Grand rounds 8/15/2017

Case 1 : Ulceroglandular tularemia associated with Feline Tularemia

68 yr old presented with fevers for 2- 3 weeks and increasing pre-auricular, and submandibular painful lymphadenopathy. He had two cats, one recently passed away. He remembered that the cat had a febrile illness and the patient sustained several scratches prior to his illness.
Francisella turarensis antibody returned positive 1:1280

1.  The incidence of tularemia is mostly centered in midwest US with highest numbers reported in Missouri (19%), Arkansas (13%), and Oklahoma (9%).  Subspecies tularensis (Jellison Type A) is the most virulent subspecies of Francisella tularensis and is the primary subspecies found in North America. There are six clinical tularemia syndromes defined by site of inoculation and presentation. The ulceroglandular and glandular forms are the two most common types in North America . Oropharyngeal,oculoglandular and typhoidal forms are less common.  Of 106 Francisella tularensis isolates, mostly from Nebraska, collected during 1998–2012: 48% of   cases were feline-associated.

2. The most common confirmatory study for tularemia is the microagglutanin test using antibody titers which develop about two weeks after incident infection. A one-time titer of 1:160 or a four-fold increase in titers from serums taken two weeks apart are considered diagnostic.

3.The WHO recommends using the bactericidal antibiotics  gentamicin for 10 days or bacteriostatic antibiotic doxycycline for 14 days

The patient above had a good response to oral doxycycline.


Case 2: Varicella Zoster meningoencephalitis 

65 yr old with myasthenia gravis presented with right ear pain and headaches and subjective fevers. She was on 40 mg of prednisone two days a week. She was febrile to 38.2C and had small vesicular lesions on her right external ear and one vesicular lesion on her right knee and L1 dermatome.

CSF examination revealed 329 WBC's (91% Lymphocytes), Protein74 and glucose of 57. CSF VZV PCR was positive
 1. Involvement of the CNS with cutaneous herpes zoster is probably more common than recognized clinically.  A rare manifestation of CNS involvement by herpes zoster is granulomatous cerebral angiitis, which usually follows zoster ophthalmicus. Rash is usually present but not always before the CNS disease.
2. Zostavax   developed specifically for protection against herpes zoster contains higher  plaque-forming units (PFU) per dose, compared to chickenpox vaccines . Although contraindicated in patients with immunecompromise as it is live vaccine - it could be considered in patients ≥50 years old who are receiving therapies that induce low levels of immunosuppression ( prednisone < 20 mg / day).

AUGUST 8, 2017 GRAND ROUNDS

CASE 1: DISSEMINATED HISTOPLASMOSIS

43/M with rheumatoid arthritis (receiving methotrexate and etanercept), p/w chronic pneumonia; additional studies showed an elevated urine Histoplasma antigen and a GMS stain of a bronchoalveolar lavage that demonstrated numerous yeasts forms consistent with Histoplasma

1. Histoplasmosis is the most common invasive fungal infection among people receiving anti-TNF therapy.

2. Anti-TNF therapy should be discontinued in patients who develop histoplasmosis.

3. Be aware of immune reconstitution syndrome (IRIS) in patients with histoplasmosis while receiving effective antifungal therapy (in 9% of cases). This occurs after anti-TNF medication is discontinued.

CASE 2: DISSEMINATED PARVOVIRUS B19 INFECTION

57/M w/ primary biliary cirrhosis s/p liver transplantation 11 years prior (receiving tacrolimus and mycophenolate), p/w chronic fatigue and new-onset pancytopenia (Hgb 6.6, WBC 1.9, platelet 65); additional studies showed low reticulocyte count and a positive blood parvovirus B19 PCR test

1. Suspect parvovirus B19 in immunocompromised patients with:

·         Unexplained anemia (seen in 99% of patients) or pancytopenia

·         Clinical syndromes: fever (25% of patients), rash, arthralgia

·         Others: hepatitis, myocarditis, pneumonitis, neurologic manifestations, vasculitis

2. Two-thirds of infection occurs within 3 months after transplantation (can be late as well).

3. The diagnosis commonly rests on detecting a positive serum parvovirus Ig M (in 75% of transplant patients) or PCR. If both tests are negative but the suspicion remains, a bone marrow biopsy can be done and this normally shows characteristic giant pronormoblasts.

4. IVIG 400 mg/kg/day for 5 days is the treatment of choice. It can recur in 28% of transplant patients even after therapy. 

JULY 25, 2017 GRAND ROUNDS

CASE 1

21 year old previously healthy male w/ fever, cough, sore throat, and acute numbness of the left side of the face; CXR showed left lower lobe cavity and head CT demonstrated a right parietal lobe abscess; blood culture grew Fusobacterium necrophorum (Lemierre’s syndrome)

1. Lemierre’s syndrome is an infectious thrombophlebitis of the internal jugular vein that is notorious for causing septic embolization to the lungs (97%; which can appear as a cavity, an infiltrate, abscess, or empyema), brain, bone and joint. 92% of cases are caused by Fusobacterium.

2. It should be suspected in patients with a prior history of pharyngitis and now p/w fever and septic embolization (“an infectious embolic disease similar to infective endocarditis”).

3. Prolonged antibiotics is required (usually 4 weeks). The use of anticoagulation is controversial but is usually beneficial if thrombosis continues to progress despite antibiotic therapy. Ligation of the jugular vein is reserved for patients with persistent sepsis despite antibiotics.

CASE 2

A 12 week old term infant w/ 6 weeks of fever and diffuse interstitial nodular opacities on CXR; exam: 1^st percentile for weight/length, hepatosplenomegaly; BAL showed Pneumocystis jirovecii on stain and Histoplasma capsulatum on fungal culture; urine Histoplasma antigen was highly positive; immunodeficiency work-up showed pan-T cell lymphopenia that were naïve and thymic-derived; suspected to have dyskeratosis congenital

1. High yield facts about dyskeratosis congenita:

•       Mutation in a variety of genes involved in telomere lengthening/protection
• I     Inheritance: recessive (X-linked or autosomal), autosomal dominant
•       Can be seen in adults: median age of diagnosis is 15 years but the range of presentation is wide (birth to 75 years)
•       Classic triad (ABSENT in the neonatal period but seen in <50% of older patients and ¾ of cases will have at least 1): abnormal skin pigmentation (reticular hyperpigmentation in the neck/chest), nail dystrophy, oral leukoplakia
•           Complications: bone marrow failure (50% by age 50), immunodeficiencies (lymphocyte subset most prone) à most common cause of death; others: pulmonary fibrosis, head/neck squamous cell carcinoma, myelodysplastic syndrome
•       Treatment: bone marrow transplant (for bone marrow failure), androgen therapy

CASE 3

78 previously healthy male from Fairport, New York, p/w fever and chills for 10 days; labs showed anemia (Hgb 10.7), thrombocytopenia (58,000), and mildly elevated liver enzymes; other w/u showed a haptoglobin < 1 and an elevated LDH; smear showed evidence of babesiosis (3% parasetemia) and Babesia microti PCR was detected

1. Suspect babesiosis in patients you suspect to have tickborne illness (fever, elevated transaminases, and thrombocytopenia). It is transmitted through the bite of the deer or blacklegged tick Ixodes scapulars.

2. Ixodes scapularis also transmits: Anaplasma, Borrelia burgdorferi (Lyme disease), and Powassan virus type II.

3. Babesiosis can by asymptomatic (made manifest only during splenectomy or w/ development of an immune compromising condition), mild (this can be self-limited), or severe. Hemolytic anemia is the principal clue in a lot of cases (“think, malaria w/o a history of travel to malaria-endemic areas; the trophozoite/merozoite forms in the blood can look like malaria).

4. Typically has long incubation period after a tick bite (up to 3 months; typically 1-6 weeks) and even longer after blood transfusion (up to 6 months; typically 1-9 weeks).

5. Co-infection w/ Anaplasma or Lyme sometimes occurs. Hence, suspect concurrent babesiosis in patients who don’t respond to therapy for Anaplasma or Lyme. Diagnosis is through blood smear and PCR testing.

6.Treatment:

• Asymptomatic parasetemia requires treatment to prevent transmission and progression to disease especially in immunocompromised patients.
• Mild: atovaquone + azithromycin
• Severe (e.g. >4% parasetemia): clindamycin + quinine; consider exchange transfusion
• Duration: 7-10 days for immunocompetent patients; at least 6 weeks or up to 2 weeks after parasites are no longer present on smear (whichever is longer) for immunocompromised hosts

7. Rapid review of ticks (for more information, click here):

• Ixodes scapularis (Eastern, northern Midwest): as mentioned above
• Ablymoma americanum (lone start tick; Midwest, Southern, southeastern): Ehrlichia, Heartland, southern tick-associated rash illness (STARI), tularemia, Bourbon (? maybe)
• Dermacenteor variabilis (American dog tick; eastern, south central, Pacific coast): RMSF, tularemia
• Dermacentro andersoni (Rocky Mountain wood tick; west of Mississippi, Pacific coast): RMSF, tularemia, Colorado tick fever