Bronchiectasis, sinusitis and obstructive azoospermia who have no evidence of cystic fibrosis
Primary Ciliary Dysfunction
Allergic bronchopulmonary aspergillosis
should be suspected in patients with a long history of asthma that is resistant to bronchodilator therapy and associated with a cough often productive of sputum that is mucopurulent or contains mucous plugs.
Thanks to Dr. Szumowski for sending us the case of a middle aged man who presented with acute L knee swelling and pain one week after a viral URI syndrome, initially concerning for septic joint. His clinical course was complicated by recurrent high daily fevers, a diffuse maculopapular rash, and knee arthrocenteses and joint washes that were clean leading to a diagnosis of Still’s disease!
Still’s disease is a diagnosis of exclusion! Yamaguchi criteria can help with ruling in the diagnosis.
Still’s remains a multi-systemic disorder of unknown etiology because it’s difficult to diagnose and rare (0.16 cases per 100,000).
RF and ANA are generally negative but can be positive in <10% of patients with Still’s in low titers.
~66% of patients present with sore throat secondary to cricothyroid perichondritis or aseptic nonexudative pharyngitis.
The disease is often recurrent. Predictors of poor outcome include erosive polyarthritis on presentation and shoulder/hip involvement.
Described in 1897 by George Still, it is a systemic inflammatory disorder of unknown etiology
Some clarifications on nomenclature:
Systemic juvenile idiopathic arthritis (sJIA): first presentation <17 years old, previously referred to as Still’s disease
Adult onset Still’s disease (AOSD): first presentation > 17 years old
Epidemiology of AOSD:
0.16 cases per 100,000
No sex predominance (F=M)
Bimodal age distribution with peak between 15-25 and another 36-46 years of age. New diagnosis in patients >60 have been reported.
Poorly understood but likely a combination of genetic predisposition, environmental triggers (viruses such as echo, coxsackievirus B4, mycoplasma, yernisnia, lyme, etc), activated innate immunity leading aberrant production of pro-inflammatory cytokines
High ESR and CRP
Very high ferritin levels
Ultimately a clinical diagnosis so it’s important to exclude potential mimickers
Yamaguchi criteria are the most sensitivity (93.5%)
Fautrel’s Criteria are the most specific (98.5%)
Largely empirical since clinical trial data is lacking
High dose steroids are first line when systemic symptoms predominate
MTX is second line
NSAIDs are not good
Biologic agents for refractory cases (IL1 antagonist anakinra or canakinumab), IL6 antagonist tocilizumab, or TNF inhibitors.
Monocyclic pattern (systemic single episode)
Polycyclic pattern (multiple episodes, usually <1 /year)
Chronic pattern (persistently active disease with poly arthritis)
Thanks to the Human Dx Project for providing us with this fascinating case of a middle aged woman with history of asthma who presented with acute onset of fever and epigastric abdominal pain as well as a chronic progressive cough, found to be febrile, tachycardic, and ill appearing, with E coli bacteremia of unknown source. Further history taking revealed a similar hospitalization several months prior with idiopathic E coli bacteremia. Strongyloides titers were sent and markedly elevated. She was treated with ceftriaxone and ivermectin and made a full recovery.
Absence of eosinophilia does not rule out strongyloides. Keep in mind that those presenting with severe illness and hemodynamic instability are commonly in a high cortisol state which can lead to eosinophil apoptosis. Also, in those with history of steroid use (even for short periods of time), eosinophil count can be negative.
Think of strongy in anyone with the right travel history, older age, malnutrition, HIV, or steroid use.
Signs and symptoms can be quite non-specific so a high index of suspicion is required to make the diagnosis.
Think of strongyloides in a patient with history of recurrent GNR bacteremia of unknown etiology!
Higher incidence noted going from yellow to orange to red on the map above
Typically in travelers to endemic areas, immigrants from endemic regions, or anyone with barefoot contact with infested soil.
Risk factors include older age, malnutrition, HIV, and steroid use
Signs and symptoms
Infected people can be asymptomatic or minimally symptomatic for years:
Could also have mild waxing and waning GI, skin, or pulmonary symptoms for years
Eosinophilia without symptoms
Skin: urticarial, larvae currens (see picture below), angioedema, erythroderma
Pulmonary: chronic cough, hemoptysis, recurrent pneumonia, astham that gets worse with steroids
Credit goes to Dr. Scott Burns from Roper Hospital in Charleston for his case on the Human Diagnosis Project.
Today we discussed a case of a young man with otherwise no medical history presenting with subacute dry cough, malaise, and weight loss. On exam he was septic on presentation with notable oral thrush. CXR revealed bilateral interstitial infiltrates and a RUL cavity with air fluid level which was confirmed on CT. LDH was elevated. He was confirmed HIV positive with a low CD4 count in the single digits, and BAL confirmed the diagnosis of PCP/PJP pneumonia!
Oral Thrush: NEVER assume normal, extremely rare in immunocompetent patients, so if you see this, consider whether the patient could be immunocompromised.
Cavitary Lung Lesion DDX
Bacterial: Legionella, rhodococcus
Fungi: PCP/PJP, mucormycosis, blasto
HIV with CD4 < 200
BMT, organ transplant patients
Rarely occurs in immunocompetent patients
Typically subacute onset of pulmonary symptoms, non-productive cough, fever chills, malaise, SOB
Might have other clues of immunocompromised status
CXR: Classic description is bilateral interstitial infiltrates
We recently had a case of a middle age man with SLE on chronic prednisone, ESRD on PD, presenting with acute on chronic shoulder pain x 10 days. Presentation was initially concerning for septic arthritis, and joint washout revealed gross purulence from the shoulder joint. Cultures were sent but no additional fluid studies were obtained.
A subsequent TTE, and later a TEE, confirmed a mitral valve vegetation concerning for concurrent infective endocarditis. However, multiple sets of blood cultures, fungal cultures, synovial fluid culture from the initial I&D/wash out, and even 16S PCR of the synovial fluid were all negative. This is a rare case of culture negative endocarditis which is later thought to be more likely Libman Sacs!
Risk factors: Advanced age, pre-existing joint dz, recent surgery or injection, SSTI, IVD, indwelling catheter, immunosuppression.
Most cases arise from hematogenous seeding, hence bacteremia is common.
Direct inoculation: usually due to trauma, surgery/injections, or wounds.
Usually mono-microbial, and Staph aureus is the most common cause of septic arthritis in adults.
GNR can be seen in older adults or in immunocompromised patients
Monoarthritis is most common
Edematous, painful, warmth, limited ROM
Older patients may not be febrile
20% of cases can present as oligoarticular or polyarticular infection. Polyarticular septic arthritis is more likely to occur in pts with RA
Most common affected joint is the knee
Could be a manifestation of infective endocarditis, esp amongst IVDU
Synovial fluid analysis and culture, should be obtained prior to abx
Positive gram stain or culture is gold standard and diagnostic
PCR only required in rare cases since most non-gonococcal cultures obtained prior to antibiotics return positive. Negative cultures can result due to recent abx or atypical organism.
In pts with purulent synovial fluid (WBC 50k-150k) but culture negative, a presumptive dx can be made.
Likelihood of septic arthritis inc with inc leukocyte count
Blood cultures should be obtained
Should also evaluate for endocarditis given most common organism is staph aureus
Always get a radiograph to evaluate for concurrent bone/joint involvement
CT/MRI can be useful if looking for an effusion
Viral (usually polyarticular), i.e. Zika, Dengue, chikungunya, parvo, rubella, adenovirus
Joint drainage, severe infectious may require repeated aspiration or even wash out.
Most cases are staph, MRSA cases on the rise
Suspect pseudomonas if pt is immunocompromised or has h/o IVDU
Intra-articular abx: typically not used
Staph aureus with bacteremia: At least 4 weeks
Staph aureus without bacteremia: at least 14 days IV, followed by 1-2 weeks PO
Bone involvement: 4-6 weeks
Any organisms, any bone involvement: 4-6 weeks
Other organisms: Typically at least 4 weeks
Culture Negative Endocarditis
Definition: Endocarditis without an identified organism in at least 3 independent blood cultures with negative growth after 5 days
2-7% of IE cases
3 most common causes:
Atypical organisms (fastidious bacteria i.e. zoonotic microbes, fungal)
Thanks to Dr. Olivia Lee for letting us know of the case of this middle-aged woman with h/o endometrial cancer s/p TAH/BSO who was BIBA on a 5150 for GD after being found living in her yard. Her medical clearance work up led to the diagnosis of endocarditis with a large abscess on the mitral valve leading to septic emboli to the brain, spleen, and kidneys as well as vitritis and endophthalmitis. She was also noted to have an indwelling mediport with a vegetation at its tip, showering emboli into her lungs. She successfully underwent urgent surgical replacement of her infected/destroyed valve.
Use Duke’s criteria to help with your pre-test probability of endocarditis. If patient meets criteria for definite endocarditis, consider going straight to a TEE.
TTE is not sensitive but highly specific for endocarditis. However, in a patient with concerning clinical features (see next bullet point), a TEE is necessary to evaluate valve condition and plan for surgical intervention. TTE is more useful if pre-test probability of endocarditis is low.
Indications for surgery
Valve dysfunction causing heart failure
Perivalvular extension with development of abscess, fistula, and/or heart block
Fungi or other highly resistant organisms that are difficult to treat with abx alone
Persistent bacteremia despite maximal treatment
Recurrent embolization with persistent vegetations
Large vegetations (>1 cm) with severe valvular regurg
S aureus prosthetic valve endocarditis
Indications for earlysurgery:
Prevention of embolic events
Most common cause of death in endocarditis is heart failure.
For a thorough review of endocarditis, please see our previous blog post here.
Some key learning points from our M&M case discussion today:
Ertapenem is a slow acting antibiotic and not an ideal empiric treatment in a patient who presents with sepsis or is acutely ill. So if you want to use a carbapenem for empiric coverage, pick meropenem or imipenem instead.
Fun fact: ertapenem is actually more expensive than mero/imi. The only use for ertapenem is in transitioning patients from hospitalization to home where its daily dosing is more favorable than the TID dosing of meropenem.
For diabetic foot ulcers, please refer to our SCVMC algorithm to help you figure out empiric antibiotics. Simply open the HHSConnect browser and type in diabetic foot in the search bar to pull up the algorithm.
If blood cultures take a longer time to speciate (in our patient, over 5 days), expect anaerobes because anaerobes are difficult to culture and are sent out for speciation. E coli is an organism that should speciate quickly and would grow in aerobic and anaerobic bottles. If a species is only growing in anaerobic bottles, then it’s probably not E coli.
Levofloxacin is the only fluoroquinolone that has a role in outpatient treatment of GNR bacteremia, other fluoroquinolones (like cipro) are less effective.
Avoid using fluoroquinolones for empiric treatment of E coli bacteremia or pyelonephritis because our VMC antibiogram shows ~25% resistance with fluoroquinolones.
A 42yo homeless man with AIDS not on ART with CD4 < 10, VL 440K+, presents with an acutely enlarging right-sided neck mass that was tender and firm, with associated fevers and malaise… Blood CrAg returned positive, and biopsy revealed encapsulated yeast with narrow based buds…
Yep, you’ve guessed it, it’s crypto!
Invasive fungal species, primarily C neoformans and C. gattii are seen, found world wide in soil. Associated with infections in immunocompromised hosts.
AIDS (AIDS defining illness)
Long term steroids
Solid organ transplantation
Most of the population have been exposed to the spores of C. neoformans, and in immunocompetent patients, most cases are asymptomatic to mild symptoms.
Typically inhaled and affects the lungs first, and then can disseminate to CNS (most feared), skin, solid organs, bones, etc
CNS: Feared, no-specific sx of fever, AMS, headache.
Disseminated disease requires at least 2 non-contiguous sites
Culture is definitive
GS: Encapsulated budding yeasts with narrow based buds on India Ink = characteristic
IF e/o dissemination, get CXR, urine, LP, blood cultures
Cryptococcal capsular antigen (CSF or blood) are > 90% sensitive and specific.
Cr titers correlate with organism burden and prognosis, but not helpful to follow during treatment and doesn’t correlate with tx response. Titers > 1:512 is associated with poor prognosis.
CSF or blood CrAg is diagnostic
Mild to moderate in immunocompetent hosts: Fluconazole for 6-12 months.
Alternatives are itraconazole, voriconazole, or posaconazole.
Immunocompromised hosts with mild-moderate pulmonary disease in the absence of diffused pulm infiltrates, CNS, or disseminated infection, can use fluconazole 6mg/kg (typically 400mg) daily for 6-12 months, with similar alternatives if fluconazole is not available/tolerated.
Immunocompromised hosts with severe disease or CNS infection: ARDS occur frequent in IC patients with cryptococcal pneumonia.
Induction: Ampho B + flucyotosine for minimum of 2 weeks.
Consolidation: Fluconazole 200-400mg daily x 8 weeks
Maintenance therapy is continued for at least 1 year.
Intracranial pressure control: Cryptococcal meningoencephalitis patients might need daily LPs to relief ICP, might require VP shunt. Do not use mannitol or acetazolamide.
Steroids not shown to be helpful.
ART: Usually not started with induction therapy due to a risk of IRIS.
ART is usually started 2-10 weeks after antifungal therapy has been started to minimize risk.
Today, we talked about the case of a middle-aged man from the Philippines who presented with a one year progressive pruritic rash involving the face, arms, and legs as well as a distal symmetric peripheral neuropathy, found to have lepromatous leprosy on skin biopsy!
Mycobacterium leprae and lepromatosis like to grow in cooler areas, so infection often manifests in the skin and the peripheral nerves.
Transmission is likely via respiratory route, through broken skin, and by touching armadillos!
Early recognition and treatment is important to prevent injury to peripheral nerves.
DDx for rash + neuropathy
Lyme (usually cranial nerves, radiculopathy)
Zoster (tends to be painful rather than pruritic and localized to a dermatome)
WNV (flaccid paralysis)
Our patient presented with a pruritic rash and largely a distal symmetric peripheral neuropathy. We generated the following Venn diagram in report to help us with the diagnosis:
AKA Hansen’s disease
Infection caused by mycobacterium leprae and mycobacterium lepromatosis, separate species that cause similar clinical disease. They are both obligate intracellular parasites.
Involves the skin and peripheral nerves
Early treatment is important to prevent involvement of the eyes, hands, and feet due to neuropathy. The neuropathy is often non-reversible.
205 new cases detected in the US in 2010. 75% among immigrants (most commonly India, Brazil, Indonesia, Bangladesh, and Nigeria)
Unknown but probably respiratory route especially in lepromatous leprosy. Sometimes can transmit through broken skin. Also from armadillos.
Most people do NOT develop disease after exposure. Risk factor for disease development include older age, genetic influences, and immunosuppression.
Grows in cooler areas
Described in categories pertaining to how much bacillary burden of disease is present with tuberculoid being the least amount and lepromatous having the highest disease burden.
Hypopigmented or reddish patches on the skin
Typically involve the earlobes with nodular thickening and distributed symmetrically on the body in lepromatous leprosy.
Diminished sensation or loss of sensation within skin patches
Paresthesias of hands/feet
Neuropathy occurs early in disease course
Painless wounds or burns on the hands or feet
Lumps or swelling on the earlobes or face
Tender, enlarged peripheral nerves
Late findings in disease course:
Weakness of the hands with claw fingers, foot drop, facial paralysis, lagophthalmos (can’t close eyes completely due to CN7 palsy), lack of eyebrows/eyelashes, collapsed nose, perforated nasal septum.
Intermittent bacteremia can lead to focal lesions in various organs (liver, bone marrow, testicles and larynx)
Consider it in patients with skin lesions and/or enlarged nerve(s) accompanied by sensory loss.
No reliable blood or skin tests available.
Usually clinical and skin biopsy
Goal: Prevent and/or minimize injury to peripheral nerves!
Often times it’s loss of sensation but later can progress to painful neuropathy
Dapsone plus rifampin for tuberculoid leprosy. Clofazimine is added for lepromatous leprosy.
Duration can be up to 24 months
Treat neuritis with steroids for a prolonged course
Make sure to screen for G6PD deficiency before prescribing dapsone
Monitor liver function with rifampin
Clofazimine (causes phototoxicity) is not available in US pharmacies and must be obtained from the NHDP.
May take a few years for skin lesions to resolve completely with treatment
Very curable, low relapse rates, typically no drug resistance
We worked through a case from the Human Diagnosis Project with a 57 yo M originally form Guatemala (moved to US 25 years ago) with a history of pre-DM and recently diagnosed and treated Lyme disease presenting with 2 months of persistent fever, chills, malaise, and myalgias. He received extensive work up, and everything turned (including TEE, LP, SPEP, rheum, BM biopsy, HIV) were negative. He had splenomegaly on exam, and CT CAP revealed hilar LAD + LLL tree-in-bud along iwth a 20cm spleen. The patient was ultimately diagnosed with DLBCL, AND cryptococcal pneumonia secondary to immunosuppression from his lymphoma!
Credit: Dr. Ron Cho, New York Medical College, Internal Medicine.
Fever of Unknown Origin
Fever > 38.3 °C on multiple occasions
Duration > 3 weeks
Uncertain diagnosis after 3 outpatient visits or 3 days in the hospital (revised, used to be 1 week inpatient investigation) or 1 week of “intelligent and invasive” ambulatory investigation
TB is the single most common infection in most FUO series, can be extrapulmonary, military, or pulmonary. May occur concurrent in AIDS patient, leading to a more subtle presentation.
Bacterial endocarditis (2-5% of these are culture negative bacterial endocarditis, i.e. from Coxiella brunetii and tropheryma whipplei).
Super rare causes of endocarditis with difficult to grow culture: Mycoplasma, Legionella, Bartonella, Brucella, HACEK organisms
TEE is positive in > 90% of cases of FUO from infective endocarditis.
Viral i.e. EBV
Malignancy: Most common are lymphoma and leukemia.
Systemic Rheumatic disease
Adult onset Still’s disease: young and middle age adults, daily fevers, arthritis, evanescent rash.
Factitious fever: Psych, predominantly affects F and healthcare professionals
Disordered heat homeostasis after a stroke or from hyperthyroidism
Multiple concurrent infections
Hereditary periodic fever syndromes
Unidentified: 19% of cases are unidentified.
Get a detailed history, including fever pattern exposure history, sexual history, family history, medications.
Do not start empiric therapy unless pt is neutropenic or unstable, or you have a high-suspicions for GCA or culture negative endocarditis.
Most common type of NH Lymphoma, representing 25% of cases
Median age: 64, 55% men. Also accounts for 25% of childhood NHL.
Caucasians at higher risk and esp patients of Swedish and Danish ancestry
Other risk factors: HIV, h/o radiation or chemotherapy
Heterogenous group of tumors that arise from mature B cells in (90% of cases, the other 10% from T cells)
Most common mutations found in DLBCL:
BCL6 gene mutation
Nodal and extra-nodal manifestation at time of diagnosis. Most common extra-nodal manifestation is bonemarrow or GI tract.
Typically pts present with a mass, most commonly in the neck, abd, or mediastinum but it can manifest anywhere.
Painless LAD might be present in 2/3 of cases.
Less than 50% will have B-sx.
Can present with pancytopenia. Might see elevated LDH, uric acid, and calcium.
Excision LN or tissue biopsy, excisional LN is preferred
Ann Arbor Criteria
Stage I – disease in single lymph node or lymph node region.
Stage II – disease in two or more lymph node regions on same side of diaphragm. Note: Stage II contiguous means two or more lymph nodes in close proximity (side by side).
Stage III – disease in lymph node regions on both sides of the diaphragm are affected.
Stage IV – disease is wide spread, including multiple involvement at one or more extranodal (beyond the lymph node) sites, such as the bone marrow (which is involved commonly), liver, pleura (thin lining of the lungs).
Spleen is considered nodal
1st line is RCHOP (3 cycles) and local regional radiation, 6-8 cycles of R-CHOP is an acceptable alternative.
Emerging data, DA-EPOCH is better for younger patients < 60 yo and with certain phenotypes
Double Hit Lymphoma: Lymphoma resembling DLBCL but has MYC gene translocation AND rearrangement of BCL 2 or BCL 6. RCHOP still first line but overall prognosis is worse. DA-EPOCH-R might work better.