Dermatomyositis (DM) is an idiopathic inflammatory myopathy with cutaneous and systemic manifestations influenced by autoantibody profiles. We report a rare case of anti-nuclear matrix protein 2 (anti-NXP2)-antibody-positive DM in a previously healthy man in his 30s presenting with fulminant proximal muscle weakness, severe dysphagia requiring percutaneous endoscopic gastrostomy, massive anasarca (>30 kg fluid overload), respiratory failure requiring mechanical ventilation and tracheostomy, and characteristic cutaneous manifestations. MRI demonstrated diffuse myositis and elevated muscle enzymes with anti-NXP2 antibody positivity supporting the diagnosis. Treatment with pulse corticosteroids, intravenous immunoglobulin and subsequent azathioprine resulted in biochemical and clinical improvement, although the course was complicated by pulmonary embolism, pneumonia and gastrointestinal bleeding. Following prolonged immunosuppression and intensive multidisciplinary rehabilitation, the patient achieved substantial functional recovery. This case highlights the potential reversibility of even fulminant anti-NXP2-positive DM with timely aggressive treatment and rehabilitation.

Mitochondrial diseases are a prevalent cause of metabolic disorders arising from nuclear or mitochondrial DNA mutations. Their clinical and genetic heterogeneity highlight their diagnostic complexity. A 55-year-old male patient with Kallmann syndrome, retinitis pigmentosa and congenital sensorineural hearing loss presented with a one-year history of generalized weakness and imbalance. Examination revealed generalized muscle atrophy, hyporeflexia, and mild tetraparesis. Following an electromyography suggestive of proximal myopathy, muscle biopsy was consistent with mitochondrial myopathy. Mitochondrial respiratory chain analysis demonstrated increased activity of complex II and residual increases in complex I and cytochrome C. Full mitochondrial DNA sequencing identified a heteroplasmic MT-TS2 variant (m.12257G>A), with 15% heteroplasmy in blood and nearly 100% in muscle tissue. This variant was classified as likely pathogenic. This case illustrates a new potentially pathogenic variant in the MT-TS2 gene. Comprehensive analysis of mitochondrial DNA is essential to establish a definitive diagnosis.

Thyrotoxic hypokalemic paralysis is a rare complication of hyperthyroidism, characterized by acute, reversible episodes of muscle weakness associated with severe hypokalemia, secondary to intracellular potassium redistribution mediated by excess thyroid hormones and activation of the Na+/K+ - ATPase pump. Its incidence is approximately 0.2% and it occurs predominantly in males. In this report, we describe four cases of hypokalemic paralysis associated with thyrotoxicosis. All patients were male, aged between 21 and 37 years. The predominant clinical presentation was acute-onset muscle weakness, mainly proximal, with greater involvement of the lower limbs. In three of the four cases, paralysis was the main initial manifestation of hyperthyroidism due to Graves' disease. Potassium replacement combined with antithyroid therapy and beta-blockers resulted in complete resolution of the muscle weakness and adequate disease control in all patients. Therefore, thyrotoxic hypokalemic paralysis should be considered among the differential diagnoses in patients presenting with muscle weakness, as well as among the complications associated with hyperthyroidism.

Immune-mediated necrotizing myopathy (IMNM) is a variant of inflammatory myopathies, characterized by muscle fiber necrosis and regeneration with minimal inflammatory infiltration, associated with a potentially severe clinical course and difficult management. We report the case of a 64-year-old woman with a history of type 2 diabetes mellitus who presented with progressive proximal weakness, dysphagia, and prostration of one month's duration. She developed severe muscle involvement requiring subsequent mechanical ventilation. Initial studies showed markedly elevated creatine phosphokinase (CPK) levels (>10 000 U/L), and muscle biopsy revealed fiber necrosis and regeneration with scant inflammatory infiltrate, consistent with IMNM. Intensive treatment with methylprednisolone pulses and intravenous immunoglobulin was initiated, followed by the addition of methotrexate, azathioprine, and rituximab. Under this combined regimen, the patient showed a favourable evolution with progressive decline of CPK, functional recovery of muscle strength, and improvement of dysphagia, being discharged in ambulatory conditions with minimal assistance. An interdisciplinary approach and early implementation of intensive immunosuppression are essential to reverse unfavourable progression and optimize the functional prognosis of these patients.

HIV-associated myopathy is a frequent neuromuscular complication characterised mainly by inflammatory or toxic muscle involvement, leading to proximal muscle weakness. We report the case of an HIV-positive patient presenting with myopathy confirmed by electromyography. The clinical presentation was marked by symmetrical proximal muscle weakness, asthenia, anorexia, weight loss, and anaemia. A muscle biopsy was not performed. This case highlights the importance of early clinical and electrophysiological recognition for proper management.

Severe hypothyroidism left untreated can lead to the progression of a distinct hypothyroid myopathy. This unique thyroid myopathy is characterized by weakness of the proximal limb muscles with an increase in muscle mass, muscle stiffness, and cramps. There is no consistent concept or guidelines for diagnostic work-up with the typical findings of this specific myopathy. While muscle biopsy can provide additional clinical information, the majority of cases can be diagnosed clinically by the hallmark signs of muscular weakness and pseudohypertrophy of muscles in combination with elevated creatine kinase (CK) and thyroid-stimulating hormone (TSH) levels. We present a patient who developed the hallmark findings of this rare hypothyroid myopathy, in which physical exam and laboratory data provided the diagnosis. Magnetic resonance imaging or muscle biopsy could have been performed to confirm the presence of muscular pseudohypertrophy, but the cost of testing would not have altered the treatment course. Therefore, the diagnosis can be cost-effectively made without invasive diagnostic and radiologic measures.

Duchenne muscular dystrophy (DMD) is a rare X-linked recessive disorder caused by mutations in the DMD gene, resulting in the absence of functional dystrophin. The loss of dystrophin disrupts the dystrophin-associated protein complex (DAPC), leading to progressive degeneration of skeletal and cardiac muscles. Clinically, DMD is characterized by proximal muscle weakness, respiratory insufficiency, and dilated cardiomyopathy. Here, we report the generation of three induced pluripotent stem cell (iPSC) lines reprogrammed from peripheral blood mononuclear cells (PBMCs) of patients with DMD. These patient-derived iPSC lines constitute a relevant human cellular model for studying disease-associated phenotypes and evaluating potential therapeutic strategies.

Hydroxychloroquine (HCQ), chloroquine (CQ), and colchicine are widely used to treat autoimmune and inflammatory diseases but can cause toxic autophagic vacuolar myopathies. This study investigates the pathological mechanisms of HCQ/CQ- and colchicine-induced myopathies through integrated clinical, histopathological, ultrastructural, and proteomic analyses. Nine patients with clinicopathologically defined toxic myopathy (HCQ/CQ, n = 4; colchicine, n = 5) were included. Muscle biopsies were analyzed using histoenzymology, immunohistochemistry for autophagic and immune markers, electron microscopy, and proteomic profiling in selected cases. Clinically, both groups presented with proximal muscle weakness and myalgia after variable drug exposure. Histology revealed rimmed and non-rimmed vacuoles, especially in HCQ/CQ cases, and myofibrillar disorganization; the latter predominated in colchicine-treated patients. Electron microscopy confirmed myofibrillar disruption in colchicine-treated patients and autophagosomes with curvilinear bodies in HCQ/CQ cases. Immunohistochemistry showed MHC-I upregulation, heterogeneous C5b-9 deposition, and accumulation of LC3 and p62, with evidence of endoplasmic reticulum stress and transcriptional dysregulation by GRP170 overexpression and cytoplasmic MeCP2 redistribution. Proteomic analysis revealed a shared molecular signature involving immune activation, extracellular matrix remodeling, cytoskeletal stress, mitochondrial dysfunction, and dysregulation of the autophagy-lysosome pathway. Overall, HCQ/CQ- and colchicine-induced myopathies converge on common mechanisms of autophagic impairment, immune activation, and disrupted muscle homeostasis.

Primary biliary cholangitis (PBC) and immune-mediated necrotizing myositis (IMNM) are both rare autoimmune disorders, and their coexistence is uncommon. Low back pain (LBP) as the initial presentation of this overlap is extremely rare and may delay diagnosis. A case is presented of a 46-year-old woman with recurrent LBP and mild proximal muscle weakness, along with laboratory findings of elevated liver and muscle enzymes, positive anti-mitochondrial antibody subtype M2 (AMA-M2), anti-GP210, and anti-SSA antibodies, and negative myositis-specific antibodies. Imaging revealed paraspinal myositis, and histopathology confirmed PBC (stage 1) and IMNM. The patient responded well to a combination of ursodeoxycholic acid, corticosteroids, hydroxychloroquine, and mycophenolate mofetil, achieving normalization of laboratory parameters and complete symptom resolution after 15 months. This case underscores the need for clinicians to consider systemic autoimmune diseases in patients with atypical LBP and highlights the potential for AMA-M2-positive myositis to involve the paraspinal muscles, providing insight into a rare manifestation of PBC-IMNM overlap. Cite this article as: Zhu L, Yan T, Ye Q. Primary biliary cholangitis presenting with low back pain and complicated by immune-mediated necrotizing myositis: A case report. Eur J Rheumatol. 2026, 13(1), 0050, doi:10.5152/eurjrheum.2026.25050.

Abnormal synergies coexist with primary motor impairments (weakness and spasticity) after stroke. They are observed during voluntary movements and are characterized by stereotyped movement patterns, a loss of independent joint control, and abnormal muscle coordination (eg, involuntary activation of distal muscles led by proximal joint movement). The structure and expression of abnormal synergies, however, are highly context-dependent (eg, influenced by gravity, body posture, and task constraints) and are not homogeneous across patients. Current evidence suggests that abnormal synergies are pathophysiologically related to damage to corticospinal tracts, upregulation of brainstem pathways (particularly the medial reticulospinal tract, but also involves the vestibulospinal tract), and maladaptive changes in spinal circuitry. These same mechanisms may overlap with those underlying spasticity and weakness. Spasticity is believed to result from overexcitability of descending excitatory brainstem pathways, the reticulospinal tract in particular, and the consequent exaggerated stretch reflexes, while muscle weakness is attributed to the reduction in corticospinal output. Recent research and clinical observations have advanced our understanding of abnormal synergies. Post-stroke abnormal synergies are not fixed motor impairments. A new framework is proposed that suggests post-stroke abnormal synergies could constitute the behavioral expression of primary impairments, including weakness and spasticity, arising from their interactions with environmental constraints, particularly antigravity control mechanisms. The term "synergy" has been used across various frameworks, with different definitions and quantification approaches. Identifying appropriate methods to quantify abnormal synergies is therefore essential to investigate their relationship with spasticity and muscle weakness, and evaluate potential abnormal synergy improvements following interventions, even if they primarily target other motor impairments.

Dermatomyositis (DM) and hypothyroid myopathy are both treatable causes of muscle weakness and can present with overlapping clinical and laboratory features, posing a diagnostic challenge. We report the case of a young male who presented with proximal upper and lower limb muscle weakness, calf muscle hypertrophy and elevated serum creatine kinase (CK) and was found to have hypothyroidism. Muscle weakness and hyperCKemia persisted despite normalisation of thyroid function, prompting a muscle biopsy and extended autoantibody testing, which revealed anti-Ku-positive DM characterised by perivascular inflammation, perifascicular atrophy and membrane attack complex deposition. High-dose corticosteroids led to partial improvement and subsequent rituximab therapy achieved sustained clinical and biochemical remission. This case emphasises the importance of considering dual aetiology when appropriate treatment of the primary diagnosis does not yield expected results. Early biopsy and comprehensive serological evaluation could lead to excellent clinical outcomes.