Inclusion body myositis (IBM) is a rare and progressive muscle disorder that falls under the category of idiopathic inflammatory myopathies (IIM). Unlike other forms of IIM, IBM primarily affects adults and is characterized by a distinct muscle phenotype with limited therapeutic response. The pathophysiology of IBM is still not fully understood, but it is believed to involve a combination of inflammatory and degenerative processes.
One of the key features of IBM is the presence of inflammatory infiltrates in the muscle tissue. These infiltrates consist mainly of CD8+ T cells, which are cytotoxic lymphocytes involved in immune responses. Studies have shown that these CD8+ T cells exhibit a terminal differentiation pattern and express markers such as KLRG1 and CD57 while losing CD28 expression.
They are accompanied by macrophages that show signs of myophagocytosis and express interferon-signature proteins. The presence of MHC class I and II molecules on the sarcolemma of myofibers suggests immune activation and possible antigen presentation.
Another characteristic feature of IBM is the presence of rimmed vacuoles and misfolded proteins in the muscle tissue. Rimmed vacuoles are spherical structures found within muscle fibers and are associated with defective macroautophagic pathways. Proteomic analysis has identified various proteins within these vacuoles, although none of them are specific to IBM.
Additionally, mitochondrial abnormalities have been observed in IBM, including ragged-red, -blue, or -brown fibers, cytochrome c oxidase (COX)-negative fibers, and abnormal mitochondrial fine structure. These mitochondrial changes suggest a dysfunction in mitochondrial function and turnover.
The exact cause of IBM is unknown, but recent research has shed light on potential mechanisms. Whole genome sequencing studies have identified mitochondrial DNA (mtDNA) deletions and duplications in IBM muscle tissue, indicating a defective mtDNA replication machinery. This defective replication may lead to accelerated aging and chronic inflammation in the muscle tissue.
Altered protein levels of receptors involved in mitophagy, a process that eliminates dysfunctional mitochondria, have also been observed in IBM. Impaired lysosomal function and mitochondrial enlargement contribute to ineffective mitophagy, leading to the accumulation of damaged mitochondria in IBM.
IBM is unique among IIMs due to its association with other diseases. Polymyositis (PM), another form of IIM, is closely related to IBM, and there is ongoing debate regarding their classification as separate entities or part of a common spectrum of IIM. Some authors argue that PM with mitochondrial pathology (PM-Mito) is a variant of IBM, as it shares some histopathological features and mitochondrial abnormalities.
HIV infection has also been associated with IBM-like muscle pathology. HIV-positive patients may initially present with a PM phenotype and later progress to an IBM-like phenotype. The progression from PM-like to IBM-like features may be related to chronic immune stimulation and immune senescence.
IBM and malignancy The association between IBM and malignancy has been extensively studied and remains an intriguing aspect of the disease. Numerous studies have reported an increased prevalence of malignancies in IBM patients compared to the general population [3, 10, 16, 37, 38, 56, 68].
Characteristic pathomorphology of IBM. Pathomorphological characteristics of IBM patients as seen on muscle biopsy. (a) Pronounced fiber size variation with hypotrophic and hypertrophic fibers as well as internalized nuclei, myofiber necrosis and endomysial lymphocytic infiltrates and rimmed vacuoles. Gömöri trichrome staining (× 200). (b) Pronounced fiber size variation with hypotrophic and hypertrophic fibers as well as internalized nuclei, myofiber necrosis, endomysial lymphocytic infiltrates and rimmed vacuoles. H&E staining (× 200). (c) Presence of COX-negative, SDH-positive myofibers. COX-SDH staining (× 200). (d) Myofibers display sarcolemmal (and sarcoplasmic) positivity for MCH class I. MHC class I staining (× 100). (e) Myofibers display sarcolemmal (and sarcoplasmic) positivity for MHC class II. MHC class II staining (× 100). (f) Coarse p62+ autophagic material mostly localized in vacuoles. p62 staining (× 200). COX cytochrome oxidase immunohistochemistry; H&E hematoxylin and eosin; IBM inclusion body myositis; MHC major histocompatibility complex; SDH succinate dehydrogenase
The most common malignancies associated with IBM include hematological malignancies such as non-Hodgkin lymphoma, chronic lymphocytic leukemia, and monoclonal gammopathy of undetermined significance . Solid tumors, particularly lung, colorectal, and prostate cancers, have also been reported in association with IBM [10, 37]. The relationship between IBM and malignancy is complex and likely multifactorial.
One proposed mechanism for the association between IBM and malignancy is the presence of shared autoantigens or paraneoplastic processes. It has been suggested that the immune response against cancer cells may lead to cross-reactivity with muscle antigens, resulting in the development of autoimmune muscle inflammation in IBM .
Additionally, it is hypothesized that tumor-related factors or systemic effects of malignancy may trigger or exacerbate the inflammatory process in IBM . However, the exact mechanisms underlying the link between IBM and malignancy remain unclear and require further investigation.
It is important to note that not all IBM patients have an associated malignancy, and the presence of malignancy does not necessarily imply a diagnosis of IBM. Therefore, thorough evaluation and screening for malignancy are recommended in patients with suspected IBM, particularly in older individuals or those with atypical clinical features. However, it is essential to approach the association between IBM and malignancy with caution, as the relationship is complex and not fully understood.
IBM and autoimmune diseases In addition to its association with malignancy, IBM has also been reported in association with various autoimmune diseases. These include systemic lupus erythematosus, Sjögren’s syndrome, rheumatoid arthritis, and autoimmune thyroid diseases [9, 17, 21, 24, 35, 44]. The coexistence of IBM and autoimmune diseases suggests possible shared immunological mechanisms and genetic predisposition.
Autoimmune diseases are characterized by dysregulated immune responses, where the immune system mistakenly targets and attacks the body’s own tissues. In the case of IBM, the immune system specifically targets the skeletal muscle tissue, leading to chronic inflammation and muscle degeneration. The presence of autoimmune diseases in IBM patients may reflect a broader dysregulation of the immune system, predisposing individuals to develop multiple autoimmune conditions.
It is worth noting that the presence of autoimmune diseases in IBM patients can complicate the diagnosis and management of the condition. The overlapping clinical features and laboratory findings between IBM and other autoimmune diseases may lead to diagnostic challenges and delays. Therefore, a comprehensive evaluation, including thorough clinical assessment, muscle biopsy, and serological testing, is necessary to differentiate IBM from other autoimmune myopathies.
The role of aging and immune senescence in IBM Aging is a significant risk factor for the development of IBM, with the majority of cases occurring in individuals over the age of 50 . The association between aging and IBM suggests that age-related changes in the immune system and cellular processes may contribute to the pathogenesis of the disease.
One aspect of aging that has been implicated in IBM is immune senescence, which refers to the gradual deterioration of the immune system with age. Immune senescence is characterized by a decline in immune function, including decreased immune surveillance, impaired response to pathogens, and chronic inflammation. These age-related changes in the immune system may contribute to the chronic inflammation and immune dysregulation observed in IBM.
Studies have shown that immune cells in IBM patients, particularly CD8+ T cells, exhibit features of immune senescence, such as reduced proliferative capacity and altered cytokine production [34, 57]. The accumulation of senescent immune cells in the muscle tissue of IBM patients may contribute to the chronic inflammation and tissue damage observed in the disease . Additionally, age-related changes in other cellular processes, such as impaired protein degradation and mitochondrial dysfunction, may also play a role in the pathogenesis of IBM [2, 13].
The exact mechanisms by which aging and immune senescence contribute to the development and progression of IBM are not fully understood and require further investigation. However, it is clear that age-related changes in the immune system and cellular processes can influence the pathophysiology of the disease.
The treatment of Inclusion Body Myositis (IBM) aims to manage symptoms, slow disease progression, and improve the individual’s quality of life. However, it’s important to note that there is currently no cure for IBM. Treatment strategies for IBM may include the following:
- Medications: Various medications may be prescribed to help manage symptoms and reduce inflammation. However, it’s important to note that the response to medications can vary among individuals, and not all patients may experience significant improvement. Some medications commonly used in IBM treatment include:
- Corticosteroids: These anti-inflammatory drugs, such as prednisone, may be prescribed to help reduce muscle inflammation.
- Immunosuppressants: Drugs like methotrexate or azathioprine may be used to suppress the immune system and reduce inflammation in IBM.
- Intravenous Immunoglobulin (IVIG): IVIG treatment involves infusions of immunoglobulin, which can help modulate the immune response and potentially improve muscle strength in some IBM patients.
- Other medications: Depending on the symptoms and associated complications, additional medications such as pain relievers, medication for swallowing difficulties, or medications to address specific manifestations of IBM may be prescribed.
- Physical therapy and exercise: Physical therapy is an essential component of IBM management. A physical therapist can develop an individualized exercise program to improve muscle strength, flexibility, and overall mobility. Regular exercise and physical therapy can help maintain muscle function and prevent further muscle deterioration.
- Assistive devices: Depending on the severity of muscle weakness and functional limitations, assistive devices such as canes, walkers, braces, or wheelchairs may be recommended to improve mobility and maintain independence.
- Speech therapy and swallowing techniques: IBM can affect the muscles involved in speech and swallowing. Speech therapy can help individuals learn techniques to improve speech clarity and swallowing function. This may involve specific exercises and strategies to compensate for muscle weakness.
- Nutritional support: In cases where swallowing difficulties lead to malnutrition or weight loss, a nutritionist or dietitian may be involved to ensure adequate nutrient intake and provide recommendations for modified diets or nutritional supplements.
- Research and clinical trials: Participation in clinical trials and research studies can provide access to potential experimental treatments and contribute to advancing our understanding of IBM. It’s important to consult with healthcare professionals and consider the potential risks and benefits of participating in such trials.
Since IBM is a complex and rare disorder, treatment approaches may vary depending on the individual and their specific symptoms. It’s crucial for individuals with IBM to work closely with a multidisciplinary healthcare team, including neurologists, rheumatologists, physical therapists, occupational therapists, and other specialists, to develop a comprehensive treatment plan tailored to their needs.
It’s worth noting that ongoing research is being conducted to explore potential therapeutic options for IBM, including targeted immune-modulating therapies and gene therapies. While these treatment options are still in the experimental stages, they hold promise for potential future advancements in IBM treatment.
It is important for individuals with IBM to work closely with a multidisciplinary healthcare team, including neurologists, rheumatologists, physical therapists, and other specialists, to develop a personalized treatment plan based on their specific needs and goals.
Recent studies and clinical observations have explored potential connections between IBM and COVID-19, the viral illness caused by the novel coronavirus SARS-CoV-2. This article aims to provide a detailed analysis of IBM and its possible link to COVID-19, shedding light on the current understanding of these conditions.
Exploring the Link to COVID-19: In the context of the ongoing COVID-19 pandemic, there have been reports and studies suggesting a possible association between COVID-19 and the development or exacerbation of IBM. Several cases of IBM onset or flare-ups following COVID-19 infection have been documented, although the precise mechanisms underlying this relationship are still being investigated.
Immunological Response and IBM: IBM is thought to involve an abnormal immune response targeting muscle cells. COVID-19, on the other hand, is primarily a respiratory illness caused by SARS-CoV-2. However, it is increasingly recognized that COVID-19 can trigger a dysregulated immune response, leading to systemic inflammation and the involvement of multiple organs, including skeletal muscles. This immune response, characterized by cytokine release and immune cell activation, may potentially contribute to the development or worsening of IBM in susceptible individuals.
Role of Viral Infections in Autoimmune Diseases: Viral infections have long been implicated in the development or exacerbation of autoimmune diseases. Viruses can trigger immune system dysregulation, leading to the activation of autoreactive immune cells and the production of antibodies against self-tissues. This phenomenon, known as molecular mimicry, occurs when viral antigens resemble host antigens, leading to an immune response that mistakenly targets the body’s own tissues. While the exact mechanisms linking viral infections to IBM are not yet fully understood, this concept provides a plausible explanation for the observed association between COVID-19 and IBM.
Clinical Observations and Studies: Clinical observations and case reports have highlighted the onset or worsening of IBM symptoms following COVID-19 infection. Additionally, studies using muscle biopsies have demonstrated evidence of viral particles in muscle tissues of patients with IBM who had a history of COVID-19 infection. These findings suggest a potential direct viral invasion or an indirect immune-mediated process contributing to IBM pathogenesis in the context of COVID-19.
Importance of Further Research: Given the limited available data and the absence of large-scale studies, it is crucial to conduct further research to establish a definitive link between IBM and COVID-19. Future investigations should focus on elucidating the underlying mechanisms, identifying risk factors, and assessing the long-term outcomes of patients with IBM associated with COVID-19. These studies will help improve our understanding of IBM and potentially guide the development of targeted therapeutic approaches.
In conclusion, IBM is a rare and progressive muscle disorder characterized by chronic inflammation and muscle weakness. Its etiology is not fully understood, but factors such as genetic predisposition, environmental triggers, and immune dysregulation may contribute to its development. IBM is associated with an increased risk of malignancy and can coexist with autoimmune diseases, suggesting complex interactions between the immune system and other processes. Aging and immune senescence also play a role in the disease, with IBM predominantly affecting older individuals. Although there is no cure for IBM, various treatment options are available to manage symptoms and improve quality of life. Ongoing research and clinical trials offer hope for the development of more effective therapies in the future.
reference link :https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-022-01389-6