3. Statin induced immune mediated necrotising myopathy: a case report

Abstract Introduction Statins are a commonly used group of drugs which lowers low density lipoprotein (LDL) levels by competitively inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase. Though they are effective and safe, about 0.1% patients on statins can develop severe myonecrosis or immune mediated necrotising myopathy (IMNM). Here we present a case of IMNM secondary to atorvastatin exposure, resulting in severe muscle weakness and prolonged hospitalisation, and positive treatment response to intravenous immunoglobulin (IVIG). Case description A 59-year-old Caucasian lady with a history of hypothyroidism and hyperlipidaemia, presented with 5 weeks’ history of progressive weakness in both upper and lower limbs which was preceded by flu like symptoms. She was also having swallowing difficulty and had neck-flexor weakness. There was MRC grade 2 power around hips, knees and shoulders, with normal power distally. She had been started on atorvastatin 10 mg 6 months ago, which was stopped due to myalgia. She was admitted to the hospital, and soon developed respiratory muscle weakness. She had serial SVC assessment and required nasogastric feeding. Electromyography suggested myositis. MRI of the thighs showed extensive myositis, muscle biopsy confirmed necrotising myopathy. Autoantibodies were negative, but she had high titre HMGcoA reductase antibodies (anti-HMGCR). Creatine kinase levels on presentation was 24230 U/L, which increased to 31000 U/L. Initial SVC was 33% of predicted. CT scan of chest abdomen and pelvis did not reveal any malignancy. Cardiac MRI did not reveal myocarditis, though her troponin-T levels were raised 1096 ng/L. She was non responsive to 3 pulses of 1 gm methyl-prednisolone. She was treated with IVIG, cyclophosphamide infusions and oral prednisolone. She made steady progress and was discharged with SVC of 70%, CK of 664 U/I, proximal muscle strength of 3/5 and feeding orally. She received 9 cycles of 900 mg cyclophosphamide followed by mycophenolate mofetil 2gm/day. However, her CK levels plateaued to between 650 and 700; proximal lower limb power was fluctuating between 4 and 3. She received another course of IVIG- 6 months after the onset of myositis which significantly improved her power, which sustained for around 4 months. The plan is to manage her with serial IVIG infusions. Discussion Statins can cause adverse muscle related events, ranging from mild myalgia to severe myopathy and rhabdomyolysis. Rarely, patients can develop immune mediated necrotising myositis, as in our patient. IMNM can cause persisting myositis with predominantly proximal muscle weakness, and runs a protracted course. Statin-induced IMNM is associated with presence of anti HMGCR antibodies. There are no clinical trials to guide therapeutic decisions in IMNM, however some case series and observational studies have shown improvement with immunosuppression. IVIG have been shown to be effective in anti HMGCR associated IMNM, as in our case. Even after stopping statins, IMNM can progress and patients can have prolonged weakness requiring immunosuppression. Around 50% patients continue to have significant weakness even after 2 years of treatment, indicating an unfavourable prognosis. Our patient continues to have waxing waning weakness with persistently raised CK, and IVIG infusions seems to give a rapid clinical response , though sustaining for 3 to 4 months, indicating a need for repeated infusions. The other treatment option remains rituximab, which has shown to have some efficacy in anti-SRP positive IMNM. Our patient had hypothyroidism, which is known to potentiate statin induced myopathy, however, strong association with IMNM is not established. Around 80% patients with anti HMGCR associated myositis have prior statin exposure, however, a subgroup of patients, especially among Asians, can have anti-HMGCR antibody and myositis even without statin exposure. This indicates a possible a genetic susceptibility to statins. Also, exposure to oyster mushroom and red yeast rice have been reported to be associated with anti-HMGCR antibodies in this subgroup of patients. Key learning points Statins can cause muscle related adverse events. 2-11% patients can have mild myalgia and myopathy, however necrotising myopathy is extremely rare (0.1%). Anti-HMCGCR antibodies are associated with statin induced IMNM. IMNM has a protracted course and can continue for years after stopping statins. Long term Immunosuppression is required in IMNM. IVIG is effective in refractory cases. Anti-HMCGCR antibodies can be found in statin naïve patients. Hypothyroidism can potentiate statin induced myopathy. The risk of muscle injury is higher when taking a statin which is extensively metabolised by cytochrome P450 3A4 (CYP3A4) - like simvastatin and atorvastatin, with CYP3A4 inhibitors. Pravastatin, rosuvastatin are preferred in these cases. Conflict of interest The authors declare no conflicts of interest.

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Quinine-Induced Thrombotic Microangiopathy (Q-TMA): Frequency, Presenting Features, Outcomes

Blood ◽

10.1182/blood.v128.22.1381.1381 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1381-1381 ◽

Cited By ~ 1

Author(s):

Evaren E Page ◽

Sara K. Vesely ◽

James N. George

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Conflicts Of Interest ◽

Elevated Serum ◽

Kidney Injury ◽

Long Term Outcome ◽

Presenting Symptoms ◽

Immune Mediated ◽

Organ Systems ◽

History Of

Abstract Q-TMA is an acute, severe, immune-mediated, drug-induced disorder. Q-TMA is suspected when symptoms suddenly begin within hours following quinine (Q) exposure. Diagnosis of Q-TMA is established by the history of recurrent acute symptoms following recurrent Q exposures and/or by documentation of Q-dependent antibodies reactive with platelets and/or neutrophils. The Oklahoma TTP-HUS Registry enrolls all patients for whom plasma exchange (PEX) is requested for suspected TTP or HUS. Since 1995, when routine measurement of ADAMTS13 activity began, the Registry has diagnosed 78 patients with acquired TTP (ADAMTS13 <10%). During this time we have also diagnosed 17 patients with Q-TMA; 2 additional patients were diagnosed before 1995. Seventeen of these 19 patients were tested for Q-dependent antibodies; all were positive. Nine patients had a history of recurrent acute symptoms with recurrent Q exposure, including the 2 patients not tested for Q-dependent antibodies. Q exposure was a pill in 18 patients, tonic water in one. Remarkably, 18 patients were women; all 19 patients were white. Common presenting symptoms were fever, chills, nausea and vomiting. No patients had focal neurologic abnormalities. All patients had microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and acute kidney injury. Eight patients had elevated serum alanine aminotransferase (231-1345 U/L). Three patients had neutropenia (absolute neutrophil counts, 184-486). Two patients had coagulation abnormalities suggesting disseminated coagulation (DIC). One patient died from complications of the central venous catheter insertion, performed for PEX and dialysis; all other patients recovered normal platelet counts. Three of the 18 surviving patients had end-stage renal disease (2 had kidney transplants). The median estimated glomerular filtration rate (GFR) for the other 15 patients, at 2.7-19.2 years (median, 10.2) after recovery, was 36 ml/min (range, 19-98). Only two patients had normal GFR (≥90 ml/min). Eleven patients had chronic kidney disease, defined by GFR <60 ml/min. Seven of 18 patients have died 4.1-12.7 years (median, 7.8) following recovery at ages 59-87 years. Conclusion. Quinine can cause severe immune-mediated toxicities involving multiple organ systems (Am J Hematol 2016; 91: 461). Q-TMA is an acute disorder causing severe kidney injury and, in some patients, also liver toxicity, neutropenia, and/or DIC. Q-TMA is not rare. During 20 years, we enrolled 17 Q-TMA patients compared to 78 patients with acquired TTP. Chronic kidney disease is a common long-term outcome. Explicit questions are required to discover the association of systemic symptoms with quinine ingestion. Table Table. Disclosures No relevant conflicts of interest to declare.

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8. Myositis as an idiosyncratic drug reaction to leflunomide

Rheumatology Advances in Practice ◽

10.1093/rap/rkz030.007 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Cited By ~ 1

Author(s):

Angeline Darren ◽

Kirsty Levasseur ◽

Priyanka Chandratre

Keyword(s):

Rheumatoid Arthritis ◽

Muscle Weakness ◽

Conflicts Of Interest ◽

Oral Contraceptive Pill ◽

Lower Limbs ◽

Drug Induced ◽

Lateral Muscle ◽

Wide Range ◽

Patient Reported ◽

Autoimmune Condition

Abstract Introduction Myositis is a broad diagnosis with a number of potential causes. There are numerous drugs that can lead to myotoxicity. We discuss a case of a patient with known rheumatoid arthritis who developed myositis with no evidence of an additional autoimmune condition and where the most likely cause seems to be leflunomide. Case description A 46-year-old Asian lady with a background of seropositive rheumatoid arthritis and overactive bladder developed increasing muscle weakness. Disease activity was well-controlled on leflunomide which had been started four years ago after an initial trial of methotrexate proved ineffective. Other regular medications include tolterodine and rigevidon (combined oral contraceptive pill), paracetamol and co-codamol. She presented to her GP in February with generalised muscle weakness, fatigue, dry mouth, hair loss and occasional shortness of breath on exertion. Blood tests showed elevated CK at 1132 u/l, ALT 57 u/l (AST normal), LDH 302 u/L, CRP 4 mg/l and ESR 25mm/h. Further tests were subsequently arranged following rheumatology review including ANA and ENA (both negative), an extended myositis panel and HMGCoAR antibodies (also negative). MRI of her lower limbs showed bilateral oedema within the anterior and lateral muscle compartments of her thighs, worse on the left, and in keeping with myositis. Given the possibility of leflunomide being the cause of her symptoms it was stopped. Her CK one month after stopping leflunomide had decreased to 819 u/l and then 389 u/l after four months. The patient reported improvement in her muscle weakness, CK is currently being monitored, and she is awaiting an EMG. A muscle biopsy has been discussed with her previously and although she had refused initially, in view of persistent mild elevation in CK, the biopsy and leflunomide washout will be discussed again with her again. As she is clinically asymptomatic and not keen to try new medications, further immunosuppression has not been started. Discussion Myositis is seen in a wide range of conditions with numerous possible causes. It can be drug-induced, secondary to viral infections or caused by autoimmune conditions including overlap conditions and idiopathic inflammatory myopathies. Drug-induced myositis is most commonly associated with statins, but has been seen with many different medications. Leflunomide is a disease-modifying anti rheumatic drug used particularly in the treatment of inflammatory arthritis but has also been used in treatment resistant dermatomyositis. It inhibits the mitochondrial enzyme, dihydroorotate dehydrogenase to reduce the reproduction of rapidly dividing cells. A rise in CK is considered a common side effect. We have only found one other case report where leflunomide was suspected to have induced polymyositis, also in a patient with rheumatoid arthritis. Both biochemical and clinical improvement following cessation of leflunomide, with no other inventions raises the likelihood of this being a leflunomide-induced myositis. Key learning points When faced with a patient with rheumatoid arthritis presenting with symptoms suggestive of myositis, whilst an overlap autoimmune condition is a possibility, it is important to consider potential drug causes. Numerous drugs have been implicated through both direct myotoxicity and immunologically mediated myotoxicity. Importantly for rheumatologists these can include glucocorticoids, antimalarial drugs, colchicine and tumour necrosis factor inhibitors. According to the summary of product characteristics a rise in CK is commonly seen with leflunomide but clinical myositis has only been reported rarely. Conflicts of interest The authors have declared no conflicts of interest.

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Metabolic and Inflamatory Proteins Differently Expressed in Platelets From Deep Venous Thrombosis Patients

Blood ◽

10.1182/blood.v118.21.5256.5256 ◽

2011 ◽

Vol 118 (21) ◽

pp. 5256-5256

Author(s):

Mariane Cristina Flores Nascimento ◽

Karina Kleinfelder-Fontanesi ◽

Fernanda Loureiro de Andrade Orsi ◽

Steven H Seeholzer ◽

Harry Ischiropoulos ◽

...

Keyword(s):

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Conflicts Of Interest ◽

Lower Limbs ◽

Apolipoprotein A1 ◽

Blood Samples ◽

Orbitrap Mass Spectrometer ◽

Inflammatory Processes ◽

History Of

Abstract Abstract 5256 BACKGROUND: Deep venous thrombosis (DVT) is multi-causal disease associated to a high morbi-mortality due to complications as pulmonary embolism and post-flebitic syndrome. The incidence is about 20 to 30%, and 25% of the patients will present recurrence in 5 years. The identification of new risk factors is important in clinical practice to prevent new thrombotic events. The role of the platelets on DVT is still not well defined. AIM: The objective of this study was to analyze the hole proteins profile of platelets obtained from DVT patients and compare to the same matherial derived from healthy controls. PATIENTS: peripheral blood samples were collected from 3 spontaneous DVT patients and from 1 sibling and 1 neighbor for each patient in order to minimize the genetic and environmental interferences. These patients presented spontaneous and recurrent episodes of lower limbs proximal DVT and all of them mentioned a familiar history of coagulation disorders. METHODS: the platelets were washed, lysed, and the proteins were alkylated, reduced, precipitated with acetone and hydrolyzed by trypsin. 100mg of peptides were then separated by hydrophobicity using HPLC, and 8 fractions were obtained and directed to the LTQ-Orbitrap mass spectrometer. The proteins search was performed by Sorcerer-SEQUEST. RESULTS: We identified 5 proteins that were present on patients and absent in all the controls: Apolipoprotein A1 Binding-Protein, Coatomer (z1 sub-unit), Estradiol 11–17-b Dehydrogenase, Leucotriene A-4 Hydrolase and Sorbitol Dehydrogenase. Western-Blotting was performed with specific antibodies and validated the results. CONCLUSIONS: with this study it was possible to identify proteins up to date non-related to the physiopathology of DVT, that could be involved with metabolic and inflammatory processes. Disclosures: No relevant conflicts of interest to declare.

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Severe Proximal Myopathy with Remarkable Recovery after Vitamin D Treatment

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100007083 ◽

2009 ◽

Vol 36 (03) ◽

pp. 336-339 ◽

Cited By ~ 41

Author(s):

Yousef A. Al-Said ◽

Hiyam S. Al-Rached ◽

Hussien A. Al-Qahtani ◽

Mohammed M.S. Jan

Keyword(s):

Vitamin D ◽

Saudi Arabia ◽

Vitamin D Deficiency ◽

Muscle Weakness ◽

Bound States ◽

Calcium Supplementation ◽

Lower Limbs ◽

Proximal Muscle Weakness ◽

Proximal Muscle ◽

Remarkable Recovery

Background:Osteomalacia is an uncommon cause of muscle weakness. Our objectives were to describe features of myopathy associated with Vitamin D deficiency and examine the contributing factors leading to osteomalacic myopathy in our region.Methods:Patients identified retrospectively for the six year period ending in December 2006 with the diagnosis of osteomalacia and/or Vitamin D deficiency associated proximal muscle weakness were included. They were followed in three major centers in western Saudi Arabia. Clinical, biochemical, radiological, and electrophysiological findings were collected before and after Vitamin D treatment by chart review.Results:Forty seven female patients aged 13-46 years (mean 23.5, SD 4.5) were included. All were veiled and covered heavily when outside the house for social and cultural reasons. Only eight (17%) had adequate varied diet with daily milk ingestion. All patients presented with progressive proximal muscle weakness lasting 6-24 months (mean 14) prior to our evaluation. The weakness was severe in six (13%) patients leading to wheel chair bound states. Associated musculoskeletal pain involving the back, hips, or lower limbs was common (66%). Osteomalcia was the referral diagnosis in only 11 patients and the remaining 36 (77%) patients were misdiagnosed. All patients had metabolic and radiological profiles suggestive of osteomalacia. Remarkable recovery was documented in all patients following oral cholecalciferol and calcium supplementation.Conclusions:Vitamin D deficiency is an important treatable cause of osteomalacic myopathy in Saudi Arabia. The diagnosis is frequently delayed or missed. Screening for Vitamin D deficiency in patients with acquired myopathy is needed to identify this treatable disorder.

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1. TIF1-γ associated dermatomyositis

Rheumatology Advances in Practice ◽

10.1093/rap/rkz030 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Rosemary Waller ◽

Nadia Ahmad

Keyword(s):

Conflicts Of Interest ◽

Case Reports ◽

Strong Association ◽

Lung Nodule ◽

Lower Limbs ◽

Mediastinal Lymphadenopathy ◽

Uneventful Recovery ◽

High Dose ◽

Shortness Of Breath ◽

History Of

Abstract Introduction This is a case of a patient presenting at the age of 39 with dermatomyositis. Subsequent investigations revealed her to have a TIFI-γ antibody and a metastatic colon adenocarcinoma. She was initially steroid responsive and her malignancy simultaneously responded to chemotherapy. A relapse of her malignancy was preceded by a flare in her dermatomyositis which proved to be non-responsive to steroids and further chemotherapy. Case description The patient presented to rheumatology at the age of 39 with a few-week history of a photosensitive rash on her face, upper chest and hands. This was followed by rapidly progressive symmetrical proximal and truncal muscle weakness and pain. She described dysphagia to solids and shortness of breath on exertion. She had a very short history of weight loss, attributed to reduced oral intake. She had no relevant past medical history and was taking no medications. Examination revealed power of 3/5 in both upper and lower limbs, a heliotrope rash with Gottrons papules with normal cardiovascular and respiratory examinations. CK at presentation was 3709. Haematology and biochemistry was otherwise normal. MRI thighs showed extensive myositis. ANA was positive with a positive TIFI-γ antibody. CT scan showed a proximal sigmoid mass with local and mediastinal lymphadenopathy and a 6mm lung nodule. Histology from a mediastinal node confirmed a metastatic adenocarcinoma. Initially, the patient was treated as an autoimmue dermatomyositis with pulsed IV methylprednisolone followed by high dose prednisolone. She responded rapidly both clinically and biochemically to steroids. Following the diagnosis of malignancy, she underwent a hemicolectomy from which she made an uneventful recovery. She then completed 12 cycles of oxaliplatin and 5FU chemotherapy, with interval CT scanning showing good partial response to treatment and she returned to work. One month after completing chemotherapy, whilst still taking prednisolone her rash reoccurred. This rapidly progressed despite an increase in her steroids and quickly became associated with weakness and further shortness of breath. CT showed a progression of her malignancy with carcinomatosis lymphangiitis. She received one cycle of Irinotecan before being admitted with neutropenic sepsis and progression of her cancer. At this time she decided to withdraw all treatment and died shortly afterwards at the age of 40, 18 months after her initial presentation. Discussion TIF1-γ antibodies were first identified in 2006 and are involved in cell regeneration, apoptosis and innate immunity. High levels of TIFI-Y are found in the nuclei of regenerating myofibres. They are associated with dermatomyositis and are found in between 13 – 31% of adults and 22 – 29% of children. There is a strong association with malignancy in those aged over 39 (positive predictive value of 58%, sensitivity 78%, specificity 89%). There are no case reports of malignancy associated with TIF1- Y antibodies in patients under the age of 39. Malignancy typically presents early in the course of dermatomyositis, being diagnosed at presentation or within 8 months. There are case reports of TIF1- Y antibodies co-existing with Mi2 antibodies, increasing malignancy risk. In younger patients this association with cancer is not seen but the antibody is associated with skin ulceration and chronic disease. It is hypothesised that differences in HLA regions and protein conformation may account for these different phenotypes. Patients typically have a lower CK and there is a higher incidence of amyopathic dermatomyositis compared with other myositis specific antibodies. Our patient was at the lower end of the risk spectrum for malignancy and had no localising symptoms for this. She was initially very steroid responsive, which again lowered our threshold for suspicion of malignancy. Indeed, her CT was requested on the basis of shortness of breath looking for interstitial lung disease rather than anything more sinister. Key learning points TIF1-γ antibodies have a strong association with malignancy in patients over the age of 39. Clinicians should have a high index of suspicion even in the absence of symptoms of malignancy. Malignancy associated dermatomyositis can be steroid responsive. A relapse of dermatomyositis should raise suspicion for a relapse of malignancy. Conflicts of interest The authors have declared no conflicts of interest.

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Guillain-Barre Syndrome following COVID-19 Infection: First Case Report from Kuwait and Review of the Literature

Dubai Medical Journal ◽

10.1159/000513382 ◽

2021 ◽

pp. 1-5

Author(s):

Walaa A. Kamel ◽

Ismail Ibrahim Ismail ◽

Jasem Yousef Al-Hashel

Keyword(s):

Intravenous Immunoglobulins ◽

Lower Limbs ◽

Guillain Barre Syndrome ◽

Global Pandemic ◽

First Case ◽

Immune Mediated ◽

Guillain Barré Syndrome ◽

Electrophysiological Studies ◽

History Of ◽

Guillain Barré

Objective: Guillain-Barré syndrome (GBS) is an acute immune-mediated polyradiculoneuropathy that is often related to a previous infectious exposure. GBS emerged as a potentially serious complication of coronavirus disease 2019 (COVID-19) since its declaration as a global pandemic. We report the first case from Kuwait, to the best of our knowledge. Clinical Presentation: A 72-year-old male presented with 3 weeks history of acute progressive and ascending lower limbs weakness. He developed these symptoms 3 weeks after testing positive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Electrophysiological studies showed acute demyelinating polyradiculoneuropathy and cerebrospinal fluid showed protein-cell dissociation. He was successfully treated with intravenous immunoglobulins (IVIGs). Conclusion: Neurologists should be aware of GBS as a potentially serious complication associated with COVID-19. Our patient had a favorable outcome with IVIG with no autonomic or respiratory affection.

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Immune-Mediated Hematologic Complications of Checkpoint Inhibitors: A Review of the Literature

Blood ◽

10.1182/blood-2018-99-113341 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5883-5883 ◽

Cited By ~ 1

Author(s):

Omar Sallam ◽

Irbaz Bin Riaz ◽

Ronald S. Go

Keyword(s):

Clinical Trials ◽

Hemolytic Anemia ◽

Autoimmune Hemolytic Anemia ◽

Immune Thrombocytopenia ◽

Conflicts Of Interest ◽

Checkpoint Inhibitors ◽

Case Reports ◽

Case Series ◽

Immune Mediated ◽

Immune Neutropenia

Abstract Background: The incidence and types of hematologic complications from immune check point inhibitors are not well known. We conducted this review to describe immune-mediated hematologic complications reported in clinical trials, case series, and case reports. Methods: A pre-defined comprehensive search strategy was used to identify case reports, case series, and clinical trials using PubMed. Any study that reported hematologic complications was included. Data were extracted for demographic characteristics and occurrence of immune-mediated hematologic complications. We pooled the data to calculate the frequency of immune-mediated hematologic adverse effects. Results: A total of 689 of studies were retrieved using the search criteria and 75 were included in the analysis (31 case reports and case series and 44 clinical trials). There were 44 patients reported having immune-mediated hematologic complications, 4 of them in clinical trials. The complications included aplastic anemia, autoimmune hemolytic anemia, cryoglobulinemia, graft versus host disease, hemophilia A (acquired), immune neutropenia, immune thrombocytopenia, macrophage activation syndrome, myelodysplastic syndrome, pure red cell aplasia, and thrombotic thrombocytopenic purpura. However, the overall rates were very low, ranging from 1-2.2% in clinical trials. Immune thrombocytopenia was the most common (29.5%), followed by autoimmune hemolytic anemia (15.9%), and immune neutropenia (13.6%). Immune-mediated hematologic complications were reported in all classes of checkpoint inhibitors including anti-programmed cell death protein 1 (nivolumab and pembrolizumab), anti-programmed death ligand 1 (avelumab and durvalumab), and anti-cytotoxic T-lymphocyte-associated protein 4 inhibitors (ipilimumab and tremelimumab). Among patients reported in case reports and case series, the median age was 57 years (range, 29-85) and most were males (52.9%). The majority of the complications occurred in patients treated with ipilimumab (38.8%), nivolumab (27.7%) and pembrolizumab (16.0%). The onset was usually within the first week of receiving the first dose but could occur up to 17 months after drug initiation. Indefinite discontinuation of the immunotherapy was the mainstay of treatment resulting in resolution of complications in the majority (74.5%) of the patients. Two patients were re-challenged with the same checkpoint inhibitor and one experienced a relapse of immune cytopenia (autoimmune hemolytic anemia). Conclusion: Immune-mediated hematologic complications associated with checkpoint inhibitors are rare. They are usually reversible after discontinuation of such treatment. Relapses may occur with re-challenge. Disclosures No relevant conflicts of interest to declare.

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Isolated Oropharyngeal Dysphagia as the Initial Presentation of Anti-SRP Immune-Mediated Necrotizing Myopathy

Journal of Health Science and Medical Research ◽

10.31584/jhsmr.2020760 ◽

2020 ◽

Author(s):

Pat Korathanakhun ◽

Thanyalak Amornpojnimman

Keyword(s):

Muscle Weakness ◽

Clinical Course ◽

Signal Recognition Particle ◽

Oropharyngeal Dysphagia ◽

Signal Recognition ◽

Proximal Muscle Weakness ◽

Proximal Muscle ◽

Necrotizing Myopathy ◽

Immune Mediated ◽

Electrodiagnostic Study

A 51-year-old male initially presented with a progressive course of isolated oropharyngeal dysphagia prior to the clinical course of painful symmetrical proximal muscle weakness without sensory deficit which rendered him to wheelchairbound status within 5 months. The physical examination revealed symmetrical proximal muscle weakness without sensory symptoms. The initial serum creatine kinase was extremely high and the electrodiagnostic study revealed a myopathic pattern. A muscle biopsy of the left biceps suggested a diagnosis of immune-mediated necrotizing myopathy (IMNM) and the serum anti-signal recognition particle (SRP) autoantibody was finally detected. This case presented a rare form of anti-SRP IMNM in which isolated oropharyngeal dysphagia preceded the onset of proximal muscle weakness.

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Rapidly Progressive Proximal Weakness

10.1093/med/9780197583425.003.0049 ◽

2021 ◽

pp. 152-153

Author(s):

Teerin Liewluck ◽

Margherita Milone

Keyword(s):

Creatine Kinase ◽

Mycophenolate Mofetil ◽

Intravenous Immunoglobulin ◽

Muscle Weakness ◽

Creatine Kinase Level ◽

Coenzyme A ◽

Immune Mediated ◽

Necrotizing Autoimmune Myopathy ◽

History Of ◽

Autoimmune Myopathy

A 53-year-old woman had development of subacute-onset muscle weakness resulting in difficulty climbing stairs, rising from a chair, and reaching over her shoulders. She reported no dysphagia, dysarthria, dyspnea, or diplopia. She also disclosed no rash, joint pain, or urine discoloration. She had no history of statin exposure. There was no family history of neuromuscular disorders, early cataracts, cardiac arrhythmia, or cardiomyopathy. Two months of treatment with prednisone had resulted in no clinical improvement. Neurologic examination indicated moderate neck flexor, shoulder, and hip girdle muscle weakness, with sparing of cranial muscles. There was no action- or percussion-induced myotonia. Needle electromyography showed short-duration, low-amplitude, and complex motor unit potentials, predominantly affecting proximal muscles, associated with fibrillation potentials and myotonic discharges in proximal and axial muscles. Her creatine kinase level was increased. Biopsy of the left quadriceps showed variation in muscle fiber size, a moderate increase in internalized nuclei, fiber splitting, and scattered necrotic and regenerating fibers. There was a mild increase in perimysial fibrous and fatty connective tissue. 3-Hydroxy-3-methylglutaryl–coenzyme A reductase antibodies were strongly positive. The patient was diagnosed with hydroxy-3-methylglutaryl–coenzyme A reductase antibody–positive necrotizing autoimmune myopathy. The patient received intravenous immunoglobulin and mycophenolate mofetil while continuing prednisone. At 1-year follow-up, she had no weakness, and her creatine kinase value was normal while she continued taking prednisone, mycophenolate mofetil, and intravenous immunoglobulin. Necrotizing autoimmune myopathy, or immune-mediated necrotizing myopathy, is a subtype of immune-mediated myopathy, clinically characterized by subacute, progressive, proximal limb weakness and persistently increased creatine kinase level. Pathologically, it is characterized by myonecrosis with minimal or no inflammation. One-third of patients with necrotizing autoimmune myopathy have myalgia.

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10. Warning: statin-induced autoimmune necrotising myositis

Rheumatology Advances in Practice ◽

10.1093/rap/rkz030.009 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Cited By ~ 1

Author(s):

Muhamad Jasim ◽

Jafar Ibrahim ◽

William Scotton ◽

Francesco Manfredonia ◽

Margaret Timmons ◽

...

Keyword(s):

Type 2 Diabetes ◽

Muscle Weakness ◽

Muscle Biopsy ◽

Conflicts Of Interest ◽

Steroid Treatment ◽

Good Effect ◽

Close Monitoring ◽

Proximal Muscle Weakness ◽

Proximal Muscle

Abstract Introduction Statins are frequently prescribed, following or in order to prevent cardiovascular events. They inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoA), an enzyme involved in cholesterol synthesis. Up to 20% of patients experience myalgia which resolve after the drug is stopped. We highlight a more serious and potentially life-threatening complication: statin-induced autoimmune necrotising myositis (SIANM). Recently SIANM has been differentiated from inflammatory polymyositis. Patients present with bilateral proximal muscle weakness, elevated creatinine kinase, a muscle biopsy with necrosis and a positive HMGCoA reductase antibody. The latter has been found to be a specific and sensitive investigation for SIANM. Case description Given the rarity of SIANM, no guidelines available recommend a best course of treatment, here we highlight 3 successfully treated patients. Case 1: 72-year-old man with hypercholesterolaemia, type 2 diabetes and hypertension presented with progressive proximal symmetrical weakness for 6 months. He started 20mg atorvastatin a year earlier and stopped this 2 months before admission. Examination revealed 4/5 muscle strength proximally in all 4 limbs and the patient struggled to stand from sitting. CK was elevated at 8223 IU/L (30-200). EMG confirmed a myopathic process and MRI thighs showed active inflammation. A muscle biopsy and HMGCoA antibodies confirmed SIANM and the patient commenced IV and then oral steroids. The patient deteriorated rapidly over the subsequent days with progressive weakness and dysphonia. He developed bilateral pneumonias and was admitted to ITU. Here we commenced the patient on IV immunoglobulin (IVIG) and rituximab. With this he improved significantly, with increasing power and a normalised CK. Case 2: 55-year-old old man with a background of previous MI in 2013 (after which he commenced atorvastatin), type 2 diabetes, hypercholesterolemia and hypertension presented with progressive bilateral proximal muscle weakness. Serum CK found to be 8413, his statin was stopped and the patient underwent extensive investigation. Once again investigations confirmed the diagnosis of SIANM. The patient commenced steroid treatment but despite initial improvement in his power, this soon plateaued as did his CK. He was commenced on IVIG and methotrexate and found significant benefit with these treatments. Case 3: 60-year-old lady presented with a 5-month history of generalised aches and pains with difficulty standing from sitting. She had been on atorvastatin for many years but her symptoms did not improve despite having stopped this 5 months previously. Investigations confirmed a SIANM. The patient was commenced on steroids and methotrexate with good effect. Discussion Patients presenting on statins with proximal symmetrical weakness and a raised CK should have HMGCOA antibodies checked as part of a myositis screen. Though statins should always be stopped, patients with SIANM can continue to deteriorate despite drug discontinuation and steroid treatment. Such patients should be considered for immunosuppression. The 3 cases described show positive response to a combination of methotrexate, IVIG and/or rituximab. This seems to mirror the growing clinical experience in other published case reports. Key learning points Patients presenting on statins with proximal symmetrical weakness and a raised CK should have HMGCOA antibodies checked as part of a myositis screen. Withdrawal of the statin and steroid treatment alone is often insufficient to successfully treat SIANM. Close monitoring of a patient’s power and CK levels are required even after withdrawal of a statin and treatment with steroid as patients can continue to deteriorate. In such cases, additional treatment with methotrexate, IVIG and/ or rituximab appears to have the best outcomes. Conflicts of interest The authors have declared no conflicts of interest.

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