Clinical Pathological Case Conference - Answer Kristin Remus, D.O. Chief Resident NYU School of Medicine, Internal Medicine August 8, 2008

Radiology Review of Radiology showed the following  Normal Chest x-ray  Lung nodule on Chest CT  Normal Abdominal CT

A diagnostic test was performed: Endoscopy and Colonoscopy with biopsies

Further Studies Stool contained Strongyloides Stercoralis larva Endoscopic studies did not show stigmata of recent bleeding Lab tests  HIV negative  Lymph node biopsy was not performed  The patient had been offered screening colonoscopy 1 year prior and declined.  Biopsies negative for H. pylori

Additional Lab Results Iron ug/dL 70 (42-146) TIBC ug/dL 189 ( ) Ferritin ng/mL (22-322) Retic % 3.77 ( ) Retic Index 2% PSA ng/mL 0.44 (0-4) CEA ng/mL <0.5 (<=5) CA-125 U/mL 14.2 (<=35) AFP ng/mL 1.5 (0-10) Serum ACE U/L 19 (9-67) Serum immunofixation – faint bands in IgG, IgM, and Kappa are present against a dense, polyclonal background. Purkinje Cell Ab - negative Hu immunoreactivity – negative Anti-ganglioside IgM <1:800 Anti-ganglioside IgG <1:100

Strongyloides Stercoralis Tropical Asia, Africa, Latin America, Southern US, Eastern Europe May persist asymptomatically in host for up to 65 years Risk factors for clinical manifestation  Chronic disease – Diabetes, Kidney Disease, Alcoholism  Immunosuppression  Hematologic malignancies  Malnutrition  HTLV-1 infection Diagnosis  Parasite found in feces, sputum, duodenal aspiration, CSF, tissue biopsy

infective larvae SOIL FECES parthenogenesis Strongyloides Life Cycle

Strongyloides Stercoralis Clinical Presentation  Skin larva currens  GI tract Cramps, diarrhea Malabsorption Rarely massive hemorrhage  Immunosuppressed Fever Lungs  larvae in sputum Many fatalities reported Cutaneous larva currens, “racing larva”

Stronglyoides Infection Immunosuppresion  Steroids may mimic endogenous parasitic-derived regulatory hormone  More eggs produced in the presence of exogenous steroids Hyperinfection  Disseminated infection Treatment  oral Ivermectin 200 ug/kg daily x 2 days, Albendazole as alternative Prevention  CDC recommends oral Ivermectin 200 ug/kg daily x 2 days for prevention in immunosuppressed  In a least one study, Thiabendazole was no more effective than placebo

Chronic Acquired Demyelinating Polyneuropathy (CADP) A group of peripheral nerve disorders  Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is a type of CADP Peak incidence 40 to 60 years, male predominance Pathophysiology unclear

CIDP Diagnostic Features Symmetric proximal and distal muscle weakness +/- sensory loss Loss of deep tendon reflexes Progressive or relapsing Time course at least 2 months Diagnosis  Cerebral spinal fluid Albuminocytologic disassocation  Nerve conduction studies  Biopsy

Concurrent Illness Variants of CIDP Several systemic disorders can occur with CIDP  HIV, Hep C  Lymphoma, Myeloma, MGUS  Inflammatory Bowel Disease  Connective Tissue Diseases  Diabetes Mellitus, Thyrotoxicosis  Nephrotic Syndrome Obligation to search for underlying cause

CIDP Clinical Course Therapy  IV Immunoglobulin (IVIg) Repeated infusions, usually 1 course/month  Corticosteroids Starting dose 100 mg Prednisone per day Tapered with clinical improvement  Plasmapheresis Progression with IV IgG or Prednisone  Immunosuppressives Mycophenolate mofetil, Cyclosporine, Methotrexate

Acquired Ichthyosis Acquired or Genetic  Acquired usually due to drugs or systemic disease Rhomboid, or fish-like, scales on the skin Symmetric, ranges in severity Primarily affects trunk, limbs, and extensor surfaces Absence of inflammatory infiltrate with hyperkeratosis is present on skin biopsy

Acquired Icthyosis Most commonly associated with Hodgkin’s Disease or and non-Hodgkin’s lymphoma  Also seen with  Transitional cell carcinoma, leiomyosarcoma, Kaposi’s Sarcoma, HCC, breast, lung, ovarian cancers  Dermatomyositis  AIDS, HTLV-1  Sarcoidosis  Thyroid disease  Malnutrition/Malabsorption  Cholesterol-lowering drugs such as Statins and Niacin No report of association with Strongyloides Obligation to look for underlying cause

Final Diagnosis Strongyloides Stercoralis invading stomach Chronic Active Gastritis Innumerable sessile colonic Polyps with tubulovillous adenoma and eosinophilic infiltrate

Acquired CIDP Proposed Pathogenesis Acquired Icthyosis ? Chronic Illness, Malnutrition High Dose Steroids Acquired Strongyloides infection GI Bleeding Gastritis Anemia ? Malabsorption Disseminated Infection ? Polyp growth Unknown disease process?

Follow Up The patient was seen in Neurology clinic 3 weeks ago. His symptoms have dramatically improved. The rash is also improving. He has had no further evidence of GI bleeding. He will likely begin Azathioprine for his CIDP once the Strongyloides infection is fully resolved.

Thank you! Dr. Martin Blaser Dr. Charles Hazzi Dr. Herman Yee Dr. Michael Macari Dr. Emma Robinson Dr. Jonathan Ralston Dr. Philip Tierno Dr. Gerald Villaneuva Dr. Malini Sahu Dr. Christina Yoon