Nemaline myopathies are among the most frequent congenital myopathies. They are hallmarked by rod- or thread-shaped cytoplasmic bodies and named after nema, the Greek word for thread . Nemaline bodies are derived from degenerated Z-bands and stain positive on immunohistochemistry for Z-band proteins, such as alpha-actinin and myotilin . They are visualized as fine cytoplasmic aggregates on light microscopy and can be confirmed by high electron density similar to Z-bands on electron microscopy . Given their association with plasma cell dyscrasias, HIV and autoimmune disorders, immune dysregulation likely plays a key role in their etiology [6, 7]. Another possible explanation for their appearance includes an unrecognized viral infection as a possible trigger [6, 7].
There is a great genetic heterogeneity as well as clinical variability among the disease. The majority of congenital nemaline myopathies present in infancy or childhood, although some have been reported to be relatively asymptomatic until early adulthood. Sporadic late-onset nemaline myopathies (SLONM) on the other hand typically present in adults after the age of 40 and are commonly associated with MGUS and multiple myeloma and can less frequently be associated with HIV [1, 2], although an association with autoimmune disorders has also been described [5,6,7]. They are sometimes referred to as “myopathies with rods” to distinguish them from congenital nemaline myopathies .
Congenital nemaline myopathies are characterized by hypotonia and a predominantly proximal muscle weakness involving the face, neck flexors and proximal extremities . Respiratory symptoms are frequently noted and range from asymptomatic restriction seen on pulmonary function testing to sudden respiratory failure in infancy . Treatment is generally supportive.
Sporadic late-onset nemaline myopathy (SLONM) typically presents with weakness of the proximal upper and lower extremities, dyspnea, dysarthria and dysphagia . SLONM associated with MGUS tends to have a more severe course with rapid progression to respiratory failure compared with SLONM associated with HIV . Muscle pathology typically shows fiber type disproportion and type 1 fiber predominance, as seen in our patient . Treatments that have been suggested for SLONM with MGUS are IVIG as well as anti-plasma cell dyscrasia therapy including autologous stem-cell transplantation following high-dose melphalan [1, 3]. HIV-associated nemaline myopathy on the other hand has been reported to respond to immunosuppressive therapy . It is unclear whether SLONM and HIV-NM represent two separate disease entities.
To our knowledge, there have only been two other case reports published describing adult-onset nemaline myopathy in patients with SLE. One of the patients had symptoms of muscle weakness since infancy which was found to be secondary to congenital nemaline myopathy . The other case was thought to be secondary to SLONM and improved with rituximab and cyclophosphamide . Another case report delineates a case of SLONM in a patient with primary Sjögren’s syndrome with symptoms responding to steroids and IVIG .
The case of SLE associated with SLONM was described in a 41-year-old woman who was diagnosed with SLE six years prior. She was suffering from significant muscle weakness since her diagnosis of SLE, which progressed until she was unable to walk without bilateral support. CK level and serum electrophoresis were normal; HIV testing was negative. A deltoid muscle biopsy revealed myofibers with nemaline rods, which were confirmed on electron microscopy. Her weakness eventually responded to rituximab and cyclophosphamide which were started for her concurrent lupus nephritis .
The case of Sjögren’s syndrome and SLONM was reported in a 58-year-old woman who presented with progressive muscle weakness that progressed over the course of two years causing severe difficulty walking. She had a normal serum CK and negative HIV testing. A modified Gomori trichrome stain of a quadriceps muscle biopsy showed rods in more than half of the muscle fibers, many of them irregular and punctuate, which were confirmed on EM. Fiber type proportions were noted to be normal. The patient’s symptoms improved with steroids and IVIG .
Our patient presented with subjective weakness confined to her bilateral proximal lower limbs. Her personal and family histories were negative for any kind of myopathies and with absence of known consanguinity. An MRI of the pelvis showed abnormal muscle signal on fluid-sensitive sequences indicating edema of the muscles of the pelvis and proximal thighs that appeared most severe in the gluteus muscles. A quadriceps biopsy revealed type 1 myofiber predominance with granular material in atrophic myocytes consistent with nemaline myopathy. Her symptoms markedly improved after initiation of immunotherapy for SLE and MAS with hydroxychloroquine, dexamethasone, cyclosporine and mycophenolate mofetil. All of these features make a diagnosis of SLONM associated with SLE and Sjögren’s syndrome highly likely.
Limitations of our case report include the lack of workup for MGUS/multiple myeloma including serum/urine electrophoresis and immunofixation.
In conclusion, SLONM is a type of nemaline myopathy that presents in adults and can occasionally be associated with autoimmune disease. In these cases, treatment of the underlying disorder with immunosuppression can improve symptoms of myopathy.