Narendranath Epperla

Blessing for the Bleeder: Bevacizumab in Hereditary Hemorrhagic Telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) is a genetic disorder characterized by uncontrolled multisystem angiogenesis with epistaxis, gastrointestinal bleeding, iron-deficiency anemia, and arteriovenous malformations, and is often associated with increased levels of vascular endothelial growth factor (VEGF). Bevacizumab, a VEGF inhibitor, reduces epistaxis, telangiectasias, and iron-deficiency anemia. We present the case of a woman with HHT and chronic gastrointestinal bleeding who required iron supplementation and multiple blood transfusions. Bevacizumab resulted in marked symptom improvement and transfusion-independence. Our report describes the dose schedule and calls for a randomized, controlled trial demonstrating the value of bevacizumab therapy.

Sjogren's syndrome and neuromyelitis optica spectrum disorders (NMOSD)--a case report and review of literature.

BackgroundNeuromyelitis optica (NMO) is a rare relapsing auto-immune disease of the central nervous system which is sometimes found in association with other autoimmune disorders including Sjogren’s syndrome. We present the case of a middle aged female with Sjogren’s syndrome (SS) and Neuromyelitis optica spectrum disorders (NMOSD) who had a rapidly declining neurological illness that responded to immunosuppressive therapy.Case presentationA 51-year-old female with Sjogren’s syndrome and recent history of varicella zoster infection presented with right upper and lower extremity weakness of one week duration. She was noted to have contrast enhancement at C2-C4 cord levels on cervico-thoracic MRI. Comprehensive work up was negative except for presence of a mild lymphocytic pleocytosis and oligoclonal bands in the CSF. She was diagnosed with transverse myelitis secondary to varicella zoster infection and was treated with high dose steroids in addition to acyclovir with improvement in her symptoms. Two months later she developed left upper and lower extremity weakness, bilateral dysesthesias and urinary incontinence. Repeat MRI of the cervico-thoracic spine revealed worsening enhancement at lower cervical cord levels (C5-7) with extension to T1. CSF analysis was unchanged; however immunological work up was abnormal for elevated NMO-IgG/AQP4 antibody. She was diagnosed with NMOSD and was treated with immunosuppressive therapy. Initially with IV methylprednisone and Cyclophosphamide therapy followed by Mycophenolate mofetil (MMF) maintenance therapy with good response. Repeat MRI 6 months later showed near complete resolution of previous abnormal cord signal changes.ConclusionOne needs to recognize the relationship between autoimmune diseases especially SS and NMOSD. The presence of NMO antibody has been associated with a relapsing disease course and a careful follow-up, besides use of remission maintenance agents such as MMF and Azathioprine are important to consider.

Genetic evidence of PTPN22 effects on chronic lymphocytic leukemia

To the editor: The recent article by Negro et al represents a thorough investigation into the effect of Lyp, the gene product of PTPN22 , on BCR signaling in the pathogenesis and progression of chronic lymphocytic leukemia (CLL).[1][1] This study shows that increased Lyp enhances Akt, a serine/

Topical timolol for treatment of epistaxis in hereditary haemorrhagic telangiectasia associated with bradycardia: a look at CYP2D6 metabolising variants

A 59-year-old man presented to the emergency department with lightheadedness. He had started intranasal administration of ophthalmic timolol for the prevention of epistaxis associated with hereditary haemorrhagic telangiectasia approximately 3 weeks earlier with excellent response. His heart rate was about half its normal rate, an ECG revealed sinus bradycardia, and it was determined he had significant cardiac issues in his family history. Essentially all other tests were normal. The discontinuation of the intranasal use of timolol resolved any further episodes of lightheadedness and bradycardia. It was determined through genetic testing that he is an intermediate metaboliser of CYP2D6, the main enzyme contributing to the metabolism of timolol. This explains the development of the bradycardia after intranasal timolol use. The metabolising variants of CYP2D6 need to be considered when prescribing medications metabolised by this enzyme, so possible adverse effects can be avoided.

ADAMTS13 Deficiency and Thrombotic Thrombocytopenic Purpura Associated with Trimethoprim-Sulfamethoxazole

Thrombotic thrombocytopenic purpura (TTP) is a hematological disease characterized by microangiopathic hemolytic anemia and thrombocytopenia. Although the link between ADAMTS13 deficiency and idiopathic TTP has been well-established, the role of trimethoprim-sulfamethoxazole (TMP-SMX) in the pathogenesis of TTP is not yet well elucidated. To the best of our knowledge, there have been only two previous reports linking this medication with the development of TTP. We present the case of a healthy woman, age 26 years, who developed TTP during TMP-SMX therapy for urinary tract infection. She was found to have ADAMTS13 deficiency with anti-ADAMTS13 antibodies. Her condition responded to discontinuation of the TMP-SMX, plasmapheresis, and rituximab therapy. We speculate that the acquired ADAMTS13 deficiency might have been triggered by the TMP-SMX therapy.

Sweet’s Syndrome: One Disease, Multiple Faces

Corresponding author: Received: April 7, 2011 Yusuf Kasirye, MD Revised: June 8, 2011 Department of Internal Medicine Accepted: June 15, 2011 Marshfield Clinic 1000 North Oak Ave doi: 10.3121/cmr.2011.1012 Marshfield, WI 54449 USA Tel: 715-387-5537 Fax: 715-389-5757 Email: kasirye.yusuf@marshfieldclinic.org . Published online ahead of print August 4, 2011 as doi:10.3121/cmr.2011.1012 Rapid Release CM&R

Radiographic findings in Waldenström's macroglobulinemia resembling fibrogenesis imperfecta ossium (FIO): A case report

A case of Waldenström’s macroglobulinemia with radiographic features of fibrogenesis imperfecta ossium is presented. The case raises the possibility that these radiographic findings might be more common in Waldenström’s macroglobulinemia than previously appreciated, and illustrates the need for bone biopsy to establish a definitive diagnosis of fibrogenesis imperfecta ossium.

Brain Abscesses Complicating Acute Pneumococcal Meningitis During Etanercept Therapy

Brain abscess formation as a sequelae of community-acquired pneumococcal meningitis is extremely rare, accounting for less than 1% of all meningitis complications. Although metastatic seeding from a distal peripheral septic focus has been observed, this phenomenon most commonly occurs in the context of ear, nose and throat infections, post-cranial neurosurgical procedures, traumatic open cranial injury, or immunosuppression. We present the case of a man, 61 years old, on etanercept therapy for ankylosing spondylitis who developed multiple brain abscesses as a complication of pneumococcal meningitis. We believe that the predisposition to this extremely rare complication of a particularly aggressive pneumococcal meningitis was most likely due to the underlying immunosuppression resulting from etanercept therapy. As far as we know, this case is the first report linking multiple brain abscess formation in a patient with community-acquired pneumococcal meningitis with etanercept therapy.

An uncommon cause of acquired osteosclerosis in adults: hepatitis C-associated osteosclerosis

Hepatitis C-associated osteosclerosis (HCAO) is a rare sclerosing bone condition characterized by debilitating, predominantly lower extremity bone pain, accelerated bone turnover, and a generalized increase in histologically normal trabecular and cortical bone tissue. Herein we report the clinical presentation and imaging results of the 19th case of HCAO. Clinicians, particularly those caring for a population at risk for HCV infection, should be aware of this uncommon condition. The etio-pathogenesis of HCAO remains obscure but may bear important lessons in bone biology that could lead to new treatment options for osteoporosis.

Appearances are Deceptive: Staphylococcus Superinfection of Clavicular Tuberculous Osteomyelitis

A man, aged 25 years, presented with pain, swelling, and drainage from the right clavicular area. He had a past history of abscess at the sternoclavicular joint. The cultures from the drainage site grew methicillin-sensitive Staphylococcus aureus, and he was placed on appropriate antibiotics. As S. aureus infection of the clavicle is often secondary in nature, particularly in adults, a thorough workup was done to identify the underlying cause. Quantiferon gold, done as a part of the workup, came back positive, while the bone cultures grew S. aureus and Mycobacterium tuberculosis. He was placed on 9 months of combination therapy for tuberculosis osteomyelitis with a good clinical outcome.