PGY3 George Samaan presented a very interesting case of a 22 year old M who presented with 2 months of polyarthralgias and a full body rash. Physical exam was significant for multiple violaceous plaques and nodules over the face, chest and back, with tenderness to palpation over multiple joints but no evidence of erythema, swelling or synovitis.
The differential for polyarthralgias is broad and includes infectious, reactive arthritis, rheumatoid arthritis, systemic rheumatic disorders (lupus, vasculitides, Still’s disease, sarcoidosis).
Work up for infections and rheumatologic disorders were negative, including ANA, RF/anti-CCP, anti-streptolysin, ANCA, HIV, Hepatitis B/C. The patient eventually received a skin biopsy which showed Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN), and patient’s diffuse joint pain was thought to be due to paraneoplastic arthritis. BPDCN is a rare hematologic malignancy that commonly manifests as cutaneous lesions. Malignant cells can be detected in peripheral blood in ~60% of case, however the number of circulating cells is variable and may not be detected. Similarly although bone marrow involvement occurs in ~80% of cases, it may be difficult to identify the malignant cells. Diagnosis should be suspected in those presenting with brown/violaceous bruise-like lesions, and skin biopsy is necessary.
Thank you George for presenting this interesting and rare case, and for reminding us that unusual skin lesions without clear etiology may be the presenting sign of an occult malignancy!
Thank you to PGY2 Shawn Shah for presenting an interesting case of a 66 year old homeless male who presented with fevers, productive cough, and chronic intermittent chest pain. The patient had a transthoracic echocardiogram done which showed an EF of 35%, as well as a 1.6×1.4cm aortic valve vegetation. The patient had repeatedly negative blood cultures and culture-negative endocarditis was suspected.
What is culture negative endocarditis? -3 negative blood cultures (after 5 days of incubation) **Remember that administration of antibiotics before obtaining blood cultures decreases the recovery rate of bacteria by 35-40%!!! -HACEK organisms previously thought to be the most common causes, however can be easily isolated when cultured fro more than 5 days -Certain exposures/conditions can point to a specific diagnosis such as: farm animals (Brucella, Coxiella), homeless shelters (bartonella quintana), cats (Bartonella henselae), unpasteurized milk (Brucella/Coxiella) -Immunocompromised and HIV+ patients are at risk for fungal and Coxiella endocarditis
Remember to consider causes of noninfective endocarditis as well such as anti-phospholipid antibody syndrome (sterile valvular vegetations, most commonly affecting the mitral valve), atrial myxoma, marantic endocarditis
Empiric Therapy -ID consult is recommended for the empiric therapy of culture negative endocarditis. -For acute presentations of native valve endocarditis (NVE), coverage for Staph aureus, beta-hemolytic strep and aerobic gram negative bacilli should be initiated (vancomycin + cephalosporin) -For subacute presentations of NVE, coverage for Staph aureus, viridans group strep, HACEK and enterococci should be initiated (vancomycin + ampicillin-sulbactam). **These regimens do not cover organisms for all organisms that cause culture negative endocarditis. If other organisms suspected, need additional coverage such as Doxycycline.
The patient was subsequently found to have elevated Bartonella titers and had an aortic valve replacement surgery performed, with the native valve staining positive for Warthin-Starry stain (supportive of Bartonella). Treatment for confirmed Bartonella endocarditis: Doxycycline + Gentamicin (Rifampin if cannot use gentamicin) for 14 days. If valve surgery is performed, doxycycline alone is continued for 6 weeks. If surgery is not performed and infected tissue is still present, doxycycline is continued for 3 months.
On a semi-related note, check out the POET trial (https://www.nejm.org/doi/full/10.1056/NEJMoa1808312) which discusses the use of partial oral antibiotics in the treatment of left sided endocarditis. We will be discussing this in journal club on December 20th!
Today we presented a case of a 44 year old M with no significant past medical history who reported a 3 month history of shortness of breath and abdominal pain and distension. Given the history and physical exam findings consistent with a volume overloaded state, the initial differential diagnosis included causes of heart failure, liver disease and renal disease (ESRD, nephrotic syndrome). Labs were significant for an infiltrative pattern of liver injury (significantly elevated alkaline phosphatase, minimally elevated transaminases and normal bilirubin) as well as an elevated globulin gap of 4.8. TTE showed reduced an ejection fraction of 35% and abdominal ultrasound demonstrated cirrhosis and ascites.
Work-up of an elevated globulin gap:
– An elevated globulin gap (difference between the total serum protein and serum albumin concentration) should always be evaluated. The first step in evaluation is to determine whether it represents a monoclonal or polyclonal gammopathy.
– Causes of polyclonal gammopathy include viral infections (acute HIV, hepatitis C), connective tissue disorders and other causes of persistent inflammation (acute phase reactants will cause an increase in the globulin gap).
– Causes of monoclonal gammopathy include MGUS, multiple myeloma, Waldenstrom’s macroglobulinemia, amyloidosis and lymphoma.
– An SPEP (shown below), immunofixation and free light chain assay should be ordered to help determine the etiology of the protein gap. Remember that SPEP is the initial screening test and the sensitivities of serum immunofixation and free light chain assay are higher for detecting the presence of paraproteins. An abnormal free light chain ratio indicates overproduction of either kappa or lambda light chain.
Our patient’s SPEP/serum immunofixation showed a monoclonal gammopathy (IgG/Lambda, 2.4 g/dL) and the kappa/lamda free light chain ratio was decreased. This raised concern for MGUS (M protein <3g/dL, bone marrow plasma clonal cells <10%, asymptomatic and lack of *CRAB criteria). However in the setting of multiple organ involvement (cardiac, liver), a diagnosis of amyloidosis was considered more likely. The patient subsequently had an abdominal fat pad biopsy, a liver biopsy and a right ventricular biopsy which all demonstrated AL Amyloidosis.
*CRAB: hypercalcemia, renal involvement, anemia, bone disease