What is Drug Induced Pemphigus?
Pemphigus refers to a rare set of autoimmune diseases that result in blistering of the skin and the lining of the mouth. These conditions are marked by widespread soft blisters and sores that appear on the skin and inside the mouth. Drug-induced pemphigus is due to a mix of biochemical interactions and the abnormal stimulation of B cells in the body. These cells then produce antibodies known as intracellular IgG, which attack proteins called desmogleins. This leads to the separation of cells in the skin’s surface layer, a process known as acantholysis. Various factors can trigger these diseases, but drugs are known to be the primary cause of pemphigus.
What Causes Drug Induced Pemphigus?
Pemphigus, a type of skin disease, is often triggered by certain drugs. These drugs can be grouped into categories based on their chemical structure, namely thiols, phenols, and drugs that aren’t either. Thiol drugs, which contain a chemical group known as sulfhydryl (-SH), are the most common cause of pemphigus. Examples of thiol drugs include penicillamine, captopril, and tiopronine. These drugs work by stimulating specific enzymes, leading to skin cell disruption.
Phenol drugs can interrupt the normal functioning of intercellular bonding by triggering skin cells to release substances that cause inflammation. These inflammation-causing substances, including tumor necrosis factor-alpha and interleukin-1, can also lead to skin cell breakdown. Noteworthy phenol drugs include aspirin, heroin, rifampin, and levodopa.
Other drugs that don’t fit into the thiol or phenol categories have also been connected to pemphigus. They could potentially cause skin cell disruption through alternate pathways such as triggering autoantibodies or changing the structure of target antigens on skin cells. This category includes drugs like non-steroid anti-inflammatory agents and calcium-channel blockers.
Risk Factors and Frequency for Drug Induced Pemphigus
Pemphigus is a rare condition, with only 1 in every 100,000 people getting it. The most common cause of this disease is medication, making it a drug-induced condition. Pemphigus vulgaris is the most common type, and it’s particularly frequent among Jewish and Mediterranean people. Pemphigus appears to affect men and women equally, and it typically occurs between the ages of 40 to 60. Some common drugs that can potentially lead to this condition include D-penicillamine, captopril, and penicillin. Taking D-penicillamine, in particular, for six months has resulted in a pemphigus occurrence rate as high as 7% in one study.
- Pemphigus is a rare disease, affecting 1 in 100,000 people.
- The most common cause is drug-induced pemphigus.
- Pemphigus vulgaris is the most common type.
- This disease is more prevalent among Jewish and Mediterranean people.
- Both men and women get pemphigus equally, usually between the ages of 40 to 60.
- The drugs D-penicillamine, captopril, and penicillin can cause the disease.
- Taking D-penicillamine for six months can increase the rate of pemphigus to as high as 7% as per one study.
Signs and Symptoms of Drug Induced Pemphigus
Pemphigus vulgaris and pemphigus foliaceus can sometimes be caused by certain medications like d-penicillamine. Knowing a patient’s history of medication use and how long they’ve been exposed to it, can help identify the cause. The identifying signs of these conditions include limp or damaged spots on the skin. Doctors need to fully check the mouth, vagina, and the entire surface of the skin when looking for these signs.
- Pemphigus vulgaris often begins as soft, easily burst blisters on the mouth’s surface and the skin. These blisters and vesicles are full of a clear fluid and break easily. The first small blisters generally pop up on the scalp, face, chest, underarm, groin or back. Eventually, these lesions can spread to a large portion of the body, forming a collection of limp blisters and damaged areas. The lesions don’t usually cause itchiness, but can be extremely painful, as the blisters often burst and peel off the top layer of the skin.
- On the other hand, Pemphigus foliaceous usually doesn’t affect the lining of the mouth and starts with scaly crusted sores on a reddened base. The first distinct sores often appear on oily areas of the face, scalp, chest, back, and stomach. In time, these can progress to a condition that causes widespread skin peeling.
One key symptom of pemphigus is the positive Nikolsky sign. This is when you put a little pressure on the affected skin with a finger and the top layer of skin comes apart. This differentiates it from the tense blisters seen in a condition called pemphigoid, which don’t burst under light finger pressure.
Testing for Drug Induced Pemphigus
Pemphigus, a skin condition, is usually diagnosed by a doctor’s examination, but there are also tests like skin biopsies and serum analysis that can help confirm it. Patients with pemphigus may have a history of painful, soft, fluid-filled skin bumps or sores either on the skin or inside the mouth, which might have appeared after exposure to a certain drug. A small piece of skin can be removed and examined under a microscope to see if skin cells have separated above the bottom (basal) cell layer, which is a sign of pemphigus. Additionally, a type of blood test called an ELISA or an indirect immunofluorescent staining can be used to assess the presence of certain autoantibodies (anti-desmoglein 1 and 3), which are proteins produced by our immune system that mistakenly target and damage our own healthy tissues or cells, further confirming the diagnosis of pemphigus.
Treatment Options for Drug Induced Pemphigus
The primary way to treat pemphigus, an autoimmune disease, is to stop the use of the substance causing the condition, and then use medication to suppress or regulate the body’s immune response. Pemphigus can be life-threatening, so it needs to be treated quickly and aggressively. This usually involves a high dose of corticosteroids, which help reduce inflammation.
For serious cases, stronger medications known as immunosuppressants can also be used. These include drugs like azathioprine, mycophenolate mofetil, methotrexate, or cyclophosphamide. Another promising therapy is an antibody called rituximab, which can target and manage malfunctions in very specific immune cells, the B cells. However, some cases have shown a worsening of the disease after being treated with rituximab.
Despite ongoing research, there’s still not enough data from controlled clinical studies to define the best treatment approach for pemphigus caused by medication. What we currently know is that a combination of corticosteroids and an immunosuppressant like azathioprine often forms the core of the treatment.
What else can Drug Induced Pemphigus be?
There’s a range of autoimmune skin diseases that affect the proteins responsible for cell bonding in the skin and mucus linings. These conditions lead to skin sores that can be identified through various factors such as:
- The location and spread of skin sores
- The involvement of the mucus lining
- Microscopic examination of tissue samples from the sores
- Study of the immune response within the skin (immunopathology)
- Blood tests to detect antibodies
These conditions include:
- Pemphigus vulgaris
- Pemphigus vegetans
- Pemphigus foliaceus
- Bullous pemphigoid
- Herpes gestationis
- Mucous membrane pemphigoid
- Epidermolysis bullosa acquisita
- Linear IgA dermatosis
- Bullous lupus
- Dermatitis herpetiformis
What to expect with Drug Induced Pemphigus
Patients who have thiol-drug-induced pemphigus but don’t have cell surface autoantibodies typically have a positive outlook. If they stop taking the thiol-drug, around half of the patients usually improve.
However, many patients who got pemphigus due to a drug also have cell surface autoantibodies. This means their condition will likely follow a long-term course similar to pemphigus vulgaris, another type of this disease.
We don’t have exact death rates for drug-induced pemphigus, but there have been isolated cases of fatalities. Long-term pemphigus can greatly affect a patient’s well-being and quality of life. These patients often have extensive skin wounds that cause burning sensations and pain. If their mouths are affected, they may eat less, become dehydrated, and lose a significant amount of weight.
Possible Complications When Diagnosed with Drug Induced Pemphigus
Secondary infections caused by bacteria, skin ulcers, severe pain, gangrene, and poor cosmesis, are the common complications.
- Secondary bacterial infections
- Skin ulcers
- Sepsis
- Gangrene
- Severe pain
- Poor cosmesis
