Inclusion Body Myositis

What is Inclusion Body Myositis?

Inclusion body myositis (IBM) is the most common type of autoimmune myositis, a condition where the body’s immune system mistakenly attacks its own muscles, in people over 50 years old. Several guidelines have been created to help doctors diagnose IBM, but these are not always fully accurate or sensitive. The European Neuromuscular Centre (ENMC) in 2011 developed a specific set of criteria for diagnosing IBM that is highly accurate (more than 99% specificity), but it does not pick up all cases (57% sensitivity).

The ENMC 2011 criteria for diagnosing IBM are as follows:

Essential Features:

The condition started after age 45
Symptoms have been present for over a year
Levels of a muscle enzyme called creatine kinase are not more than 15 times the normal limit

Clinical Features:

Weakness in the thigh muscles (quadriceps) is greater than in the hip flexor muscles
Weakness in the finger flexors is greater than in the muscles that lift the arm at the shoulder (shoulder abductors)

Pathological Features:

Inflammation within the muscle tissue (endomysial inflammatory infiltrate)
Oval-shaped clear areas within the cells (rimmed vacuoles)
Build-up of proteins or certain types of fibres within the cells
Increased levels of a protein called MHC class I

There are three main types of IBM diagnosed based on these criteria:

Clinicopathologically defined IBM: All essential criteria are met, plus one or both clinical criteria, and the first three pathological criteria
Clinically defined IBM: All essential and clinical criteria are met, plus one or more but not all pathological criteria
Probable IBM: All essential criteria are met, plus one clinical criterion, and one or more but not all pathological criteria

What Causes Inclusion Body Myositis?

Inclusion body myositis is typically an isolated condition, which means it happens randomly without a clear reason (also called sporadic inclusion body myositis, or sIBM). However, in some rare instances, it can be inherited from family members (referred to as hereditary inclusion body myositis, or hIBM).

Risk Factors and Frequency for Inclusion Body Myositis

Inclusion body myositis (IBM) affects approximately 5 to 9 out of every million adults. Its occurrence can change based on location, ethnicity, and age. This variation might be because of differences in how often it’s diagnosed or reported in different places and among different ethnic groups. Unlike many diseases where the immune system attacks the body’s own cells, IBM is more likely to affect males than females. The ratio is around 3 males for every female affected.

Signs and Symptoms of Inclusion Body Myositis

Inflammatory myopathy, specifically Inclusion Body Myositis (IBM), is a condition with symptoms that may vary from person to person. The most common sign is a gradual onset of muscle weakness, which worsens over time. Here are some ways this muscle weakness might be noticeable in day-to-day activities:

Difficulty in climbing stairs or getting up from a chair due to pelvic girdle weakness
Walking slowly due to weakness in the hip flexors
Frequent falls because of weak quadriceps, leading to buckling knees
Tripping often due to weak ankle dorsiflexion, known as foot drop
Struggling to comb hair or reach items in overhead cabinets because of shoulder girdle weakness
Reduction in grip strength due to weakening finger flexors
Difficulty lifting the head from a pillow due to neck muscle weakness

IBM is distinct from other types of inflammatory myopathies, as it demonstrates some specific features:

The disease usually affects the wrist or finger flexors and foot extensors unevenly and more towards the end of the limbs
The disease onset is insidious, meaning it progresses slowly and gradually. It often takes an average of 5 years before the disease is diagnosed
IBM causes muscle wasting, specifically in the finger flexors, wrist flexors, and quadriceps. This wasting, or atrophy, accompanies weakness and becomes more pronounced as the disease progresses. Unlike other inflammatory myositis conditions, this muscle wasting can even be present during initial evaluations in IBM

About 30% to 50% of IBM patients experience difficulty in swallowing, known as dysphagia. This can lead to nasal regurgitation of liquids and risk of inhaling food or liquid into the lungs. Weakness in the throat muscles can also result in a weak voice or dysphonia.

During a physical examination, a healthcare provider will assess the distribution of muscle weakness and atrophy. In IBM, the most telling signs are typically weakness and wasting of the thigh muscles (quadriceps) and forearm flexors. An early symptom can be weakness in the distal finger flexor, which can be tested by assessing the bending at the last joint of the fingers.

Testing for Inclusion Body Myositis

If your doctor suspects that you’re suffering from inclusion body myositis, which is a condition causing muscle weakness, an in-depth health history, and a thorough physical examination will be the first steps in assessing your situation.

Your doctor will likely order several laboratory tests, including a serum creatinine kinase test to check your muscle health. This test is often elevated in patients with muscle damage. More tests may also be done to check for other markers of muscle damage, such as Aldolase, LDH, ALT, and AST.

Inflamed tissues usually increase the counts of ESR and CRP in your blood. However, with inclusion body myositis, these levels can be normal. Your doctor may also look for the presence of Mup44 antibodies, which are common in this condition. Still, they can also be detected in patients with immune diseases like lupus and Sjogren syndrome even without muscle illness.

Electromyography (EMG), which measures muscle response or electrical activity, can play a part in diagnosing inclusion body myositis by differentiating muscle weakness caused by the disease from weakness caused by nerve disorders. An EMG typically shows specific characteristics like irritated muscle fibers and changes in motor unit potentials (a measure of nerve to muscle communication) during muscle contractions in patients with myositis.

Magnetic Resonance Imaging (MRI) can also be useful in visualizing large chunks of muscle to observe inflammation, fatty changes, muscle wasting, and presence of fluid. This can be particularly useful in distinguishing current active disease from old damage in patients with inclusion body myositis.

Both these techniques, EMG and MRI, are also helpful in guiding the doctor about which muscle to biopsy. The ideal muscle for biopsy is one that still has active disease but has not yet reached advanced or end-stage disease.

When a biopsy is performed, the tissue is examined for certain hallmarks of inclusion body myositis. In nine out of ten cases, distinct changes in the muscle fibers could be seen along with inflammatory cells infiltrating the muscles.

It’s also worth noting that inclusion body myositis may associate with autoimmune diseases such as Sjogren syndrome and sarcoidosis, lymphatic system cancers, and infections such as HIV and Hepatitis B. Therefore, your doctor may recommend screening tests for these as well.

Treatment Options for Inclusion Body Myositis

There’s no specific drug treatment that has been shown to be effective for a rare muscle disorder called sporadic inclusion body myositis. Treatments have included various drugs like corticosteroids, methotrexate, cyclophosphamide, azathioprine, IVIG (intravenously administered immunoglobulin), and alemtuzumab. Alemtuzumab has been shown in a pilot study to reduce certain key indicators related to the disease, such as IL 1 beta and Class I MHC complex.

In a small trial, a drug called bimagrumab, which is an antibody against type II activin receptors, showed an increase in muscle volume after 8 weeks of treatment. Anakinra, which blocks an inflammatory molecule called IL-1, has shown promising results in small case studies and individual reports. There are also ongoing trials with gene therapy using a molecule called follistatin and other drugs like arimoclomol and natalizumab.

Patients who are more likely to respond to these treatments include those with very elevated levels of an enzyme called serum CK (more than 5 times the upper norm), those showing active inflammation in imaging studies or biopsies, the presence of autoantibodies associated with myositis (an inflammation of the muscles), and those with other overlapping connective tissue diseases.

For those suffering severe difficulty swallowing, a condition known as dysphagia, that doesn’t improve with drugs and IVIG, surgical interventions like cricopharyngeal dilation or myotomy may be considered. For extremely severe cases, a feeding tube, also known as a gastrostomy tube, may need to be inserted.

Physical therapy and rehabilitation play an important role in the overall treatment plan for dealing with this condition. Exercise can help to increase muscle strength and improve quality of life. Graduated rehabilitation led by a trained physiatrist (a doctor who specializes in physical medicine and rehabilitation) should be started as soon as possible for best results. Occupational therapy can also prove helpful by teaching techniques to adjust to social and professional life.

While it’s not yet proven by clinical evidence, some doctors recommend daily supplementation with creatine monohydrate, a substance that may enhance muscle function.

Anakinra, the IL-1 blocker mentioned earlier, was experimented with in case reports and a small series of patients, and some of them posted positive results.

Here are some medical conditions that relate to muscle weakness or nerve disorders:

Acid maltase deficiency
Chronic inflammatory demyelinating polyradiculoneuropathy
Drug-induced myocarditis
Emergent management of myasthenia gravis
Hereditary inclusion body myopathy
Late-onset distal myopathies
Motor neuron disease
Myofibrillar myopathies
Overlap myositis
Post-polio syndrome

Frequently asked questions

Inclusion Body Myositis (IBM) is the most common type of autoimmune myositis, where the body's immune system mistakenly attacks its own muscles, typically in people over 50 years old.

Inclusion Body Myositis affects approximately 5 to 9 out of every million adults.

The signs and symptoms of Inclusion Body Myositis (IBM) include: - Gradual onset of muscle weakness, which worsens over time - Difficulty in climbing stairs or getting up from a chair due to pelvic girdle weakness - Walking slowly due to weakness in the hip flexors - Frequent falls because of weak quadriceps, leading to buckling knees - Tripping often due to weak ankle dorsiflexion, known as foot drop - Struggling to comb hair or reach items in overhead cabinets because of shoulder girdle weakness - Reduction in grip strength due to weakening finger flexors - Difficulty lifting the head from a pillow due to neck muscle weakness - The disease usually affects the wrist or finger flexors and foot extensors unevenly and more towards the end of the limbs - The disease onset is insidious, progressing slowly and gradually, often taking an average of 5 years before diagnosis - IBM causes muscle wasting, specifically in the finger flexors, wrist flexors, and quadriceps, which accompanies weakness and becomes more pronounced as the disease progresses - About 30% to 50% of IBM patients experience difficulty in swallowing, known as dysphagia, which can lead to nasal regurgitation of liquids and risk of inhaling food or liquid into the lungs - Weakness in the throat muscles can result in a weak voice or dysphonia - During a physical examination, healthcare providers will assess the distribution of muscle weakness and atrophy, with the most telling signs being weakness and wasting of the thigh muscles (quadriceps) and forearm flexors. An early symptom can be weakness in the distal finger flexor.

Inclusion Body Myositis can be either sporadic (randomly occurring without a clear reason) or hereditary (inherited from family members).

The doctor needs to rule out the following conditions when diagnosing Inclusion Body Myositis: - Acid maltase deficiency - Chronic inflammatory demyelinating polyradiculoneuropathy - Drug-induced myocarditis - Emergent management of myasthenia gravis - Hereditary inclusion body myopathy - Late-onset distal myopathies - Motor neuron disease - Myofibrillar myopathies - Overlap myositis - Post-polio syndrome

The types of tests that may be needed for the diagnosis of Inclusion Body Myositis include: 1. Serum creatinine kinase test: This test checks the health of the muscles and is often elevated in patients with muscle damage. 2. Additional laboratory tests: These may include tests for other markers of muscle damage such as Aldolase, LDH, ALT, and AST. 3. ESR and CRP tests: These tests measure inflammation in the body, although levels may be normal in Inclusion Body Myositis. 4. Mup44 antibody test: This test can help identify the presence of antibodies common in Inclusion Body Myositis, although they can also be found in other immune diseases. 5. Electromyography (EMG): This test measures muscle response or electrical activity and can differentiate muscle weakness caused by the disease from weakness caused by nerve disorders. 6. Magnetic Resonance Imaging (MRI): This imaging technique can visualize muscle inflammation, fatty changes, muscle wasting, and the presence of fluid. 7. Muscle biopsy: A biopsy of muscle tissue can be examined for specific hallmarks of Inclusion Body Myositis, such as changes in muscle fibers and inflammatory cells. 8. Screening tests: Depending on the patient's medical history, the doctor may recommend screening tests for autoimmune diseases, lymphatic system cancers, and infections such as HIV and Hepatitis B.

There is no specific drug treatment that has been shown to be effective for sporadic inclusion body myositis. However, various drugs have been used in treatment, including corticosteroids, methotrexate, cyclophosphamide, azathioprine, IVIG, and alemtuzumab. Alemtuzumab has shown promise in reducing certain key indicators related to the disease. Other potential treatments being explored include bimagrumab, anakinra, gene therapy using follistatin, and drugs like arimoclomol and natalizumab. Patients who are more likely to respond to these treatments are those with elevated levels of serum CK, active inflammation, presence of autoantibodies associated with myositis, and overlapping connective tissue diseases. Physical therapy, rehabilitation, and occupational therapy are also important components of the overall treatment plan. Some doctors may recommend daily supplementation with creatine monohydrate, although this has not been proven by clinical evidence.

The text does not mention any specific side effects when treating Inclusion Body Myositis.

The text does not provide information about the prognosis for Inclusion Body Myositis.

A healthcare provider or a doctor who specializes in physical medicine and rehabilitation (physiatrist).

Joint Muscle and Bone Muscle Weakness