What is Acute Generalized Exanthematous Pustulosis?

Acute Generalized Exanthematous Pustulosis (AGEP) is a rare skin condition that causes small, non-itchy pustules (small bumps filled with pus) on a red base to appear and spread quickly. In the beginning, people thought AGEP was just a type of pustular psoriasis, but it was later recognized and classified as its own unique condition in 1980.

The majority of AGEP incidents are caused by a bad reaction to a medication, but there have also been cases triggered by infections or contact with certain physical elements. Even though AGEP typically resolves on its own, it can potentially lead to complications that affect the whole body. The best treatment is to identify and stop using the drug or remove the trigger that caused it.

AGEP is categorized with other serious skin reactions known as severe cutaneous adverse reactions (SCARs) as a type IV hypersensitivity reaction, which describes an immune response that causes tissue damage. However, researchers are still trying to fully understand what causes AGEP.

What Causes Acute Generalized Exanthematous Pustulosis?

Most of the time, Acute Generalized Exanthematous Pustulosis (AGEP) is a side effect of certain medications, commonly antibiotics. Some of the main culprits are beta-lactam antibiotics and macrolides. Other medications that could trigger AGEP are drugs for malaria, fungal, viral, and parasitic infections, cancer and arthritis drugs,
painkillers, anticonvulsants, and even certain substances used in medical imaging tests.

Aside from drugs, other known triggers include infections, spider bites, allergic reactions, herbal remedies, and a type of light treatment for skin conditions called psoralen-UVA. Unbelievably, in some instances, even corticosteroids, which are supposed to reduce inflammation, have been reported to cause AGEP. However, there are cases where the cause is still unknown or not clearly identified.

Other suspected drugs includes a wide range of antibiotics, antifungal and anti-infection drugs, painkillers including opioids and muscle relaxants, medications for the nervous system like anticonvulsants and antipsychotics, heart medications, drugs for respiratory issues, cancer medications, along with others. Other substances like metformin, proton pump inhibitors, antihistamines, steroids, topical agents, mercury, herbal remedies, vitamins, vaccines, anti-anemic preparations and anesthetics have also been reported to cause AGEP.

Risk Factors and Frequency for Acute Generalized Exanthematous Pustulosis

AGEP, also known as Acute Generalized Exanthematous Pustulosis, is a rare skin condition that comes about as a reaction to medications. Although it isn’t commonly reported, that doesn’t mean it doesn’t occur often. This is because it is easily confused with other types of drug reactions and in most cases, clears up on its own before a person can even see a dermatologist.

The condition can affect anyone, regardless of their age. A study conducted in 2022 observed patients aged between 1 to 93 and found that it was particularly common in those aged over 25, especially between the ages of 40 and 64.
The majority of AGEP cases occur in women, with them accounting for about 65 to 80% of the total reported cases.
The timing of when AGEP appears and disappears can vary depending on the medication that caused it. The rise of AGEP in women might partly be due to how their bodies break down drugs differently than men’s bodies.
Over 85% to 90% of AGEP cases are related to exposure to drugs. This suggests that it is more common in countries where there is a greater access and use of medications, like the drug pristinamycin in France which is known to cause AGEP.
AGEP can also be more common in people with certain genetic types involved in immune system activity, which includes HLA-B51, HLA-DR-11, and HLA-DQ3. People with gene mutations that lead to increased IL-36 signaling may also be at a higher risk.

Signs and Symptoms of Acute Generalized Exanthematous Pustulosis

AGEP, or Acute Generalized Exanthematous Pustulosis, typically appears as small non-follicular clean blisters on reddened skin. These blisters rapidly develop and spread, often accompanied by itching or a burning sensation. A person may also feel feverish. Commonly described as the size of a pinhead, these blisters can merge, become more noticeable, and may even cause the top layer of the skin to peel off when gently touched.

The symptoms usually start in areas where two skin areas touch or rub together (also known as flexural or intertriginous regions), before spreading to the trunk, limbs, and face over a few hours to a few days. The symptoms typically spare the palm of the hands and the soles of the feet. In some cases the lining of the mouth can be involved, but that is less common.

Over the course of a week or two, these blisters will peel off in a manner that is usually described as a collar-shaped ring. Additional symptoms that have been reported involve swollen lymph nodes or uncommon presentations that include purple patches, blisters, large blisters, or symptoms specifically affecting the face, neck, and chest. The rapid onset of symptoms, usually within ten or fewer days of exposure to the triggering medication, and disappearance within about 15 days, is a key indication that someone might have AGEP.

In some cases, such as when AGEP is triggered by particular types of medication like Hydroxychloroquine or Terbinafine, it may take much longer for the symptoms to fully resolve.

Testing for Acute Generalized Exanthematous Pustulosis

To figure out if someone has AGEP (a skin condition that causes tiny blisters to form on the skin), doctors will need to collect a detailed history from the patient which includes a physical exam and a rundown of the patient’s medications. In addition, a punch biopsy (a procedure where a small amount of skin is removed for testing) and blood tests could be useful in confirming the diagnosis and looking for signs of the condition in the body. The blood tests may include a complete blood count (CBC), a comprehensive metabolic panel (CMP) for checking out the health of the kidneys and liver, and C-reactive protein (CRP), which can show inflammation in the body.

The urgency of these tests (and if they need to be done in hospital or at an outpatient clinic) will depend on the patient’s symptoms and their overall stability. If the skin condition is particularly severe and overlaps with conditions like Stevens-Johnson syndrome or toxic epidermal necrolysis, the patient may need to be seen at a specialized burn unit.

A scoring system may be used to help establish the likelihood of AGEP. This system, often referred to as the EuroSCAR criteria or AGEP validation score, takes into account clinical information, lab results, and biopsy findings. The scoring system works as follows:

A score of 0 or less rules out AGEP.
A score between 1 and 4 means AGEP cannot be ruled out.
A score between 5 and 7 suggests AGEP is probable.
A score of 8 to 12 confirms a diagnosis of AGEP.

The score is based on a variety of features including presence and size of pustules (tiny, fluid-filled spots), skin redness, pattern of distribution of the skin changes, peeling of the skin after pustules settle, involvement of any mucous membrane, speed of onset and resolution of symptoms, presence of fever, and white blood cell count, among others. The biopsy findings also play a crucial role in the final score.

Doctors may also try to identify the medication causing AGEP, especially if the patient is on multiple medications. If provocation tests are needed to confirm the link to a specific medication, they shouldn’t be done until six weeks after the resolution of symptoms. Skin patch testing is recommended in this scenario. Also, while lymphocyte transformation tests and enzyme-linked immunospot assays show potential, they’re currently not commonly used due to availability constraints and the need for well-preserved, viable patient’s T-lymphocytes.

Treatment Options for Acute Generalized Exanthematous Pustulosis

If you’re treated for this skin condition, the very first step is to stop taking any drugs that might have caused it. After that, support treatments like topical ceramides, which help moisturize the skin, can be used. It’s also important to keep good hygiene to prevent any secondary infections. Other treatments can include topical corticosteroids to reduce inflammation, antipyretics for fever, and antihistamines for itching.

There are also treatments mentioned for hospitalized patients like systemic corticosteroids and other medications such as cyclosporine, acitretin, dapsone, infliximab, and intravenous immune globulin (IVIG). However, these are not generally given unless the condition is severe or isn’t improving. Although these treatments are available, there aren’t yet any official, evidence-based guidelines for treating cases that have not improved with supportive care. Therefore, all current treatment recommendations are based on individual case studies.

If a person has previously had this skin condition, it is advisable to avoid what is suspected of causing it in the future and making sure it is well documented in their medical records to prevent a recurrence.

When trying to diagnose AGEP, a skin condition with pustular (pus-filled) and peeling skin phases, doctors have to rule out other conditions with similar symptoms. These include:

Pustular psoriasis (a type of skin condition with pus-filled bumps)
Sneddon-Wilkinson disease, a certain type of rare skin condition
A type of skin rash similar to chickenpox
Pustular vasculitis, another skin condition with pus-filled bumps
Staphylococcal scalded skin syndrome, a severe skin infection caused by bacteria
Pustular erythema multiforme, a skin disorder associated with infections and medications
Bullous impetigo, a contagious skin infection
Bullous tinea, a fungal skin infection
Pemphigus foliaceous, pemphigus erythematosus, pemphigus vulgaris, all rare autoimmune skin disorders
Severe skin reactions to certain types of medication like Stevens-Johnson syndrome, toxic epidermal necrolysis or DRESS (which stands for drug reaction with eosinophilia and systemic symptoms)

Among these conditions, pustular psoriasis is often the hardest to distinguish from AGEP because of their similarity in symptoms.

What to expect with Acute Generalized Exanthematous Pustulosis

The outlook for AGEP, a type of skin reaction, is usually positive with symptoms typically improving or entirely disappearing within 15 days after stopping the medication that caused it. However, the exact recovery time can depend on the specific details of the triggering drug. For instance, hydroxychloroquine has a long-lasting effect, which could extend the duration of AGEP symptoms compared to other medications.

If a patient develops AGEP from a medication they need for managing long-term conditions like heart disease, inflammatory arthritis, or epilepsy, it’s important to find a suitable alternative treatment to maintain their overall health.

There has been some debate around the reported death rate of 2 to 5% associated with AGEP. It is unclear whether these deaths were solely due to AGEP or related to other health issues. Recent reports have noted deaths amongst patients with AGEP, but mostly these patients were already in frail health prior to developing AGEP. Also, some of these patients’ AGEP had actually improved before they died. Most of these deaths were due to severe infection or failure of multiple organs.

Possible Complications When Diagnosed with Acute Generalized Exanthematous Pustulosis

Acute generalized exanthematous pustulosis, or AGEP, has been known to lead to several complications. These complications include skin infections due to the peeling off of the skin, enlarged liver, swollen lymph nodes, liver damage, kidney damage, low levels of calcium in the blood, accumulation of fluid around the lungs, breathing difficulties, a significant decrease in white blood cell count, and in serious cases, it can affect multiple organs. However, it should be noted that such incidents are likely influenced by reporting bias and patient data from previous hospital records.

One study that reviewed 340 AGEP cases in the United States found that approximately 8% of patients had an acute kidney injury as indicated by a 1.5 fold increase from their regular creatinine levels. Furthermore, around 8.5% had a liver enzyme count that was at least double the upper normal limit. In severe or untypical cases where AGEP cannot be managed with supportive care and by discontinuing medication alone, the symptoms may resemble those of septic shock or lead to clinical overlaps with other conditions like TEN or DRESS. This may result in the involvement of multiple organs requiring additional treatments. However, such complications are rare and in most cases, the condition resolves once the medicine causing it is discontinued.

Preventing Acute Generalized Exanthematous Pustulosis

You can take comfort in knowing that a skin condition known as AGEP usually gets better on its own over time when the cause is removed, along with some treatment for symptoms. Prior studies showed a fatality rate of 2 to 5%, but it’s not clear if AGEP alone was the cause, as patients often had other health conditions.

Treatment typically includes creams to reduce inflammation, steps to prevent further skin infections, and lotions to help moisturize the skin as it peels. Most of the time, these measures are enough to manage the condition effectively.

If it’s not clear what caused the AGEP, a skin test could be performed at least six weeks after the symptoms have completely disappeared. However, simply avoiding what might have triggered the reaction and noting down this incident in the patient’s medical history can be equally useful, even without confirmatory tests.

Frequently asked questions

Acute Generalized Exanthematous Pustulosis (AGEP) is a rare skin condition that causes small, non-itchy pustules on a red base to appear and spread quickly.

Signs and symptoms of Acute Generalized Exanthematous Pustulosis (AGEP) include: - Small non-follicular clean blisters on reddened skin - Rapid development and spread of blisters - Itching or burning sensation - Feeling feverish - Blisters merging and becoming more noticeable - Top layer of the skin peeling off when gently touched - Symptoms starting in areas where two skin areas touch or rub together (flexural or intertriginous regions) - Spreading to the trunk, limbs, and face over a few hours to a few days - Typically sparing the palm of the hands and the soles of the feet - Involvement of the lining of the mouth in some cases, but less common - Blisters peeling off in a collar-shaped ring over the course of a week or two - Additional symptoms such as swollen lymph nodes or uncommon presentations involving purple patches, blisters, large blisters, or symptoms specifically affecting the face, neck, and chest - Rapid onset of symptoms within ten or fewer days of exposure to the triggering medication - Disappearance of symptoms within about 15 days - Longer resolution time in some cases triggered by specific medications like Hydroxychloroquine or Terbinafine.

Acute Generalized Exanthematous Pustulosis (AGEP) can be caused by certain medications, infections, spider bites, allergic reactions, herbal remedies, psoralen-UVA light treatment for skin conditions, and even corticosteroids.

The doctor needs to rule out the following conditions when diagnosing Acute Generalized Exanthematous Pustulosis: - Pustular psoriasis - Sneddon-Wilkinson disease - A type of skin rash similar to chickenpox - Pustular vasculitis - Staphylococcal scalded skin syndrome - Pustular erythema multiforme - Bullous impetigo - Bullous tinea - Pemphigus foliaceous, pemphigus erythematosus, pemphigus vulgaris (rare autoimmune skin disorders) - Severe skin reactions to certain types of medication like Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS (drug reaction with eosinophilia and systemic symptoms)

To properly diagnose Acute Generalized Exanthematous Pustulosis (AGEP), the following tests may be ordered by a doctor: 1. Detailed history from the patient, including a physical exam and a rundown of the patient's medications. 2. Punch biopsy: A small amount of skin is removed for testing. 3. Blood tests, which may include: - Complete blood count (CBC) - Comprehensive metabolic panel (CMP) to check the health of the kidneys and liver - C-reactive protein (CRP) to detect inflammation in the body. Additionally, a scoring system called the EuroSCAR criteria or AGEP validation score may be used to establish the likelihood of AGEP based on clinical information, lab results, and biopsy findings. Provocation tests may also be conducted to identify the medication causing AGEP, and skin patch testing is recommended in this scenario.

Acute Generalized Exanthematous Pustulosis (AGEP) can be treated by first stopping any drugs that may have caused it. Support treatments such as topical ceramides can be used to moisturize the skin, and good hygiene should be maintained to prevent secondary infections. Other treatments may include topical corticosteroids to reduce inflammation, antipyretics for fever, and antihistamines for itching. In severe or non-improving cases, hospitalized patients may receive systemic corticosteroids, cyclosporine, acitretin, dapsone, infliximab, or intravenous immune globulin (IVIG). However, there are currently no official evidence-based guidelines for treating cases that have not improved with supportive care, so treatment recommendations are based on individual case studies. It is also advisable for individuals who have previously had AGEP to avoid suspected triggers and ensure documentation in their medical records to prevent recurrence.

When treating Acute Generalized Exanthematous Pustulosis (AGEP), there can be several side effects and complications. These include: - Skin infections due to the peeling off of the skin - Enlarged liver - Swollen lymph nodes - Liver damage - Kidney damage - Low levels of calcium in the blood - Accumulation of fluid around the lungs - Breathing difficulties - Significant decrease in white blood cell count - In severe cases, it can affect multiple organs - Rarely, it may resemble septic shock or lead to clinical overlaps with other conditions like TEN or DRESS, requiring additional treatments It is important to note that these complications are rare, and in most cases, the condition resolves once the medication causing it is discontinued.

The prognosis for Acute Generalized Exanthematous Pustulosis (AGEP) is usually positive, with symptoms typically improving or disappearing within 15 days after stopping the medication that caused it. However, the exact recovery time can depend on the specific details of the triggering drug. In some cases, the duration of AGEP symptoms may be extended if the triggering medication has a long-lasting effect.

A dermatologist.