Nemaline myopathy in newly diagnosed systemic lupus erythematosus and Sjögren's overlap syndrome complicated by macrophage activation syndrome.

BACKGROUND: Nemaline myopathies are congenital or acquired muscle disorders that typically present in childhood but can occasionally occur in adults with underlying malignant, infectious or autoimmune disorders. There is a great genetic heterogeneity as well as clinical variability among the disease. CASE PRESENTATION: Here, we present a case of nemaline myopathy in a young woman who was newly diagnosed with systemic lupus erythematosus (SLE) and Sjögren's overlap syndrome complicated by macrophage activation syndrome (MAS). She had no personal or family history of myopathy and was reporting progressive thigh weakness. A muscle biopsy revealed type 1 myofiber predominance with granular material in atrophic myocytes consistent with nemaline myopathy. Her symptoms markedly improved with immunotherapy for her SLE and MAS supporting the diagnosis of sporadic late-onset nemaline myopathy (SLONM) associated with her autoimmune disease. CONCLUSIONS: 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 appears to improve symptoms of myopathy.

Statin-Associated Necrotizing Autoimmune Myositis Complicated by an Uncommon Adverse Effect to Treatment.

Statin-associated necrotizing autoimmune myositis (NAM) is an autoimmune condition characterized by severe acute-onset proximal muscle weakness, a very high creatinine kinase (CK) level, and prominent myofiber necrosis and minimal lymphocytic infiltration on muscle biopsy. Unlike self-limited statin myopathy, this condition usually requires aggressive immunomodulation therapy to assist recovery and prevent future disability. In this case report, we present a patient who developed progressive muscle weakness after taking atorvastatin for one year. At initial presentation, her CK level was 28,000 U/L. She was diagnosed with statin-associated NAM and started on high-dose intravenous solumedrol, mycophenolate, and intravenous immunoglobulin (IVIG) therapy. However, she subsequently developed acute bilateral vision loss and right side hemineglect; she was diagnosed with posterior reversible encephalopathy syndrome (PRES), thought to be a possible delayed adverse reaction to IVIG. IVIG was discontinued, and the patient was treated with supportive therapy. At six-month follow-up, she had significant improvement in muscle strength and vision.

An Interesting Case of Neurobrucellosis Mimicking Neuropsychiatric Lupus.

This case describes a patient presenting with acute onset papilledema, subacute strokes resulting in upper extremity weakness and numbness, arthritis, maculopapular rash, depressed C4 and CH50, and a high titer anti-double-stranded DNA antibody. The patient was given the diagnosis of probable systemic lupus erythematosus, which was supported by the Systemic Lupus International Collaborating Clinics (SLICC) criteria. He was aggressively treated for neuropsychiatric lupus (NPSLE) with pulse dose steroids and a dose of intravenous cyclophosphamide. Blood cultures drawn on admission later grew out 2/4 bottles of Gram-variable bacteria, speciated as Brucella melitensis by PCR. Serum Brucella serologies were also positive. On further evaluation, the patient noted a history of eating unpasteurized cheese in Mexico. Given these additional findings, the patient's presentation was most consistent with a diagnosis of neurobrucellosis. Steroids were tapered off, no further doses of cyclophosphamide were given, and a prolonged course of intravenous and oral antibiotic therapy was administered, resulting in complete resolution of the patient's presenting symptoms.

A Rare Case of Digital Ischemia and Gangrene in ANCA-Associated Vasculitis with Review of the Literature.

This paper describes one patient with Antineutrophil Cytoplasmic Antibody- (ANCA-) associated vasculitis who initially presented with multiple ischemic fingers and toes. On further evaluation, the patient was also found to have pulmonary-renal involvement and episcleritis. The diagnosis was supported with a positive cANCA (anti-proteinase 3) and a bronchoscopy consistent with diffuse alveolar hemorrhage. Although the patient refused a tissue biopsy, clinical presentation including nasal ulceration, sinus congestion, and epistaxis and anti-proteinase 3 antibody were more consistent with Granulomatosis with Polyangiitis (GPA) rather than Microscopic Polyangiitis (MPA) or Eosinophilic Granulomatosis with Polyangiitis (EGPA) based on the recently presented ACR/EULAR Provisional 2017 Classification Criteria for GPA (Luqmani et al., 2016). The patient responded well to therapy including high dose steroids and cyclophosphamide, with improvement of all organs involved and had no further digital ischemia or gangrene on follow-up. We include a review of the English literature summarizing presentation, management, and outcome of 16 similar cases.

Fever, Myositis, and Paralysis: Is This Inflammatory Myopathy or Neuroinvasive Disease?

West Nile virus (WNV) is a mosquito-borne RNA Flavivirus which emerged in North America in 1999. Most patients present with a febrile illness but a few develop WNV neuroinvasive disease. Myopathy is an uncommon manifestation. We describe a case of a 42-year-old male from Los Angeles who presented with 8 days of fever and muscle pain. Initial physical exam was normal except for 4/5 muscle strength testing in his extremity proximal muscles. Laboratory revealed a creatine kinase of 45,000 and a urinalysis with large blood but no red blood cells, suggesting rhabdomyolysis. The patient's condition declined despite aggressive supportive care and hydration, and on hospital day #6 he developed severe altered mental status and progressed to complete right arm paralysis and 2/5 muscle strength in bilateral legs. EMG/NCS showed sensorimotor axonal polyneuropathy and the cerebrospinal fluid was positive for IgM and IgG WNV antibodies. The patient was diagnosed with WNV neuroinvasive disease, poliomyelitis (and encephalitis) type with myopathy/muscle involvement. He was treated supportively and his muscle and neurologic disease gradually improved. At 12-month follow-up his muscle enzymes had normalized and his weakness had improved to 5/5 strength in bilateral legs and 3/5 strength in the right arm.

Acute hemorrhagic myositis in inflammatory myopathy and review of the literature.

We describe two patients with dermatomyositis that presented with interstitial lung disease, positive V and Shawl sign who developed acute spontaneous abdominal/retroperitoneal bleed. Both patients expired despite aggressive treatment and resuscitation. Hemorrhagic myositis in these two patients with inflammatory myopathy is a very rare complication. The association of anti-Ro52 with this potentially very serious complication remains unclear. This potential relationship should be further evaluated in future studies.

Intranuclear protein transduction through a nucleoside salvage pathway.

Regulation of gene expression by intranuclear transduction of macromolecules such as transcription factors is an alternative to gene therapy for the treatment of numerous diseases. The identification of an effective intranuclear delivery vehicle and pathway for the transport of therapeutic macromolecules across plasma and nuclear membranes, however, has posed a significant challenge. The anti-DNA antibody fragment 3E10 Fv has received attention as a novel molecular delivery vehicle due to its penetration into living cells with specific nuclear localization, absence of toxicity, and successful delivery of therapeutic cargo proteins in vitro and in vivo. Elucidation of the pathway that allows 3E10 Fv to cross cell membranes is critical to the development of new molecular therapies. Here we show that 3E10 Fv penetrates cells through a nucleoside salvage transporter. 3E10 Fv is unable to penetrate into cells deficient in the equilibrative nucleoside transporter ENT2, and reconstitution of ENT2 into ENT2-deficient cells restores 3E10 Fv transport into cell nuclei. Our results represent the first demonstration of protein transport through a nucleoside salvage pathway. We expect that our finding will facilitate a variety of methods of gene regulation in the treatment of human diseases, open up new avenues of research in nucleoside salvage pathways, and enhance our understanding of the pathophysiology of autoimmune diseases.