What is Mycoplasma pneumoniae–Induced Rash and Mucositis (MIRM)?
Mycoplasma pneumoniae is a common germ that affects the lungs and can cause pneumonia. It is responsible for about 10% of all pneumonia cases. This number can even rise up to 37% among children in certain areas and studies. Usually, children and young adults are more commonly affected by this germ.
Besides causing lung problems, Mycoplasma pneumoniae can also cause other health problems that affect around 25% of patients. These can include cold-agglutinin hemolytic anemia, which affects red blood cells; arthritis, which affects the joints; pericarditis, which affects the bag-like structure around the heart; thrombosis or blood clots; and mucocutaneous manifestations, which are rashes that affect both the mucus membranes inside our body and our skin. These rashes can be triggered by a number of different things, including infections, reactions to medications and conditions where the body’s immune system attacks its own cells.
In the past, infections caused by Mycoplasma pneumoniae have been linked to rashes and other skin and mucus membrane issues. These have included conditions like urticaria, which is a type of hives or skin rash with red, raised, itchy bumps; erythema multiforme, which is a type of hypersensitivity reaction that occurs in response to medications, infections, or illness; Stevens-Johnson syndrome and toxic epidermal necrolysis, both of which are serious skin disorders that usually result from a reaction to medicine; and DRESS, which stands for Drug Reaction with Eosinophilia and Systemic Symptoms, another type of drug reaction.
However, classifying these rashes linked to Mycoplasma pneumoniae clearly has been difficult and has caused a lot of debates in medical literature. Recently, a certain type of rash related to Mycoplasma pneumoniae infections has been identified and given a name – Mycoplasma pneumoniae–Induced rash and mucositis. This term was coined by a scientist called Canavan in 2015 based on a review of various studies.
What Causes Mycoplasma pneumoniae–Induced Rash and Mucositis (MIRM)?
Infections from M pneumoniae, a type of bacteria, can lead to lung diseases and other conditions not related to the lungs, such as blood vessel inflammation, neurological problems, immune system disorders, blood clots, and changes in the skin and mucus membranes. Changes in the skin and mucus membranes happen in about 25% of people who have M pneumoniae infections.
In 2015, a new skin/mucus membrane condition related to M pneumoniae infections was identified and named MIRM. This was based on a review of 202 cases of people with M pneumoniae infections who had a rash (erythema multiforme), severe skin reactions (Stevens-Johnson syndrome), or inflammation of the mucus membranes without a rash.
MIRM is recognized by significant inflammation of mucus membranes. However, it usually involves less skin compared to other conditions that can come along with M pneumoniae infections, such as hives (urticaria), painful red bumps on the legs (erythema nodosum), rashes (erythema multiforme), serious skin reactions (Stevens-Johnson syndrome, TEN), or a hypersensitivity reaction that includes several severe symptoms (DRESS).
Risk Factors and Frequency for Mycoplasma pneumoniae–Induced Rash and Mucositis (MIRM)
M pneumoniae is a common cause of pneumonia, making up around 10% of such cases. This bacteria can also cause other health problems in about 25% of patients, including cold-agglutinin hemolytic anemia, arthritis, pericarditis, thrombosis, and skin conditions. A particular symptom of MIRM, which is a problem related to M pneumoniae, is the damage it can cause to the mucous membranes. This often shows up as ulcers and blisters in the mouth and genital regions and eye problems.
This disease most often affects children aged 5 and up. Some areas even report that this bacteria is the cause of pneumonia in 37% of children’s cases. Both M pneumoniae and MIRM usually show up during the colder months of the year. MIRM has been noted mainly in children and young adolescents, with the average age being 12. However, some studies have found MIRM cases in people aged 4 to 46, with the average age being 16. This condition has also been seen in young adults.
- In one study, 60% of MIRM cases were in males.
- 47% of patients had mucositis, an inflammation of the mucous membranes, without significant skin problems.
- 34% had mucositis without any skin problems at all.
Figuring out how many cases of MIRM there actually are is difficult for several reasons. For one, there isn’t a clear definition of MIRM, which makes it easy to confuse with other similar health issues. Additionally, underreporting can be an issue, as M pneumoniae often isn’t considered as the cause of illness during diagnosis. Limited resources for testing and failure to identify a definitive cause can also contribute to underreporting. Lack of a clear definition for MIRM led to inconsistent naming in scientific publications before 2015. Examples include “M pneumoniae–associated SJS”, “Fuchs syndrome”, “SJS without skin lesions”, and others.
Signs and Symptoms of Mycoplasma pneumoniae–Induced Rash and Mucositis (MIRM)
Gathering an in-depth understanding of a patient’s ongoing health issues is incredibly important. This can be key in telling apart Mycoplasma-induced Rash and Mucositis (MIRM) from other skin and mucus membrane conditions, such as erythema multiforme and Stevens-Johnson Syndrome (SJS)/ Toxis Epidermal Necrolysis (TEN). Before a MIRM rash appears, many patients often have symptoms like fever, cough, and general discomfort about a week earlier. People with SJS/TEN often show similar early symptoms, and they usually have a recent history of taking new medicines like antibiotics or anti-inflammatory drugs. This could make the cause of the condition harder to identify.
Patients with MIRM usually have physical symptoms that primarily involve rashes in areas like the mouth (94% of cases), eyes (82%), and genitals (63%). Patients could also have issues in the nostrils and anus. The rashes in these areas are usually painful and appear to be either ulcerated or bleeding. Nose issues can look like heavy, bloody crusts while anal issues can cause pain during bowel movements.
Non-mucosal rashes on the skin happen in about 47% of MIRM cases. If these rashes are not present, the condition is referred to as MIRM sine rash. If there is a rash, it’s often located in the extremities more so than on the trunk, and appears as a vesicle or blister in 77% of cases. Rashes that look like targets are seen in 48% of cases. Less usually, the rash can appear as small spots or widespread reddish bumps. The detached skin usually is less than 10% of the body surface area.
In contrast, erythema multiforme commonly starts on the extremities and then spreads to the face and trunk, and involves changing from small spots into small, hardened areas or spots with a bull’s eye appearance. Erythema multiforme minor involves little to no mucus membrane, and erythema multiforme major involves the appearance of a skin rash on one or more mucus membranes.
SJS/TEN starts off with a rash that includes small spots, purpura, widespread redness, bull’s eye appearance, and many soft, easy to rupture blisters. The blisters are usually centered and gradually spread out over the face and limbs. It usually extensively involves 2 or more mucus membrane sites. The extent of these skin conditions is determined by the amount of skin detachment. SJS involves less than 10% skin detachment while TEN involves more than 30% skin detachment. A skin detachment ranging from 10-30% could be either SJS or TEN.
Testing for Mycoplasma pneumoniae–Induced Rash and Mucositis (MIRM)
MIRM diagnosis involves checking for symptoms related to the lungs, which often resemble those of pneumonia. This can be confirmed through a physical check-up and possibly a chest X-ray. Your doctor may carry out lab tests to figure out the cause of the pneumonia, which could include detecting increased M pneumoniae IgM antibodies (these are a type of protein that the body produces when it’s fighting an infection), identifying the presence of M pneumoniae from throat or bullae (small, fluid-filled blisters) cultures, or locating serum cold agglutinins (proteins in your blood that can cause your red blood cells to clump together).
According to the definition provided by Canavan and others, diagnosing MIRM involves looking for the following features:
- Signs of atypical M pneumoniae pneumonia, such as fever, cough, abnormal lung sounds, or unusual findings on a chest X-ray.
- Lab results showing increased M pneumoniae IgM antibodies, the presence of M pneumoniae in throat or bullae cultures or detected by a method called PCR (a test to amplify and measure the amount of a specific type of DNA), and/or serial cold agglutinins.
- Skin peeling over less than 10% of the body.
- At least two mucosal sites (locations where mucous membranes are present like the mouth, eyes, or nose) showing signs of the disease.
- Occasional presence of vesiculobullous (blister-like) lesions or scattered irregular target lesions.
There are three types of MIRM based on the pattern of the skin rash that is not on mucous membrane areas:
- “Classic MIRM”: This type meets the above criteria and also has a specific type of skin rash. This can include vesiculobullous lesions, scattered target lesions, papules (small bumps), macules (flat, small discolored areas), and morbilliform eruptions (measles-like rash).
- “MIRM sine rash”: This type meets the criteria but doesn’t have a significant skin rash, although there could be a few quickly disappearing measles-like spots or a few blisters.
- “Severe MIRM”: This type meets the criteria, and there are symptoms in more than two mucous membrane locations. Also, there’s an extensive skin rash featuring widespread non-mucosal blisters or irregular target-like spots.
Treatment Options for Mycoplasma pneumoniae–Induced Rash and Mucositis (MIRM)
Determining whether a patient has MIRM, a type of skin and mucous membrane disorder, in urgent care situations can be tricky for healthcare providers. As such, it can be helpful for specialists, like infectious disease doctors or skin doctors (dermatologists), to take a look. If these resources are not available, the patient might need to be moved to a facility that has these resources.
For those diagnosed with MIRM, medical help typically involves controlling symptoms and managing complications. This can include pain relief for skin lesions and mouth sores, taking care of the affected mucous membranes, and addressing any dehydration or nutritional deficiencies brought about by an inability to eat or drink normally. Severely affected patients, typically those with extensive skin detachment akin to the effects of a burn, may need to be transferred to a burn center.
Patients with MIRM often have signs of atypical pneumonia. This means they might benefit from antibiotic treatments designed to fight various pathogens that can cause pneumonia. Generally, doctors recommend using antibiotics such as macrolides, tetracyclines, and fluoroquinolones, with macrolides usually being the first choice.
There are, however, increasing reports of macrolide resistance across the world, with varying levels of prevalence in different regions. For instance, resistance is most common in the Western Pacific and South East Asia, and least common in the East Mediterranean. As a result, doctors always need to be on their toes, especially when dealing with stubborn cases of Mycoplasma pneumoniae pneumonia, which may necessitate a change in the antibiotic regimen.
Some doctors also treat severe MIRM with corticosteroids and other medications to suppress the immune system. They may also administer intravenous immunoglobulin (IVIG), particularly in patients with severe mucositis, a painful inflammation of the mucous membranes. One study found that 35% of MIRM patients were given systemic corticosteroids and 8% received IVIG. Another, more recent review found that 77% of patients received antibiotics, 37% were treated with corticosteroids, and 11% received IVIG.
What else can Mycoplasma pneumoniae–Induced Rash and Mucositis (MIRM) be?
MIRM, or Mycoplasma Induced Rash and Mucositis, can be confused with other medical conditions that show similar symptoms on the skin and mucous membranes. Some of these include:
- Erythema multiforme major (a type of skin rash)
- SJS/TEN (serious skin disorders)
- DRESS (drug reaction causing skin symptoms)
- Staphylococcal scalded skin syndrome (a response to a bacterial infection)
- Hand-foot-and-mouth disease (common viral illness)
- Kawasaki disease (a rare children’s disease causing inflammation)
- Herpetic gingivostomatitis (infection causing blisters and inflammation in the mouth)
- Severe skin reactions like drug hypersensitivity syndrome
- Bullous systemic lupus erythematosus (a form of lupus affecting the skin)
- Plasma cell stomatitis (a rare condition causing painful mouth lesion)
- Diseases caused by Coxsackie virus and other enteroviruses
- SARS-CoV-2 infection (causing COVID-19)
- Autoimmune diseases, like Behçet disease and systemic lupus erythematosus
What to expect with Mycoplasma pneumoniae–Induced Rash and Mucositis (MIRM)
In general, people with MIRM (Myocardial Infarction with Nonobstructive Coronary Arteries) usually have a good outlook. Only a small portion (about 4%) of patients need to receive treatment in an intensive care unit, and many (around 81%) fully recover. However, around 8% of patients may experience a recurrence of MIRM.
On the other hand, patients with SJS/TEN, which are severe skin reactions (Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis), often require more frequent intensive care and have higher mortality rates than those with MIRM.
Possible Complications When Diagnosed with Mycoplasma pneumoniae–Induced Rash and Mucositis (MIRM)
While it’s true that about 81% of people with MIRM recover completely, there can be long-term problems. This mainly affects the inner lining (mucosa) of the body. About 9% of MIRM patients may experience damage to the lining of the eyes. This damage could lead to things like a reduction in the size of the lining of the eye (conjunctival shrinkage), corneal sores (ulcers), blindness, connections between the parts of the eye (ocular synechiae), and loss of eyelashes.
Changes in skin color (postinflammatory pigment changes) occurred in about 6% of patients. Unusual and significant connection of the mucosa in the mouth and genital area were seen in approximately 1% of patients. Occasionally, a patient may have complications such as persistent skin lesions, a reduction in a certain type of white blood cells (B-cell lymphopenia), limited lung disease, and long-term inflammatory lung disease (chronic obliterative bronchitis).
Even though death from MIRM is uncommon, experts think that most of the milder cases are not reported in medical studies. Thus, the actual rate of sickness and death could be much lower than what is reported.
Common Side Effects:
- Damage to the mucosa (inner lining of the body)
- Conjunctival shrinkage (reduction in the size of the lining of the eye)
- Corneal ulcers (sores on the cornea of the eye)
- Blindness
- Ocular synechiae (connections between the parts of the eye)
- Loss of eyelashes
- Changes in skin color
- Joining together of the lining in the mouth and genitals (mucosal synechiae)
- Persistent skin lesions
- B-cell lymphopenia (reduction in a certain type of white blood cells)
- Restricted lung disease
- Chronic obliterative bronchitis (long-term inflammatory lung disease)
- Potential death
Preventing Mycoplasma pneumoniae–Induced Rash and Mucositis (MIRM)
Patients who are found to have MIRM, a medical condition that can cause painful sores in the mouth, should be made aware that these sores could potentially make them become dehydrated and decrease their food intake. It is also key to keep skin sores clean in order to lessen the chances of getting another infection caused by bacteria.
How exactly MIRM spreads is not completely understood yet. However, it is recommended that patients who are suspected to have a lung infection caused by the bacteria known as M pneumoniae, as well as people who are close to them, use basic steps to stop the infection from spreading. They can do this by following droplet transmission precautions, which include measures to prevent the spread of diseases via droplets in the air produced when someone talks, coughs, or sneezes.
