What is GPP? 

Generalized Pustular Psoriasis (GPP) is a rare form of psoriasis that causes painful pus-filled bumps called pustules to emerge all over the body ⁽¹⁾. It is often accompanied with fever, shivers and itching.   This is in contrast to localized pustular psoriasis, which is confined to one area of the body ⁽²⁾.  

GPP is a systemic autoimmune disease characterized by sudden flares that last a few weeks and then remit where the pustules partly or completely resolve. The pustules are filled with white or yellow pus which is a collection of dead white blood cells and does not represent an infection nor is it contagious. Rarely in GPP these small pustules can even come together and form irregular “lakes of pus^{” (2)}.

GPP flares may become serious and even life threatening, if left untreated.  During a flare, complications can arise such as serious infection since the skin is no longer able to protect itself from infections and may be unable to keep your body help.  Although these complications and rare and may never happened to someone experiencing a GPP flare, it is important to see medical care right away if you suspect you are having a flare. ⁽⁶⁾

It is important to know that GPP is NOT contagious. 

Signs and Symptoms 

Being able to recognize GPP symptoms early is important to getting a quick diagnosis and treatment. 

GPP symptoms can be unpredictable, and they can appear very suddenly.  

GPP is characterized by sudden flares followed by periods of no disease activity.  During a flare, people living with GPP experience widespread rash of pustules (2-3 mm) that is can be accompanied by red, extremely itchy, dry, and scaly cracked skin in the areas affected ^{(1, 2)}. People with GPP may experience more general symptoms like fever, chills, headache, fatigue, joint pain and muscle weakness ^(1,3).   A GPP flare may also cause serious life-threatening complications and may require immediate medical attention. 

What Causes GPP

Although the exact cause of GPP is still unclear, current evidence demonstrates that there may be some genes that increase the chances of developing GPP ^(2,4). These genetic mutations have been found to involve the IL-36 cytokine pathway which regulates inflammation ^(2,4). Ultimately, a small part of the immune system becomes unbalanced and the signaling pathways that promote inflammation are overactive, leading to skin damage and systemic inflammation ⁽²⁾.

Difference between GPP and Plaque Psoriasis

GPP can be mistaken for plaque psoriasis, and while they are related, they are 2 distinct diseases.  Although different, people can experience both GPP and plaque psoriasis, in fact about 54% of people living with GPP also have plaque psoriasis) ⁽³⁾. 

Plaque psoriasis is defined by raised, inflamed, and scaly patches of skin that may be itchy and painful and it is considered an autoimmune condition.  GPP is different from plaque psoriasis genetically, physically and in its pathology.  ^{(4, 5, 6)}. GPP is considered to be a disease of the innate immune system, specifically neutrophilic, while plaque psoriasis is considered to be a disease of the adaptive immune system (6). Although GPP and plaque psoriasis have overlapping inflammatory pathways, the IL-36 pathway predominately drives GPP while the IL-23 pathway drives plaque psoriasis ⁽⁶⁾. Although plaque psoriasis and GPP can coexist the main distinguishing feature is widespread pus-filled bumps on erythematous skin ^{(4, 5, 6}). Unlike plaque psoriasis, these lesions tend to be tender on palpation ⁽⁴⁾.  

Risk factors and Epidemiology

Although we still don’t know what causes GPP to occur, it is associated with many genetic and environmental risk factors.  

Ethnicity: Although GPP prevalence varies across ethnicity and geographical regions, recent estimates found a high prevalence in US, Sweden, and Japan. The prevalence is approximately 9 per 100,000 in Sweden and the US, and around 3 per 100,000 in Japan ⁽¹⁾.  

Age: GPP  usually affects adults and is most common among adults aged 40-50, but children can develop GPP, although it is rare among the pediatric population ⁽⁷⁾.  

Gender: Females are more likely to be affected than males, however, for pediatric onset (3-16 years of age), males are more commonly affected ⁽⁷⁾.  

Pregnancy: pregnant women may develop a rare form of GPP called impetigo herpetiformis, which can be associated with risks for the fetus, although this is rare. The mechanism behind the unique susceptibility of pregnancy to GPP is unclear, but may be associated with increased progesterone levels, hypocalcaemia, low vitamin D level, hypoparathyroidism, and low elafin levels (an epidermal skin-derived antileukoproteinase) in combination with genetic predisposition ^{(7, 8)}.  

Previous Plaque Psoriasis: plaque psoriasis and GPP are strongly associated with one another, where having plaque psoriasis previously or concurrently increases one’s risk of developing GPP ⁽⁷⁾.  

Chronic conditions: a few studies have shown that GPP is associated with inflammatory polyarthritis and metabolic disorders such as obesity, hypertension, dyslipidemia, and diabetes ^(4). 

Infections: viral and bacterial infections are common triggers or exacerbating factors of GPP ⁽⁴⁾.  

Drugs: The rapid tapering of systemic corticosteroids  in patients that have a history of psoriasis can be a drug-related trigger of GPP. Other drugs that have been implicated include: terbinafine, propranolol, bupropion, lithium, phenylbutazone, salicylates, and potassium iodide however these would be exceedingly rare ⁽⁴⁾. 

Psychological stress: Patients describe precipitation of symptoms during times of stress ⁽⁹⁾.  

Complications: Complications widespread GPP include systemic infections and sepsis, loss of thermoregulation, fluid loss through hypovolemia, and metabolic disturbances ⁽⁷⁾. GPP can lead to acute respiratory distress syndrome (ARDS), congestive heart failure, renal failure, neutrophilic cholangitis, osteoarthritis, and uveitis ⁽⁹⁾. In some cases, if left untreated, GPP can lead to hospitalization and death ⁽⁹⁾.  

Treating GPP 

Many of the same treatment option used to treat psoriasis have been used to treat GPP.  

Non-pharmacological treatments: emollients and moisturizers, intravenous fluids and electrolytes, and analgesia. If pregnant it is important monitor the fetus and mother ⁽⁷⁾. 

Pharmacological treatments ^{(7, 4)}:  

• Topical agents: Calcipotriol,Tacrolimus,topical steroids
• Phototherapy— usually in combination with systemic agents.
• Antibioticsin the case of secondary bacterial infection.
• Non-biologic agents: First-line agents: Ciclosporin, Methotrexate, Oral retinoids (acitretin)
• Biologic agents: TNFα antagonistsadalimumab, infliximab, etanercept, Interleukin 17 (IL-17) antagonist— brodalumab, secukinumab, ixekizumab, bimekizumab;Interleukin 23 (IL-23) and 12 (IL-12) antagonists — guselkumab, risankizumab, ustekinumab; Interleukin 1 (IL-1) antagonists — anakinra, canakinumab, gevokizuma; Interleukin 36 (IL-36) antagonists —   

While these treatments are use in the treatment of GPP, spesolimab is the only drug that has done clinical trials in GPP and it is currently, the only drug with an official indication for treatment of GPP and that is approved by Health Canada for the treatment of flares in adult patients living with GPP.

Living with GPP

Individuals with GPP experience painful and uncomfortable flares that interfere with personal and social lives. Living with the symptoms of GPP and subsequent limitations in daily activities can cause anxiety and depression. People with GPP may be reluctant to attend life events, socialize with friends and family and be intimate with a spouse or partner due to the presence of pustular lesions or stigma ^{(1, 10, 11)}. 

Years without a diagnosis, the intensity and unpredictable nature of flares cause worry and stress for people living with GPP ^{(1, 10, 11)}. People with poorly managed GPP may experience lengthy hospitalization or live with long-term disability associated with complications (1, 10). This condition has far-reaching impacts beyond the patient ⁽¹⁾. Family members often witness their loved ones go through this debilitating condition and provide care to them ⁽¹⁾. There are also impacts to the healthcare system due to extended hospitalization and emergency care ⁽¹⁾.  

Living with GPP is not easy, but it is important ot remember that there are things that you can do to help manage your disease and symptoms. Finding a network of support in family and friends can help, or getting involved with a patient organization or other online communities can help you to connect with others who are going through the same experiences as you.  

Find a dermatologist that has experience with GPP can help you to better manage your conditions.  Ask us how you can find a dermatologist in your area!  

Taking care of your overall health can be important part of managing your condition.  Regular exercise, reducing alcohol consumption and a healthy diet can help.  Stress can cause a GPP flare, so recognizing and reducing stressors in your life can help. Self-care and a supportive community can go a long way in helping you in your GPP journey.  

How to support someone with GPP ⁽¹¹⁾ 

• Remind them they are not alone- check in with them and affirm you are always there for them.
• Flares can be unpredictable- tell them it is OK if they need to cancel plans at the last minute.
• Encourage them to seek treatment at the first sign of a flare- GPP does not go away by itself, and a flare can be life-threatening.
• Help them maintain a positive attitude and encourage them to partner with their doctor to find treatments that work for them.
• Offer to pick up their medication, give them a ride to the doctor, or other things they might need.

References:

1. Generalized pustular psoriasis (GPP): a rare, chronic, systemic disease. Boehringer. (n.d.). https://www.boehringer-ingelheim.com/human-health/skin-diseases/gpp/generalized-pustular-psoriasis-gpp-rare-chronic-systemic-disease
2. Upham, B. (2022, December). What is generalized pustular psoriasis? symptoms, causes, diagnosis, treatment, and prevention. EverydayHealth.com. https://www.everydayhealth.com/psoriasis/generalized-pustular-psoriasis/guide/ 
3. National Psoriasis Foundation. (n.d.). Generalized pustular psoriasis. The National Psoriasis Foundation: National Psoriasis Foundation. https://www.psoriasis.org/generalized-pustular-psoriasis/ 
4. Shah M, Al Aboud DM, Crane JS, et al. Pustular Psoriasis. [Updated 2023 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537002/
5. Pustular psoriasis - what does it look like and what are the different types?. Psoriasis and Psoriatic Arthritis Alliance (PAPAA). (n.d.). https://www.papaa.org/learn-about-psoriasis-and-psoriatic-arthritis/psoriatic-disease-unlocked/pustular-psoriasis/
6. Boehringer Ingelheim. . (n.d.-b). UNDERSTANDING GPP. Pro.boehringer. https://pro.boehringer-ingelheim.com/us/disease/gpp/understanding-gpp 
7. Neill, P. (2022, November). Generalised pustular psoriasis. DermNet. https://dermnetnz.org/topics/generalised-pustular-psoriasis
8. Ting, S. (2021, March). Pustular psoriasis of pregnancy. DermNet. https://dermnetnz.org/topics/pustular-psoriasis-of-pregnancy 
9. Boehringer Ingelheim. (n.d.). RECOGNIZING GPP FLARES. Pro.boehringer. https://pro.boehringer-ingelheim.com/us/disease/gpp/recognizing-gpp-flares
10. Boehringer Ingelheim. (n.d.). LIVING WITH GENERALIZED PUSTULAR PSORIASIS (GPP). Patient.boehringer. https://patient.boehringer-ingelheim.com/gpp/living-with-gpp 
11. Reisner DV, Johnsson FD, Kotowsky N, Brunette S, Valdecantos W, Eyerich K. Impact of Generalized Pustular Psoriasis from the Perspective of People Living with the Condition: Results of an Online Survey. Am J Clin Dermatol. 2022 Jan;23(Suppl 1):65-71. doi: 10.1007/s40257-021-00663-y. Epub 2022 Jan 21. PMID: 35061229; PMCID: PMC8777175.