Inclusion Body Myositis (IBM Inclusion Body Myositis) 4.25/5 (24)

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Definition

Inclusion body myositis (IBM) is an inflammatory muscle disease (myositis) which, for unknown reasons, attacks older people and develops gradually. IBM was described as a separate disease for the first time in 1978 (Carpenter, S, 1978). Thigh muscles and finger flexors (hand grip) are among the muscles that weaken. A tissue sample from muscle is crucial for the diagnosis. There are no good drugs against this type of myositis (reference: McLeish E, 2022). IBM is considered part of the myositis diseases. These can be divided into five groups (Glaubitz S, 2020). 1) Polymyositis (PM), 2) Dermatomyositis (DM) (muscle and skin affection), 3) Immune-mediated necrotizing myopathy (IMNM), including statin-induced myopathy, 4) Antisynthetase syndrome (lungs are attacked and special results in myositis-specific antibody exists) and 5) Inclusion body myositis (IBM).

Occurrence

In Norway, it has been found that 3,3/100.000 have inclusion body myositis (prevalence) (ref. Dobloug C, 2015).. The disease is thus defined as a rare disease. Men are attacked somewhat more often than women. Usual age at diagnosis is 50-70 years (reference; Molberg Ø, 2016).

There is a very rare form of the disease that differs from typical IBM in particular in that it attacks teenagers and young adults (Broccolini A, 2014). This hereditary (familial/genetic) IBM (hIBM) also has a familial occurrence (Ranque-Francois B, 2005). hIBM is also called "Distal myopathy with rimmed vacuoles" and is a genetic disease. This form is not discussed in more detail here.

Classic IBM is also called sporadic inclusion body myositis and is considered one of the most common muscle diseases in people over 50 (reference: dand Paepe B, 2018).

Symptoms

Inclusion Body-myositis
Inclusion body myositis. Muscle atrophy (thin muscles) in forearms and thighs. Tissue sample with «rimmed vacuole» Illustration: Turner MR, Talbot K - Pract Neurol (2013). . CC BY NC 3.0

Because the symptoms develop slowly, it often takes 5-6 years before a final diagnosis is made (reference: Dobloug GC, 2014).

The thigh muscles gradually weakens so that one has problems getting up from squatting and eventually from the chair. Difficulty climbing stairs is also common.

Forearms, fingers and feet. Muscles in the forearms and calves often become thinner and weaker over time. Hand strength (hand pressure) weakens and walking function is affected with an increased tendency to fall.

asymmetry. The weakness does not have to be the same in both halves of the body (asymmetrical affection), although the changes are expected on both sides during the course.

Swallowing muscles. Some people experience reduced swallowing muscle function and swallowing problems (dysphagia). This can cause food to enter the lungs (aspiration) and cause pneumonia.

Polyneuropathy is marked by increasing numbness and numbness, most often in the feet and hands.

Examinations

Inclusion body myositis eventually has typical characteristics, but they are difficult to determine early in the course of the disease.

Medical history maps current symptoms (see above) with an emphasis on the development of failure in the forearms, hands, calves and feet, but also in the thigh muscles. Swallowing problems are requested. Some suffer from muscle pain and numbness (polyneuropathy).

Clinical examination observe muscle size in legs and arms. Thin arms and legs (distal muscle atrophy) can be seen (illustration above). Muscle strength is assessed: Walking on heels and toes can be difficult, and it can be problematic to get up from squatting or from a chair without support. and weakness: Finger flexors, grasping function (most often non-dominant hand). The fingers may be bent (flexed position). - Physiotherapists can use standardized tests for muscle strength, which can be important tools in the follow-up, especially to assess possible disease development over time or whether treatment goals are achieved. Physiotherapists test both direct muscle strength and endurance.

Blood tests often shows that creatine kinase (CK) is increased to 2-5 times the upper normal value. Other tests are taken too far to exclude other conditions and include CRP, SR, white blood cells (leukocytes with differential counts), platelets (thrombocytes), electrolytes, liver, kidney and thyroid function tests, glucose. 

No classics antibodies expected to exist. Anti-cytosolic 5′-nucleotidase 1A (cN-1A) has in a study shown a sensitivity (ability to capture IBM) of 50% (Felice KJ, 2018), but in other cohorts somewhat lower, approx. 30%. Unfortunately, the antibody is not specific for IBM and is also seen in other conditions, even without muscle manifestations (Lloyd TE, 2016). cN-1A is available for analysis (blot) among myositis-specific antibody.

EMG/neurography may show myopathy changes

Imaging. includes MRI of muscles, most often thigh muscles. Changes that are quite characteristic (Reference: Tasca G, 2015). One sees a clear loss of muscle mass (atrophy) and fat infiltration. Typical localization is on the stretch side of the thigh muscles, especially the quadriceps muscles near the knee (distal on the thigh). Often a gradient with increasing changes closest to the knee. The sartorius muscles are also often attacked, while the recutus femoris muscle is not attacked in everyone. Muscles behind the thigh (flexor muscles) attack more variably and may be normal. X-ray of esophagus shows reduced swallowing function in approx. 60%. Ultrasound examination of muscles can show the same distribution of atrophy as with MRI (reference: Leeuwenberg KE, 2020).

Tissue sample (biopsy) is often decisive for the diagnosis. One sees both so-called "degenerative and inflammatory features" with endomyseal invasion by CD8+ lymphocytes, cytoplasmic and intranuclear inclusions. Amyloid in muscle fibers (crystal violet staining) ("Alzheimer in the muscles"). Light microscopy: Vacuoles, intra-nuclear and intra-cytoplasmic inclusions. Electron microscopy: Microtubular filaments in the inclusions. These are stained with Congo red, thioflavin and crystal violet (indicating amyloidosis) (reference: Tasca G, 2015). Typical findings at biopsy are thus vacuoles ("rimmed vacuoles", "inclusion bodies"), endomyseal inflammation, intracellular amyloid depots and tubulofilaments.

Diagnosis

For the diagnosis, medical history, age at onset, course of the disease and examinations are decisive (see above). One can also use diagnostic criteria:

Diagnostic criteria

Adapted from "The ENMC IBM research diagnostic criteria 2011" (Rose MR. 2011). Specificity 99%, sensitivity 57%.

Clinic and laboratoryClassificationPathological findings
Duration > 12 months. Age at onset > 45 years. Knee extension weaker than hip flexion and/or finger flexion weakness > shoulder abduction weakness. CK not higher than 15× upper reference limitClinic‐pathologically defined IBMAll of the following: Endomyseal inflammatory infiltrates- Rimmed vacuoles (inclusion bodies) Protein accumulation a or 15‐ to 18‐nm filaments
Duration > 12 months. Age at onset > 45 years. Knee extension weaker than hip flexion and/or finger flexion weakness > shoulder abduction weakness. CK not higher than 15× upper reference limitLikely / possible IBMOne or more, but not all, of the following: Endomyseal inflammatory infiltrates. Rimmed vacuoles (inclusion bodies). Protein accumulation a or 15‐ to 18‐nm filaments  
a amyloid or other protein accumulations by established method (for example for amyloid Congo red, crystal violet, thioflavin T/S, for other proteins p62, SMI‐31, TDP‐43).

Similar conditions / differential diagnoses

Treatment

All are recommended physiotherapy, occupational therapy and personal training to reduce the risk of falls and injuries, as well as psychological support. Physical training can improve mitochondrial function (the cells' powerhouse), blood circulation, muscle growth and reduce muscle inflammation. Adapted diet For good nutrition, optimal body weight is emphasized, but there are no special supplements that have been shown to influence the course of the disease.

In case of swallowing problems (dysphagia), the need for pharyngo-oesophageal dilatation or crico-pharyngeal myotomy is assessed (Oh TH, 2008).

Medicines unfortunately have little or no effect and side effects can outweigh the benefit, but response to treatment differs from person to person. Sometimes a trial of treatment is made over 6 months. In that case, the disease is mapped and treatment goals are outlined in advance. After assessing the effect, it is assessed whether further drug treatment is appropriate. If treatment attempts with immunosuppressive drugs are made, the dosage is individual. A regime that has been used is: Prednisone 0,5-1mg/kg/day the first week, then reduction so that the dose is 10mg/d after a few weeks. This dose is maintained for up to 6 months. One must be aware that there is generally an uncertain effect of corticosteroids, even if the CK values ​​improve. Prednisolone is often combined with Methotrexate 7,5mg - 25mg /week over 3 - 6 months or Imurel 1,5 – 2,5 mg/day. If no effect on muscle strength and progression after 6 months, one should consider ending the treatment. There is no safe effect of Sendoxan, Leukeran, azathioprine (Imurel), Ciclosporin A) or methotrexate in most people.

Intravenous immunoglobulin (IVIG, Oktagam) can be tried in case of severe affection of the esophagus and swallowing difficulties (reference: Cherin, P, Pelletier, S, Neurology 2002). Some may have a temporary effect on swallowing difficulties (Dobloug C, 2012), but in general the treatment effect of IVIG is not well documented (Glaubitz S, 2020). Trials of new drugs are ongoing for IBM (Naddaf E, 2018).

Prognosis

The disease is not fatal, but entails an increasing need for aids. The course is individual and probably also depends on whether training and other measures are carried out. On average, one manages without walking aids for 7,5-10 years from the onset of symptoms. Then, for example, poles or canes are used. After 13-15 years, most will need transport in a wheelchair (Greenberg SA, 2019).

Guidelines

Lundberg IE, 2017: EULAR Classification of myositis 

Norwegian Rheumatological Association

Literature


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