Harshi Dhingra is a licensed medical doctor with specialization in Pathology. She is currently employed as faculty in a medical school with a tertiary care hospital and research center in India. Dr. Dhingra has over a decade of experience in diagnostic, clinical, research, and teaching work, and has written several publications and citations in indexed peer reviewed journals. She holds medical degrees for MBBS and an MD in Pathology.
Generalized pustular psoriasis (GPP) is a rare and severe immune-mediated disorder in which widespread pustules form on the skin.1
Pustules in GPP can affect large areas of the body, arms, and legs. The disease can result in serious complications that may require emergency medical treatment.2 Death can occur in this acute stage of GPP if the treatment rendered is incomplete or ineffective.3
There is an increased risk of chronic kidney disease/end-stage renal disease (CKD/ESRD) in GPP. However, the mechanism leading to kidney injury is not completely understood, and further research into the possible pathophysiology is required. The elevated risk may be due to metabolic and cardiovascular comorbidities or the administration of nephrotoxic drugs.4
One of the most frequent causes of CKD is atherosclerotic damage to the kidneys; often, people with GPP have accelerated atherosclerotic burden due to chronic damage to endothelial cells resulting from chronic inflammation.4
In GPP, there is direct inflammation and damage to the kidneys. The 2 known key regulatory cells implicated in the development of psoriasis are T helper (Th) 1 and Th17 lymphocytes. Inflammation is mediated through tubular epithelial cells, mesangial cells, and macrophages.4
Read more about GPP pathophysiology
The coexistence of glomerulopathy with psoriasis, mainly immunoglobulin A (IgA) nephropathy, can also contribute to the increased prevalence of CKD.4
Generalized pustular psoriasis is also associated with hypovolemia and oligemia, which can lead to acute kidney injury.3
Read more about GPP clinical features
Many liver function abnormalities are noted in association with GPP, including an increase in alkaline phosphatase levels.5 Abnormalities in liver function tests are noted in up to 90% of patients with GPP at the time of diagnosis. GPP is also associated with neutrophilic cholangitis.6 Cholestatic jaundice can occur as a result of neutrophilic cholangitis.3,7
Hepatic steatosis and metabolic syndrome can also occur with GPP. Hepatic steatosis is seen in 2% to 13.6% of GPP cases. Abdominal ultrasonography can be performed to detect steatosis. Risk factors for hepatic steatosis include diabetes, obesity, and increased lipid levels.6
Recent studies have linked GPP to IL36RN mutations (deficiency of interleukin-36 receptor antagonist [DITRA]). It has been hypothesized that IL36RN contributes to cancer growth and may be linked to hepatocellular carcinoma. A case study suggested that GPP with DITRA was precipitated by liver damage caused by hepatocellular cancer surgery.6
Read more about GPP genetics
First-line pharmacotherapies for GPP including Soriatane® (acitretin), methotrexate, cyclosporine, and other biologic therapies are also hepatotoxic.6
Read more about GPP treatment
Systemic Complications in Acute GPP
In the acute phase of GPP, systemic illness is noted.3 Systemic complications may include3,7:
- Marked hypoalbuminemia due to a sudden loss of plasma proteins into the tissues and malabsorption in the intestines
- Hypocalcemia due to hypoalbuminemia
- Acute respiratory distress syndrome (in rare cases)
- Staphylococcus infection, which can further complicate the disease
- Hair loss all over the body if the disease is prolonged
- Telogen effluvium 2 to 3 months after the disease peak
- Amyloidosis (may be a very late complication)
- Peripheral neuropathy
- Malabsorption of nutrients and medications
- Electrolyte disturbances and protein imbalances
- Cardiac failure
These complications can be life-threatening. Mortality may occur due to cardiorespiratory failure in the acute eruptive form of GPP. Therefore, it is crucial to manage the acute phase as early as possible. Older patients are at a higher risk of death.7
Read more about GPP life expectancy
Complications in Maternal GPP
Complications in maternal GPP can include preterm birth, fetal abnormalities, placental insufficiency, and even neonatal death.7
- Upham B. What is generalized pustular psoriasis? Symptoms, causes, diagnosis, treatment, and prevention. Everyday Health. Accessed May 17, 2023.
- Crowley JJ, Pariser DM, Yamauchi PS. A brief guide to pustular psoriasis for primary care providers. Postgrad Med. 2021;133(3):330-344. doi:10.1080/00325481.2020.1831315
- Mirza HA, Badri T, Kwan E. Generalized pustular psoriasis. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2023. Updated September 12, 2022. Accessed May 17, 2023.
- Ungprasert P, Raksasuk S. Psoriasis and risk of incident chronic kidney disease and end-stage renal disease: a systematic review and meta-analysis. Int Urol Nephrol. 2018;50(7):1277-1283. doi:10.1007/s11255-018-1868-z
- Warren DJ, Winney RJ, Beveridge GW. Oligaemia, renal failure, and jaundice associated with acute pustular psoriasis. Br Med J. 1974;2(5916):406-408. doi:10.1136/bmj.2.5916.406
- Lim LY, Oon HH. Gastrointestinal and hepatic manifestations in patients with generalised pustular psoriasis. Exp Dermatol. Published online February 13, 2023. doi:10.1111/exd.14766
- Neill P. Generalised pustular psoriasis. DermNet. November 2022. Accessed May 17, 2023.
Reviewed by Hasan Avcu, MD, on 5/18/2023.