What is pustular psoriasis?

Pustular psoriasis (PP) is a type of psoriasis, considered an autoimmune condition that affects the skin. PP is not contagious; it is caused by an abnormal immune response; however, this means there is currently no cure. 

PP uniquely presents with additional small, yellowish pustules that contain white blood cells (inflammatory markers), and is different from the more common skin plaques seen in psoriasis. PP is usually considered idiopathic, meaning it arises spontaneously or the cause is unknown, though some genetic factors are involved in disease susceptibility. 

PP is divided into two subtypes

1. Localised form: palmoplantar pustular psoriasis (PPP), which affects the palms of the hands and soles of feet, and acrodermatitis continua of Hallopeau, which presents on fingers, toes, and nails and is now considered a subset of PPP¹
2. Generalised form: generalised pustular psoriasis (GPP), also called von Zumbusch, which can affect most of the body, annular and circinate pustular psoriasis, impetigo herpetiformis occurring during pregnancy, infantile pustular psoriasis, and juvenile pustular psoriasis²

PP can come and go throughout the lifetime. It is a rare, chronic condition with a varied, relapsing and remitting course.¹ Psoriasis can affect children, particularly in infancy, but is more common in adults, typically between the ages of 40 to 50.³ In general, it is more common in women, and the average age of onset is lower in individuals with GPP compared to those with PPP. 

Several risk factors may trigger the onset of PP:⁴

• Bacterial and viral infection
• Emotional stress
• Rapid withdrawal of medications
• Systemic illness
• Alcohol consumption
• Physical trauma to the skin

Physical stress - Can catching a cold cause PP?

Yes, an infection like the common cold can act as a triggering event, which causes the onset of psoriasis symptoms or the characteristics of the condition to change. These infections put a great deal of physical stress on our body’s immune system, which can cause it to misbehave and act abnormally in people with genetic predispositions to psoriasis and PP. 

Various microorganisms have been studied and reported as triggers of several types of psoriasis.⁵ Investigation of the characteristics of psoriasis induced by infection helps to achieve a better understanding of the disease process and also guides treatment strategies. However, further research is needed to better understand these processes. According to studies, infectious factors can carry a ‘superantigen’ (foreign protein) that acts on our immune cells to stimulate an excessive immune response,⁶ causing them to produce inflammatory markers that enhance skin cell growth and proliferation, promoting the varied symptoms of psoriasis.⁷

Bacterial infection as a trigger of PP

Tonsillar infections like strep throat, caused by Streptococcus pyogenes, can be a trigger for an abnormal immune response like PP. Researchers have identified certain genes that increase the risk of streptococcal throat infections that are likely associated with psoriasis.⁵ In such individuals, tonsillectomy is considered to be a valid intervention to help prevent triggering events in psoriasis. 

Staphylococcus aureus is another bacterium, commonly known to cause staph infections, that has also been considered a triggering event associated with the onset or development of psoriasis.  Moreover, the staphylococcal infection factors are correlated with a more severe form of psoriasis.⁸

There is also research into Helicobacter pylori, which naturally colonises the human gastric mucosa, and has been associated with skin diseases such as psoriasis.⁹ This suggests there may be a greater link between gut health and skin health than we currently understand. 

Viral infection as a trigger for PP

Viral infections cause dysregulated immune responses in people, and this can trigger the skin inflammation seen in psoriasis. HIV is a condition that devastates the body’s immune response. Therefore, patients with an HIV infection have a strong possibility of developing psoriasis and present a higher degree of skin lesions (more severe) compared with other psoriatic patients.  

Hepatitis B virus and hepatitis C virus have also been associated with increased psoriasis,¹⁰ as well as Human papillomavirus. SARS-CoV-2 was also another viral pathogen reported to be responsible for the exacerbation of psoriasis and PP, due to increased levels of inflammatory markers (cytokines) in the plasma of infected patients.⁵

Fungal infection 

Various fungi have been identified to induce psoriasis by affecting the innate immune system in individuals who are genetically predisposed.⁵ Epidemiological studies have also shown an association between psoriasis and fungal infections, particularly those caused by Malassezia and Candida albicans, whereby these fungi upregulate skin growth factors.¹⁰

Medications as a trigger for PP

Some medications act as triggers for the onset of psoriasis or have been recorded to worsen the condition and cause PP. In most cases, it can be hard to say a drug is the causative event, mainly because the skin symptoms vary and may appear long after the start of the medication, or in some cases, the psoriasis flare-ups continue even after discontinuation of the medication⁸. Additionally, under the microscope, drug-related psoriasis looks almost the same as conventional psoriasis. 

Despite this, there have been studies that show some drugs are more likely to cause psoriasis flare-ups

• Lithium: Used for treating bipolarism and other psychiatric disorders.  Psoriasis is the most common skin side effect of lithium therapy.¹¹ This could be attributed to the interference with intracellular calcium channels that affects the proliferation and differentiation of skin cells⁵
• Beta-blockers: Treatment with beta-blockers reduces the cAMP level in the body. This is an important intracellular messenger that promotes cell differentiation and inhibits skin cell proliferation. The reduction of cAMP results in excessive proliferation of skin cells and a lack of differentiation, which leads to psoriasis flare-ups⁵
• Antimalarial drugs: They are frequently reported as causative agents of psoriasis flare-ups. It could be related to the alteration of the activity of enzymes involved in cell proliferation¹¹
• Nonsteroidal anti-inflammatory drugs (NSAIDs): They work by inhibiting the metabolism of arachidonic acid, which causes the accumulation of leukotrienes, and this has been postulated to exacerbate psoriasis⁵
• Antibiotics (especially tetracyclines): The association between antibiotics and psoriasis flare-ups is controversial because infections themselves can trigger psoriasis. The mechanism through which tetracyclines may cause psoriasis flare-ups is by reducing intracellular cAMP levels¹²
• Biological agents: Some studies reported that tumour necrosis factor inhibitors – used to treat Crohn's disease and rheumatoid arthritis - induced or exacerbated psoriasis⁵
• Corticosteroids: The main course of treatment for psoriasis is applying topical corticosteroids to the affected areas, but these can also be administered through systemic routes. Unfortunately, this treatment is also an important trigger, especially when there is a sudden withdrawal of corticosteroids.¹³ Additionally, changes in the type of psoriasis have also been observed, from non-pustular forms to pustular psoriasis, which is a more severe form¹⁴

Emotional stress as a trigger of PP

 Psychological stress can trigger or worsen psoriasis by disrupting the hormonal system and negatively impacting the immune and nervous systems.¹⁵ Stress most likely triggers psoriasis by activating the hypothalamic-pituitary-adrenal (HPA) axis, which increases the production of cortisol in the body.⁵

Cortisol is the main stress hormone in humans, and its receptor is widely present in skin cells. Under stressful conditions, elevated levels of cortisol impact the immune system, causing increased white blood cell proliferation and transport, including the secretion of chemical messengers and antibodies.¹⁶ In addition, cortisol suppresses the apoptosis (a type of cellular death) of skin cells; therefore, skin cells do not shed or get cleared away, leading to their excessive proliferation, typical of psoriasis. Cortisol is also known to stimulate vascular endothelial growth factor, a molecule involved in blood vessel growth, leading to enhanced delivery of immune messengers. All these events aggravate psoriasis development.⁵

When psoriasis is triggered or exacerbated by physical or emotional stress, another key mechanism is the activation of a certain type of immune cell, called mast cells (MCs). Stress stimulates the peripheral nerves in the skin to release molecules, called neuropeptides. These molecules activate the mast cells, leading to inflammation and increased skin irritation. 

Another molecule involved in stress response is the brain-derived neurotrophic factor (BDNF), a neurotransmitter that plays a role in changing the structure of the brain. BDNF helps grow blood vessels and new neurons, which is how the brain learns and adapts over time. Studies have shown that BDNF levels are decreased under chronic stress conditions, and are also reduced in psoriasis patients compared with the general population. It's thought that the BDNF skin-related function is to induce apoptosis in normal skin cells, but not in psoriasis, leading to an excessive production.¹⁵

In summary, the brain and skin communicate in both directions through the HPA axis. The brain responds to stress through the HPA axis and secretes endocrine hormones and neurotransmitters that act on the skin. The skin also sends signals associated with skin lesions to the brain. Whether this is the primary cause of the ongoing and recurrent flare-ups of psoriasis requires further investigation.¹⁶

Systemic illnesses as a trigger of PP

Various systemic illnesses have been linked to the onset or exacerbation of psoriasis. Among these, metabolic syndrome has been seen to be very common in patients with psoriasis. Various studies have linked obesity and high cholesterol to the onset or exacerbation of psoriasis, although the disease mechanism is still not clear. In general, adipose tissue can act as an immune organ in individuals with dysregulated lipid metabolism by releasing hormones and chemical messengers that modulate inflammatory responses and activate the immune system. Additionally, researchers have reported that dietary components may be involved in the exacerbation of psoriasis, suggesting that saturated fatty acids amplify psoriasis flare-ups.⁵

Some meta-analyses showed that psoriasis was also associated with diabetes mellitus, but also that people with psoriasis have an increased risk of developing diabetes mellitus. Type 2 diabetes is more frequently comorbid with psoriasis, while type 1 shares immune pathways with psoriasis but may not contribute directly to the pathogenesis of psoriasis.

Another meta-analysis showed that people with psoriasis are more likely to have hypertension. Some evidence also suggests that hypertension might increase the risk of developing psoriasis. However, the exact mechanism of this association is still unclear.⁸

Additionally, psoriasis is frequently found associated with autoimmune disorders, such as systemic lupus erythematosus, autoimmune thyroid disease, celiac disease, inflammatory bowel disease, especially Crohn's disease, multiple sclerosis, Sjögren's syndrome, vitiligo, and alopecia areata.¹⁷

Recent identification of the numerous associations with various comorbidities and other autoimmune disorders suggests common immune pathways and cellular mechanisms may direct disease processes of psoriasis.¹⁸

Summary

Psoriasis affects both children and adults, but is more common in adulthood and more often develops in women. PP  is a rare form of psoriasis characterised by additional yellowish pustules around the skin. It can be distinguished into localised forms, such as PPP, and generalised forms, such as GPP.. 

You must have a genetic predisposition to psoriasis, and stress on the body to trigger the symptoms of PP. Environmental factors that can trigger PP include: illness due to bacterial or viral infections, e.g., Strep throat or COVID-19, and systemic illnesses, such as diabetes and hypertension. Certain drugs and psychological stress are also known to worsen the condition of psoriasis; however, it is hard to pinpoint accurately.