Tag Archives: Rheumatology

Inclusion Body Myositis 101

General information

  • Most common muscle disease in patients older than 50 years. More common in white men, but can affect any group
  • Thought to be degenerative, rather than auto-immune. Associated with systemic autoimmune or connective-tissue diseases in up to 15 %

Clinical Manifestations

  • Difficulty with everyday tasks predominantly requiring the use of proximal muscles, such as getting up from a chair, climbing steps, stepping onto a curb, lifting objects, or combing their hair
  • Fine-motor movements that depend on the strength of distal muscles (especially foot extensors and finger flexors), such as buttoning a shirt, sewing, knitting, or writing, are affected fairly early in the course
  • The pharyngeal and neck-flexor muscles are often involved, causing dysphagia or fatigue and difficulty in holding up the head
  • May also progress slowly for years, and its clinical features may simulate those of limb-girdle muscular dystrophy.
  • Consider IBM in patients with polymyositis or dermatomyositis that is resistant to treatment.

Diagnostic Criteria

  • Muscle strength – myopathic muscle weakness with early involvement of the distal muscles
  • EMG – myopathic with mixed potentials
  • Muscle enzymes – normal or elevated
  • Muscle biopsy – definitive
  • Light microscopy —  endomysial inflammation, rimmed vacoules distributed around the edge, eosinophilic cytoplasmic inclusions
  • EM — granules contain membranous whorls. Filamentous inclusions in the cytoplasm or nucleus, prominent in the vicinity of the rimmed vacuoles, are pathognomonic

Treatment

  • Inclusion-body myositis is generally resistant to all therapies, and its rate of progression also appears to be unaffected by treatment.
  • Failed therapies — Steroids, MTX, Cyclophosphamide, Beta-interferon, TNF-a inhibitors, ATGAM, IVIg
  • Future possibilities
    • Alemtuzumab, a T-cell–depleting monoclonal antibody; reported slowed disease progression, improvement of strength in some patients, and reduction in endomysial inflammation
    • Follistatin, an antagonist of the myostatin pathway, has been shown to produce a dramatic increase in muscle mass in animals
    • Arimoclomol, a heat shock protein (HSP) coinducer may slow down the process of protein misfolding and aggregation

Grand Rounds Review: Chronic Back Pain

This morning, Dr. Una Makris, from the UT Southwestern Division of Rheumatology, gave an excellent talk on the diagnosis and management of chronic low back pain in older adults, a problem that costs more annually than most chronic medical conditions. In her talk, she noted that a multi-modal approach, with physical therapy, cognitive behavioral therapy, pain control, and a host of other methods to deal with this problem. Significant research in the area suggests that we are over-treating and over-spending, without a considerable impact on the burden of this often debilitating condition. In fact, a recent article in the JAMA notes that among older adults with a new primary care visit for back pain, early imaging was not associated with better 1-year outcomes. For more information, check out the articles below:

Internal Medicine Journal Watch – April 2015

STRAIGHT FROM THE HOUSESTAFF – the April 2015 UT Southwestern Internal Medicine Journal Watch! They have summarized important issues in clinical practice, from alcoholic hepatitis to which medications to use for stroke prevention in afib. Make sure to take the EKG challenge at the end! You will have to view this post on our website to access the PDF.  There is a quick run down of the topics below:

Hepatology

  • Corticosteroids in severe alcoholic hepatitis after recent upper GI bleed. Dr. Jan Petrasek reviewing Rudler et al., J Hepatol. 2015 Apr;62(4):816-21. 10.1016/j.jhep.2014.11.003. Epub 2014 Nov 11.
  • Serum ammonia level for the evaluation of hepatic encephalopathy. Dr. Jan Petrasek reviewing Ge et al., JAMA. 2014 Aug 13;312(6):643-4.

Rheumatology

  • Extended report: Prediction of cardiovascular risk in rheumatoid arthritis: performance of original and adapted SCORE algorithms. Dr. Brian Skaug reviewing Arts, et al. Ann Rheum Dis. 2015 Feb 17. pii: annrheumdis-2014-206879. doi: 10.1136/annrheumdis-2014-206879

Pulmonary/Critical Care

  • Trial of Early, Goal-Directed Resuscitation for Septic Shock [The Protocolised Management in Sepsis (ProMISe) Trial]. Dr. James Galloway reviewing Mouncey PR et al. N Engl J Med. 2015;372(14):1301-11.
  • A Randomized Trial of Icatibant in ACE-Inhibitor-Induced Angioedema. Dr. James Galloway reviewing Bas M, et al. N Engl J Med. 2015;372(5):418-25.

Nephrology

  • High-Sensitivity Troponin T and N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) and Risk of Incident Heart Failure in Patients with CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study. Dr. Natalia Rocha reviewing Bansal N, et al. JASN 2015; 26:946-956
  • Preoperative renin–angiotensin system inhibitors use linked to reduced acute kidney injury: a systematic review and meta-analysis. Dr. Natalia Rocha reviewing Cheungpasitporn W, et al. Nephrol. Dial. Transplant. 2015; doi: 10.1093/ndt/gfv023

Cardiology

  • Which drug should we use for stroke prevention in atrial fibrillation? Dr. Douglas Darden reviewing Lau, Yee C.; Lip, Gregory Y.H. Current Opinion in Cardiology. 2014 July 29 (4): 293-300.
  • EKG CHALLENGE: Contributed by Dr. Jeanney Lew

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All of the work above comes from the IMJW Editorial Board: Jan Petrasek, Brian Skaug, Ben Galloway, Natalia Rocha, Doug Darden, and Jeanney Lew!

“What’s that syndrome with erythema nodosum and sarcoidosis?”

Lofgren syndrome! Below is a quick 101 cheat sheet on Lofgren syndrome, check it out!

  • Lofgren syndrome is a form of acute sarcoidosis (not to be confused with Loffler’s syndrome)
  • Initially described in 1953 by Sven Halvar Lofgren, a Swedish clinician
  • More common in Scandinavian, Irish and African populations
  • The syndrome is comprised of the combination of
  • Erythema Nodosum
  • Hilar adenopathy
  • Migratory polyarthralgia
  • Fever
  • In men, more common to have bilateral ankle arthritis instead of EN
  • The combination of all features of Lofgren syndrome has a 95% specificity for sarcoidosis, allowing for clinical diagnosis without pathology
  • However, consider the ddx for EN and hilar adenopathy: primary TB, sarcoid, coccidiodomycosis, histo, blasto, yersiniosis and chlamydia
  • The syndrome is associated with a good prognosis
  • Some patients have spontaneous remission and others require only NSAIDs to control their symptoms
  • In one retrospective study of 80 patients, 67% were treated with NSAIDs and 41% with steroids and only 17% had a recurrence

Neuro-Behcet Disease

General Information

  • Excluding headaches, neurological complications of Behçet syndrome (neuro-Behçet syndrome) occur in less than 12% of cases, often a few years after the onset of the other systemic features.

Clinical Manifestations and Diagnosis

  • In parenchymal disease, meningoencephalitis occurs, with a mixed inflammatory cell infiltrate leading to necrosis and apoptotic neuronal loss. Inflammatory infiltration, rather than fibrinoid necrosis, is seen around small vessels.
    • The brainstem and mid-brain are the most commonly affected areas, but spinal cord lesions and cerebral involvement may also occur and, occasionally, neuro-Behçet syndrome presents as a pseudotumour cerebri.
    • Brainstem involvement usually presents subacutely, with headache, cranial neuropathies or cerebellar or corticospinal tract dysfunction.
    • Sensorineural hearing loss can occur, resulting in sudden deafness, balance disturbances and dizziness.
    • The characteristic MRI lesion in parenchymal neuro-Behçet syndrome is a unilateral upper brainstem lesion extending into the thalamus and basal ganglia.
    • Analysis of cerebrospinal fluid shows a neutrophilic (in early disease) or lymphocytic (in late disease) pleocytosis, but usually no oligoclonal bands.
  • Neurovascular disease accounts for approximately 20% of cases of neuro-Behçet syndrome and symptoms include dural sinus thrombosis, intracranial aneurysm and extracranial aneurysm and/or dissection.
    • The clinical findings are usually limited to those of intracranial hypertension (that is, headache, vomiting, altered levels of consciousness and papilloedema).
    • Intracranial hypertension may be present without MRI abnormalities and should be managed in the same way as idiopathic benign intracranial hypertension.
    • Aneurysms of the cerebral, vertebral and carotid arteries can also occur.

Management

  • Headaches are often under-treated. An effort should be made to classify the type of headache and, in the case of migraine, agents such as pizotifen and β­blockers should be offered.
  • Parenchymal disease:
    • Initial Management: treated with high-dose steroids in the first instance, along with initiation of a DMARD, usually azathioprine.
      • Methotrexate, mycophenolate, cyclophosphamide, tacrolimus and IFN-­α are probably effective, although evidence is lacking.
      • Cyclosporin is potentially neurotoxic and should not be used for patients with a history of CNS disease.
    • The alternative therapeutic option for severe and aggressive disease is the early use of a biologic agent (i.e. anti-TNF therapy, like infliximab)
  • Neurovascular disease:
    • Cerebral vascular thrombosis and aneurysms also require aggressive immunosuppression.
    • Anti-coagulation for venous thrombosis needs to be assessed on a case-by-case basis.

Ambrose, N. L. & Haskard, D. O. Nat. Rev. Rheumatol. 9, 79–89 (2013); published online 25 September 2012; doi:10.1038/nrrheum.2012.156

The Anti-Nuclear Antibody (ANA!)

Patterns of ANA and Disease Associations

Homogenous pattern

  • Anti dsDNA
    • Specificity for SLE 95% – false positive in some hepatitis
    • Sensitivity 40-60% in SLE
    • One of 11 criteria for SLE
    • Predicts flares: may predate nephritis
  • Anti-Histone
    • Drug-induced lupus (procainamide, hydralazine, aldomet, dilantin, INH, tegretol)
    • Best for negative predictive value

Speckled pattern (ENA or acid extractable nuclear antigens)

  • Anti-Smith
    • 99% specific, 20% sensitive for SLE
  • Anti U1-RNP
    • 30-40% sensitive for SLE (associated with Raynaud’s and less severe clinical course)
    • Mixed connective tissue disease:
      • Nearly 100% sensitive
      • SLE, Raynaud’s, myositis, non-erosive arthritis, puffy hands, esophageal dysmotility, sicca, scleroderma-like
      • Other CTD: 2-5% scleroderma, 24% PM/scleroderma overlap, 4-17% PM/DM
    • Anti Ro (SSA) and La (SSB)
      • In primary Sjogren’s: Anti-SSA 88-96% and Anti SSB 71-87%
        • Associated with increased severity (vasculitis, hypergammaglobulinemia, lympho/leukopenia)
      • SLE: SSA 25%, SSB 10%
      • Neonatal lupus: 90%

Nucleolar (RNA-associated antigens)

  • Anti SCL-70 (Topoisomerase I)
    • 95% of patients with scleroderma – predicts more subacute, progressive, systemic disease
    • Diffuse scleroderma: 25-75% sensitivity, 93% specificity
    • CREST 13%
  • Anti PM-SCL: polymyositis/scleroderma overlap syndromes

Centromere

  • Limited scleroderma: 60-80%
  • Isolated Raynaud’s: 25% – may predict risk of CREST
  • Primary biliary cirrhosis
  • Normal: nearly 1% of female blood donors

Peripheral

  • Antibodies to nuclear envelope, seen with staining for dsDNA in older systems

Cytoplasmic

  • Mitochondrial pattern: primary biliary cirrosis, autoimmune hepatitis, IBD, scleroderma
  • Anti Jo-1 (speckled cytoplasmic)
    • 20-40% of patients with dermatomyositis, polymyositis, mixed PM/DM
    • Higher prevalence of ILD (20-25%)

 

Clinical Pearls – Hidden Clue on Skin Exam

Pathergy phenomenon is when a small red bump or pustule occurs 1 to 2 days after a forearm is pricked with a sterile needle. This test is often associated with Behcet’s disease having a low sensitivity but high specificity for the disease, as a positive test supports a diagnosis of Behcet’s and is not definite. This past week’s NEJM had a case of a patient with newly diagnosed Behcet’s disease and a positive pathergy test. Click on the links below to read the article from NEJM and learn more from the Hopkins Vasculitis Center.

pathergytest1

(image courtesy of The Johns Hopkins Vasculitis Center)

The Johns Hopkins Vasculitis Center – Behcet’s Disease

A 25-Year Old Man with Oral Ulcers, Rash, and Odynophagia 

Internal Medicine Journal Watch – February 2015

STRAIGHT FROM THE HOUSESTAFF – the February 2015 Internal Medicine Journal Watch! They have summarized important issues in clinical practice, from Metformin in CKD to pre-exposure prophylaxis for HIV. There is even an EKG challenge at the end, if you are up for it! You will have to view this post on our website to access the PDF.  There is a quick run down of the topics below:

Endocrinology

  • American Diabetes Association’s Standards of Medical Care in Diabetes – 2015.
    • Dr. Jeremy Warshauer reviewing Grant RW, et al. Diabetes Care 2015 Jan;38 Supplement 1
  • Metformin in Patients With Type 2 Diabetes and Kidney Disease: A Systematic Review
    • Dr. Nicolas Barros reviewing Inzucchi, SE, et al. JAMA 2014; 312(24):2668-2675

Rheumatology

  • Preliminary analysis of the Very Early Diagnosis of Systemic Sclerosis (VEDOSS) EUSTAR multicentre study: evidence for puffy fingers as a pivotal sign for suspicion of systemic sclerosis
    • Dr. Brian Skaug reviewing Minier T, et al. Ann Rheum Dis 2014;73: 2087–2093

Healthcare Policy

  • Using drugs to discriminate – adverse selection in the insurance marketplace
    • Dr. Ashish Gupta reviewing Jacobs DB and Sommers BD. N Engl J Med. 2015 Jan 29;372(5):399-402

General Internal Medicine

  • Disorders of Plasma Sodium — Causes, Consequences, and Correction
    • Dr. Nicolas Barros reviewing Sterns, R, et al. NEJM 2015; 372:55-65
  • Acid–Base Problems in Diabetic Ketoacidosis
    • Dr. Nicolas Barros reviewing Kamel K, et al. NEJM 2015 ; 372:546-554

Platelet Transfusion

  • A Clinical Practice Guideline From the AABB
    • Dr. Nicolas Barros reviewing Kaufman RN, et al. Ann Intern Med. 2015 Feb 3;162(3):205-13

Nephrology

  • Association of Albumin-Creatinine Ratio and Cystatin C With Change in Ankle-Brachial Index: The Multi-Ethnic Study of Atherosclerosis (MESA)
    • Dr. Ben Jenny reviewing Garimella P, et al. Am J Kidney Dis. 2015;65(1):33-40

Infectious Disease

  • Tenofovir-Based Preexposure Prophylaxis for HIV Infection Among African Women
    • Dr. Brad Cutrell and Dr. Nicolas Barros reviewing Marrazzo J, et al. 2015; 372:509-518
  • Infectious Diseases Diagnosis and Treatment of C. difficile in Adults: Systematic Review
    • Dr. Brad Cutrell and Dr. Nicolas Barros reviewing Bagdasarian N, et al. JAMA 2015; 313(4):398-408

Hepatology

  • An interferon-free antiviral regimen for HCV after liver transplantation
    • Dr. Jan Petrasek reviewing Kwo et al., NEJM. 2014; Dec 18;371(25):2375-82
  • Decreasing Mortality Among Patients Hospitalized with Cirrhosis in the United States From 2002 through 2010
    • Dr. Jan Petrasek reviewing Schmidt et al., Gastroenterology. 2015 Jan 23.

Cardiology

  • Twelve or 30 Months of Dual Antiplatelet Therapy after Drug-Eluting Stents (DAPT trial)
    • Dr. Ben Jenny reviewing Mauri L, et al. N Engl J Med. 2014 Dec 4;371(23):2155-66.

EKG Challenge

  • Dr. Ben Jenny
  • Untitled
All of the work above comes from the IMJW Editorial Board (with Dr. Brad Cuttrell): Jan Petrasek, Purav Mody, Nicolas Barros, Ragisha Gopalakrishnan, Jeremy Warshauer, Shetal Patel,  Ben Jenny (not Jennings), Vishwanatha Lanka, Brian Skaug, Ashish Gupta, and Roma Mehta!