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SYNDROMES MASQUERADING AS INFECTIONS
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Syndromes that masquerade as infections
• We will tackle questions and cases
• Fever is often a presenting symptom
• Or can present in a way that is similar to an infectious syndrome like pneumonia, cellulitis, wound infection, or septic arthritis
• There are many; we will cover a few today
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Question • A 25 yo M is referred to you for recurrent fevers lasting 2-3 days.
• Fevers are sometimes accompanied by arthralgias of the ankles
or other joints• Recurrent bouts of testicular and abdominal pain that last 24 to
48 hours. Surgery for hydrocele did not improve the pain. • No pleuritis, genital ulcers, rash history of STI. Occasional oral
ulcers• Exam normal vital signs, no rashes, several oral aphthous
ulcerations, plantar tenderness and mildly swollen knees• Labs CRP of 3.0 mg/dl (normal 0–0.8) and neg RF. UA
showed trace proteinuria. Ferritin 300 (normal 40-200)
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Question• The most likely diagnosis is• A. Familial Mediterranean Fever• B. Adult Still’s Disease• C. Kikuchi’s Disease• D. Behcet’s disease
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Question • The most likely diagnosis is• A. Familial Mediterranean Fever• B. Adult Still’s Disease• C. Kikuchi’s Disease• D. Behcet’s disease
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Familial Mediterranean Fever• Autosomal recessive• Occurs primarily in Jews, Armenians, Turks, Arabs in the
Mediterranean basin, central Asia, and Japan• Can occur at any age, but 80% of cases occur before age
of 20• M:F 1.5-2• Episodic attacks
• last from 24-72 hours• Moderate to high fever• Painful serositis including abdominal pain
• Mutation in MEFV gene leading to alteration in pyrin protein
• Treatment: colchicine
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Recurrent Ulcers
• 40 yo Caribbean woman referred for refractory oral ulcers.
• No response to valacyclovir
• Low grade fevers at home, poor appetite, weight loss
• Then developed ulcers pictured at right
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© THE STANFORD PROGRAM ON INTERNATIONAL AND CROSS-CULTURAL EDUCATION
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Fever
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Question• A 68 yo man presented with several months of fevers
followed by precordial chest pain for 1 week. He also reported generalized fatigue, weight loss, and night sweats.
• PE: T 101.7°F. His physical examination results were unremarkable. No murmur or rub was noted on cardiac examination.
• Labs: WBC 8.3 K/mm3, Plt 301 K/mm3. ESR 99, CRP 161.9. Cr: 2.1. u/a: 3+ protein
• EKG showed pericarditis. Transthoracic and transesophageal echocardiograms showed a moderate pericardial effusion, but no vegetations
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Question• The most likely diagnosis is:• A. Myocardial infarction• B. Coxsackievirus infection• C. Purulent pericarditis with S. aures• D. Systemic lupus erythematosus
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Question• The most likely diagnosis is:• A. Myocardial infarction• B. Coxsackievirus infection• C. Purulent pericarditis with S. aureus• D. Systemic lupus erythematosus
Antinuclear antibody titer was 1:340 (n = <1:40) and an anti–double-stranded DNA titer was 1:640
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SLE – Dx Criteria• Malar rash• Discoid rash• Photosensitivity• Oral ulcers• Arthritis (non-erosive)• Serositis• Renal disorder• Neurologic disorder (sz,
psychosis)• Hematologic disorder• Immunologic disorder
• Anti-DNA, anti-Sm, APLA
• ANA+
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Copyright © 2012 American Medical Association. All rights reserved.
From: A Comprehensive Evidence-Based Approach to Fever of Unknown OriginArch Intern Med. 2003;163(5):545-551. doi:10.1001/archinte.163.5.545
The percentage of patients with fever of unknown origin by cause over the past 40 years.
Figure Legend:
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• What is the workup for FUO?
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Obligatory tests: ESR or CRP, CBC with diff, CMP, SPEP, LDH, CK, ANA, RF, blood cultures (x3), urine Cx, chest X-ray, abdominal ultrasonography (or CT), PPD or IGRA
2nd Level: BM biopsy, temporal artery biopsy in patients older than 55 years, funduscopy, abdominal CT, and chest CT.
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Question
• 64 yo man has had repeated bouts of tenderness of the cartilaginous part of both ears that typically last for one to two weeks.
• No SOB, chest pain, dyspnea, or any eye complaints during these episodes. He had symptoms of degenerative arthritis but did not have evidence of joint effusions
Am Fam Physician. 2002 Jul 1;66(1):141-142.
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Question
• Which one of the following is the most likely diagnosis?
• A. Cellulitis of the ear.• B. Allergic contact dermatitis.• C. Chronic cutaneous (discoid) lupus.
• D. Superficial basal cell carcinoma.
• E. Relapsing polychondritis.
Am Fam Physician. 2002 Jul 1;66(1):141-142.
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Question
• Which one of the following is the most likely diagnosis?
• A. Cellulitis of the ear.• B. Allergic contact dermatitis.• C. Chronic cutaneous (discoid) lupus.
• D. Superficial basal cell carcinoma.
• E. Relapsing polychondritis.
Am Fam Physician. 2002 Jul 1;66(1):141-142.
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www.uptodate.com www.nejm.org
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Relapsing Polychondritis• Systemic inflammatory process that affects cartilage• Can involve
• Ears (auricular chondritis)• Joints (nonerosive, seronegative inflammatory polyarthritis)• Nose (nasal chondritis)• Eyes (conjunctivitis, keratitis, scleritis/episcleritis, uveitis)• Respiratory tract chondritis (laryngeal and/or tracheal cartilages)• Ears/vestibular system (neurosensory hearing loss, tinnitus, and/or
vertigo)• Heart (valvular disease)
• Clinical diagnostic criteria• Occurs in all races and groups, male = female• Treated with glucocorticoids, other immunosuppressants
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Saddle Nose Deformity• Syphilis• Lepromatous leprosy• Relapsing polychondritis• Granulomatosis with polyangiitis (Wegner’s
granlulomatosis)• Cocaine abuse
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Question• A 54 yo man with a history of laryngeal cancer was
admitted to the hospital for evaluation of fever and of a painful, erythematous eruption on back and chest. The patient denied any recent trauma, travel, gardening, or exposure to animals. No recent chemotherapy or radiation treatments.
• PE T 101.4, well demarcated, ecchymotic, tender, plaques were noted on back and chest, neck.
• Labs WBC 13k (86% PMN), Plt 404, Cr 1.3. • The patient was given broad-spectrum antibiotics, but his
condition did not improve.
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Néstor P. Sánchez. Atlas of Dermatology in Internal Medicine
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Question• The most likely diagnosis is:• A. Sweet’s syndrome• B. Drug eruption• C. Dermatomyositis• D. HSV
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Question• The most likely diagnosis is:• A. Sweet’s syndrome• B. Drug eruption• C. Dermatomyositis• D. HSV
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Sweet’s Syndrome• Acute febrile neutrophilic dermatosis• Characterized by
• Painful erythematous or eccymotic plaques, papules or nodules• Fever • Leukocytosis• Typical histologic features
• Can be associated with infection (URI or GI infection - Yersinia), malignancy (esp heme malignancies), drugs (including GCSF)
• Lesions are more commonly on face, neck, UE • Path – edema, dense neutrophilic infiltrate in dermis• Treatment: glucocorticoids
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Néstor P. Sánchez. Atlas of Dermatology in Internal Medicine
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Dermatomyositis
http://dermatlas.med.jhmi.eduAm Fam Physician. 2002 Oct 1;66(7):1285-1286.
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Question • These skin lesions are associated with:
• A. Amyloidosis• B. Ulcerative colitis• C. Vibrio species infection• D. Cryptococcal infection
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Question
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Question • These skin lesions are associated with:
• A. Amyloidosis• B. Ulcerative colitis• C. Vibrio species infection• D. Crytococcal infection
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Question • These skin lesions are associated with:
• A. Amyloidosis• B. Ulcerative colitis• C. Vibrio species infection• D. Crytococcal infection
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Pyoderma Gangrenosum• Characterized by irregular, boggy, blue-red ulcers with
undermined borders and purulent necrotic base• Acutely, painful pustule or nodule that ulcerates• Can be associated with systemic diseases, esp UC• Histology: neutrophilic inflammation with abscess
formation and necrosis (not specific for PG)• Slight trauma (biopsy, blood draw) can initiate new PG
lesions• Treatment: immunosuppression or immune modulation
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http://dermatlas.med.jhmi.edu
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More PG at a Surgical Site
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Question • A 45 yo W is evaluated for a 2-month history of
fatigue, nonproductive cough, decreased appetite, intermittent fever, RUQ pain, and a 4.5-kg (10.0-lb) weight loss.
• PE T 37.8°C (100.0°F), BP 104/68, HR 100/min, and RR 16, BMI 28. Several erythematous 5- to 10-mm maculopapular lesions on face. Cardiopulm normal, Hepatomegaly. B/L inguinal LAD
• Labs: • hgbn 12.2 g/dL; phos 4.0 mg/dL; ca 11.2 mg/dL, Cr, 2.0 mg/dL• urinalysis, 1+ protein; 20 leukocytes/hpf • PPD negative. Urine cx negative
• Chest radiograph shows bilateral hilar lymphadenopathy. Renal u/s: rt kidney is 13.7 cm and lt kidney is 15.4 cm. No hydro, no stones
Ann Intern Med. 01 May 2012;156(9):ITC5-1http://dermatlas.med.jhmi.edu
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Question • Which of the following is the most likely diagnosis?• A. Amyloidosis• B. Sarcoidosis• C. The Sjögren syndrome• D. Systemic lupus erythematosus
Ann Intern Med. 01 May 2012;156(9):ITC5-1
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Question• Which of the following is the most likely diagnosis?• A. Amyloidosis• B. Sarcoidosis• C. The Sjögren syndrome• D. Systemic lupus erythematosus
Ann Intern Med. 01 May 2012;156(9):ITC5-1
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Sarcoidosis• Idiopathic granulomatous disease• Can affect any organ• In the US, more common in African Americans• Common presenting signs and symptoms: cough, fever
and weight loss, chest pain, painful ankle swelling, painful nodules on shins, eye pain
• Variable clinical course• Clinical features, imaging, histopathology contribute to the
diagnosis• Treatment: prednisone
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Question• A 21 yo man is evaluated for a 5-day history of pain and
swelling in the right ankle. 7 days ago, he developed a nodule on the left leg. He has no history of trauma to either of these sites.
• PE: VS are normal. The right ankle is warm and swollen, and range of motion elicits pain. He also has a warm, firm, 2-cm erythematous nodule over the anterior left lower extremity that is tender to palpation and has been present for 7 days.
• A plain x-ray of the right ankle is normal. • Arthrocentesis of the right ankle is performed, and synovial
fluid analysis reveals a leukocyte count of 3000/μL (80% lymphocytes,12% macrophages). No crystals.
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Question• Which of the following is the most likely diagnosis?
• A. Bacterial arthritis• B. Crystal-induced arthritis• C. Osteoarthritis• D. Sarcoidosis
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Question• Which of the following is the most likely
diagnosis?• A. Bacterial arthritis• B. Crystal-induced arthritis• C. Osteoarthritis• D. Sarcoidosis
• Lofgren syndrome: acute monoarticular arthritis (ankles typically), erythema nodusum, and hilar LAD.
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Organ Involvement in Sarcoidosis*
Figure Legend:Ann Intern Med. 01 May 2012;156(9):ITC5-1
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Granulomatous Inflammation
• Distinct pattern of chronic inflammatory reaction in which the predominant cell type is an activated macrophage with a modified epithelial-like appearance
• A granuloma is a focal area of granulomatous inflammation consisting of an aggregation of macrophages that are transformed into epithelial-like cells surrounded by a collar of mononuclear leukocytes
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Sarraf Vol. 7; Issue 8; 13 May 2005
wikipedia
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Question• 29 yo woman originally from Puerto Rico with HIV (on
ARVs, CD4 209) admitted with fever, nausea and vomiting.
• Fever on and off for 2 years, +night sweats, 45 pound weight loss
• PE T 102, tender left sided cervial LAD, bl supraclavicular LAD, lungs clear
• Labs WBC 5.7, HCT 32, Cr 0.7, LFTs WNL• Biopsy of cervical LN showed granulomas on frozen
section.
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What would you do next?
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• Team started empiric TB treatment • Final path: lymph nodes with necrotizing granulomas • GMS stain showed small budding yeast • Culture positive for fungi at 10 days that ultimately grew
Histoplasma capsulatum.
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Granulomatous Inflammation• Infection
• Fungi• Histo, cocci, blasto, sporothrix,
aspergillus, crypto• Parasites
• Toxo, Leish, schistosomiasis• Spirochetes
• T. pallidum• Mycobacteria
• M. tuberbulosis, M. leprae, M. kansasii, M. marinum, M. avian
• Bacteria• Brucella, Yersinia, Bartonella,
Nocardia, Actinomyces• Misc
• Whipple’s disease, Kikuchi (?)
• Vasculitis• Granulomatosis with
polyangiitis, Churg-Strauss, GCA, SLE, polyarteritis nodosa
• Immunologic issues• Sarcoidosis, Crohn’s, PBC,
Histiocytosis X• Leukocyte oxidase defects
• CGD• Hypersensitivity pneumonitis
• Farmer’s lung, bird fanciers• Chemicals
• Talc, Silica, Zirconium• Malignancy
• carcinoma
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Granulomatous Inflammation• Infection
• Fungi• Histo, cocci, blasto, sporothrix,
aspergillus, crypto• Parasites
• Toxo, Leish, schistosomiasis• Spirochetes
• T. pallidum• Mycobacteria
• M. tuberbulosis, M. leprae, M. kansasii, M. marinum, M. avian
• Bacteria• Brucella, Yersinia, Bartonella,
Nocardia, Actinomyces• Misc
• Whipple’s disease, Kikuchi (?)
• Vasculitis• Granulomatosis with
polyangiitis, Churg-Strauss, GCA, SLE, polyarteritis nodosa
• Immunologic issues• Sarcoidosis, Crohn’s, PBC,
Histiocytosis X• Leukocyte oxidase defects
• CGD• Hypersensitivity pneumonitis
• Farmer’s lung, bird fanciers• Chemicals
• Talc, Silica, Zirconium• Malignancy
• carcinoma
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Many syndromes more to consider….• Rheumatoid arthritis• Thyroiditis• Allergic alveolitis• Hemophagocytic syndrome• IBD• Pheochromocytoma• TTP/HUS• Body cavity lymphoma, primary effusion lymphoma• Multicentric Castleman’s Disease• Drug eruption• Lymphoma/leukemia• Vasculitis