potential for rapid deterioration. The goals are to quickly suppress inflammation, alleviate symptoms, prevent complications, and identify/manage triggers.

Acute Flare Management

• Hospitalization: Most patients with acute GPP flares require hospitalization for close monitoring, aggressive treatment, and supportive care.
• Systemic Therapies: These are the mainstay of acute GPP treatment:
  • Oral Retinoids (e.g., Acitretin): Often considered a first-line treatment for GPP. Acitretin helps normalize skin cell growth and reduce inflammation. It can be effective but has a slower onset of action compared to some other options.
  • Cyclosporine: A potent immunosuppressant that works quickly to control inflammation. It is often used for severe flares but requires careful monitoring of kidney function and blood pressure.
  • Methotrexate: Another immunosuppressant that can be effective for GPP, though its onset of action might be slower than cyclosporine. Liver function and blood counts need to be monitored.
  • Systemic Corticosteroids: While withdrawal can trigger GPP, high-dose systemic corticosteroids (e.g., prednisone) may be used cautiously in the acute phase to rapidly suppress inflammation, especially in life-threatening situations. However, they are generally tapered slowly to avoid rebound flares.
• Targeted Biologic Therapies:
  • Spesolimab (Spevigo): This is an IL-36 receptor antagonist, the first FDA-approved treatment specifically for GPP flares. It works by blocking the IL-36 pathway, which is hyperactive in GPP, thereby rapidly reducing inflammation and pustule formation. It has shown rapid and significant efficacy in clinical trials.
  • TNF-alpha Inhibitors (e.g., Infliximab, Adalimumab): While primarily used for plaque psoriasis, these biologics can be considered for GPP, especially in patients who do not respond to conventional systemic therapies or for long-term management.
  • IL-17 Inhibitors (e.g., Secukinumab, Ixekizumab): These biologics target IL-17, another key cytokine in psoriasis pathogenesis, and may be used in some cases of GPP.
  • IL-23 Inhibitors (e.g., Guselkumab, Risankizumab, Tildrakizumab): These agents target IL-23, an upstream cytokine in the inflammatory pathway, and are also being explored for GPP.

Supportive Care

Crucial for managing the systemic effects and complications of GPP:

• Fluid and Electrolyte Management: Intravenous fluids may be necessary to correct dehydration and electrolyte imbalances resulting from extensive skin involvement.
• Pain Management: Strong analgesics are often required to manage the severe skin pain.
• Wound Care: Gentle skin care, including emollients and non-irritating dressings, is important to protect compromised skin and prevent secondary infections.
• Temperature Regulation: Patients may have difficulty regulating body temperature, requiring measures to prevent hypothermia or hyperthermia.
• Nutritional Support: Adequate nutrition is vital, especially if the patient is severely ill or has difficulty eating.

Long-Term Management

Once the acute flare is controlled, the focus shifts to preventing future flares and maintaining disease remission. This often involves continued use of systemic therapies (e.g., retinoids, methotrexate, biologics) at maintenance doses, careful monitoring, and trigger avoidance. The choice of long-term therapy depends on individual patient factors, response to acute treatment, and potential side effects.

Prevention and Management of GPP Flares

Preventing GPP flares is a critical aspect of managing the condition and improving patient quality of life. This involves a proactive approach to identifying and mitigating risk factors.

Identifying and Avoiding Triggers

Patients with GPP should work closely with their healthcare provider to identify potential triggers and develop strategies to avoid them:

• Medication Management: Carefully manage any medications known to trigger GPP. If systemic corticosteroids are used, ensure a very slow and gradual taper under strict medical supervision. Avoid abrupt discontinuation of other systemic therapies or biologics without consulting a doctor. Inform all healthcare providers about your GPP diagnosis and specific medication sensitivities.
• Infection Control: Promptly treat any infections, whether bacterial or viral. Practice good hygiene, get recommended vaccinations (e.g., flu shot), and avoid close contact with sick individuals.
• Stress Reduction: Implement stress-management techniques such as meditation, yoga, mindfulness, or counseling. Recognize and address sources of psychological stress.
• Environmental Awareness: Be mindful of sudden temperature changes. Protect skin from severe sunburn.
• Lifestyle Modifications: If applicable, cease smoking and reduce alcohol consumption. Maintain a healthy, balanced diet and regular, moderate exercise.
• Pregnancy Planning: Women with GPP who are planning pregnancy should discuss their condition and medication use with their dermatologist and obstetrician to develop a safe management plan.

Adherence to Treatment

Consistent adherence to prescribed maintenance therapies is crucial for preventing flares. Skipping doses or discontinuing medication without medical advice can significantly increase the risk of recurrence.

Regular Monitoring

Regular follow-up appointments with a dermatologist are essential to monitor disease activity, assess treatment effectiveness, and adjust therapy as needed. Blood tests may be required periodically to monitor for side effects of medications and detect early signs of inflammation.

Patient Education

Educating patients about their condition, potential triggers, and the importance of early intervention is vital. Patients should be taught to recognize the early signs of a flare-up so they can seek medical attention promptly.

When to See a Doctor

GPP is a medical emergency. You should seek immediate medical attention if you experience any of the following:

• Sudden onset of widespread redness and tenderness of the skin.
• Rapid appearance of numerous small, white or yellowish pustules over large areas of your body.
• High fever, chills, or a general feeling of being unwell (malaise) accompanying skin changes.
• Severe pain or burning sensation in the affected skin.
• Signs of dehydration, such as excessive thirst, decreased urination, or dizziness.
• Any worsening of existing psoriasis that seems unusual or more severe than typical flares.

If you have been diagnosed with GPP, it is important to have an action plan with your dermatologist for what to do at the first sign of a flare, which may involve immediate contact with your doctor or visiting an emergency room.

Frequently Asked Questions (FAQs) about GPP

Q1: Is Generalized Pustular Psoriasis contagious?

No, Generalized Pustular Psoriasis is not contagious. It is an autoimmune condition, meaning it results from a dysfunction in your body's immune system, not from an infection that can be spread from person to person. The pustules are sterile, meaning they do not contain bacteria or viruses.

Q2: What is the difference between GPP and common plaque psoriasis?

Plaque psoriasis is characterized by chronic, well-defined, red, scaly patches. GPP, on the other hand, presents with acute, widespread eruptions of sterile pustules on a background of intensely red, inflamed skin, often accompanied by severe systemic symptoms like fever and fatigue. GPP flares can be life-threatening and require immediate medical attention, unlike typical plaque psoriasis which is generally not considered a medical emergency.

Q3: Can GPP be cured?

Currently, there is no cure for GPP. It is a chronic condition that can have recurrent flares. However, with effective treatment and careful management, GPP can be controlled, and flares can be prevented or significantly reduced in severity and frequency. Ongoing research continues to identify new and more targeted therapies.

Q4: Is GPP life-threatening?

Yes, GPP can be life-threatening if not treated promptly and effectively. Severe flares can lead to serious complications such as sepsis (a severe systemic infection), cardiovascular issues, kidney failure, and severe fluid and electrolyte imbalances. The extensive inflammation and skin barrier disruption can put significant strain on the body's organs. Early diagnosis and aggressive treatment are crucial for improving outcomes.

Q5: Are there specific dietary recommendations for GPP?

While there are no universally accepted specific dietary recommendations proven to treat or prevent GPP, maintaining a healthy, balanced diet is generally beneficial for overall health and immune function. Some individuals with psoriasis report that certain foods worsen their symptoms, but this is highly individual. It's advisable to discuss any dietary changes with your healthcare provider or a registered dietitian, especially if you have other health conditions.

Q6: Can GPP affect internal organs?

While GPP primarily manifests on the skin, the severe systemic inflammation it causes can affect internal organs. Complications can include liver dysfunction, kidney damage, cardiovascular strain, and in severe cases, multi-organ failure. The body's widespread inflammatory response and potential for sepsis are what make GPP a systemic disease with potential internal organ involvement.

Conclusion

Generalized Pustular Psoriasis (GPP) is a severe, debilitating, and potentially life-threatening form of psoriasis that demands immediate attention and specialized care. Its complex etiology, involving genetic predispositions, immune system dysregulation, and a variety of environmental and medication-related triggers, underscores the need for a comprehensive understanding of the disease. Recognizing the acute onset of widespread pustules, intense erythema, and systemic symptoms like fever is crucial for timely diagnosis.

While there is no cure, significant advancements in treatment, including targeted biologics like spesolimab, offer new hope for rapidly controlling flares and improving long-term management. Effective prevention strategies, centered on trigger avoidance and strict adherence to treatment regimens, are paramount in reducing the frequency and severity of GPP episodes. Patients with GPP, along with their families and healthcare providers, must work collaboratively to navigate this challenging condition, ensuring prompt medical intervention at the first sign of a flare and fostering a proactive approach to ongoing care. Continued research into the precise mechanisms of GPP holds the promise of even more effective and personalized treatments in the future.

Sources / Medical References

• Crowley, J. J., et al. (2021). "Generalized Pustular Psoriasis: A Guide to Its Clinical Features, Diagnosis, and Management." Journal of the American Academy of Dermatology, 84(6), 1675-1683.
• Ehrlich, A., et al. (2020). "Generalized Pustular Psoriasis: An Update on Pathogenesis and Treatment." American Journal of Clinical Dermatology, 21(5), 659-672.
• Twelves, S., et al. (2021). "The IL-36 Pathway: A Promising Therapeutic Target in Pustular Psoriasis." British Journal of Dermatology, 185(1), 27-38.
• Bachelez, H., et al. (2021). "Spesolimab for Generalized Pustular Psoriasis Flare." New England Journal of Medicine, 385(26), 2431-2440.
• Healthline: Generalized Pustular Psoriasis Causes. Available at: https://www.healthline.com/health/psoriasis/generalized-pustular-psoriasis-causes
• American Academy of Dermatology Association: Psoriasis. Available at: https://www.aad.org/public/diseases/psoriasis/what/generalized-pustular
• National Psoriasis Foundation: Generalized Pustular Psoriasis (GPP). Available at: https://www.psoriasis.org/about-psoriasis/types/generalized-pustular-psoriasis/