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EDITORIAL Adam J. Brown, MD Department of Rheumatologic and Immunologic Disease, Cleveland Clinic, Cleveland, OH; Author of Rheumatology Made Ridiculously Simple; Host of the podcast Rheuminations Famous and not-so-famous physical fi ndings in infectious endocarditis: A look back f you’re looking for a disease that is the ■ OSLER’S CONTRIBUTIONS I most quintessentially archetypal of inter- The understanding of endocarditis evolved nal medicine, it’s diffi cult to surpass infectious rapidly after the disease was put into the fore- endocarditis. front of medicine by Dr. William Osler in Gathering a thorough history, pushing and 1885. Then came advances in microbiology prodding a patient’s spleen, pulling down the like the introduction of blood cultures, al- skin under the eyes to look for petechiae, hov- lowing for more rapid and accurate diagnosis. ering your face within inches of an open palm Once the diagnosis of endocarditis became searching for a cutaneous clue to an infectious more established, clinicians began recogniz- bomb dangling on the leafl et of the mitral ing subtler clues that we apply at the bedside valve—what is more emblematic of internal today. Osler was medicine? Osler placed endocarditis on the medical map with his Gulstonian lecture series on the the fi rst See related article, page 310 subject in 1885.1 Before these lectures, infec- to synthesize tive endocarditis was a known entity, usually The physical examination fi ndings of in- the known data diagnosed at autopsy, but no comprehensive fectious endocarditis are storied and known information existed on its presentation and and case by heart by every medical student who can natural course. Osler was the fi rst to synthe- reports on rattle off Osler nodes, Janeway lesions, size the known data and case reports at that and splinter hemorrhages without a smart time, presenting it in a cohesive way to better endocarditis phone in sight, although they may mix up understand the condition. He recognized im- in a lecture which one of those lesions is painful. These portant aspects of the disease, noting the wide series in 1885 fi ndings, though famous, are rare, and the range of clinical presentations, the progres- more common fi ndings like splenomegaly sion from an acute febrile illness leading to and subconjunctival petechiae are less read- rapid deterioration and death. He also noted ily listed. that the illness could present over months to The report by Goff et al in this issue is a years before death, what would later be called great example of the many unusual ways in- subacute bacterial endocarditis. fectious endocarditis can present. Osler also recognized that valvular abnor- To better appreciate the famous and not- malities predisposed patients to endocarditis, so-famous physical examinaton fi ndings of and that a history of rheumatic fever was com- infectious endocarditis, it’s important to look mon. Osler gave credit to Ontario physician Dr. back at the evolution of the disease. J. A. Mullin for pointing out these lesions, but in 1913, Dr. F. Parkes Weber ascribed the fi nd- 2 doi:10.3949/ccjm.88a.21033 ings to Osler. 316 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 88 • NUMBER 6 JUNE 2021 Downloaded from www.ccjm.org on September 30, 2021. For personal use only. All other uses require permission. BROWN ■ JANEWAY’S CONTRIBUTIONS ■ LIBMAN’S CONTRIBUTIONS In 1899, Dr. Edward Janeway described painless Libman was a key fi gure in elucidating the lesions on the palms and soles in patients suf- more common signs and symptoms of endo- fering from endocarditis. His objective in de- carditis, as well as introducing blood culture as scribing these lesions was a viable way for clini- a diagnostic tool in the United States.8 cians to differentiate endocarditis from another Libman was an American physician who “malignant process” presenting with fever and studied microbiology in Graz, Austria, before weight loss. He described the lesions as “small returning to the United States to work at Mt. hemorrhages with slight nodular character in Sinai in New York City, where he focused on the palms of the hand and soles of the feet.”2 blood cultures and work with endocarditis. He did not refer to them as Janeway lesions. With blood cultures, physicians had a new That was done by Dr. Emanuel Libman, who tool to help recognize endocarditis earlier, and also emphasized their painless nature. the opportunity to recognize more clinical In contrast to the painless palmar Janeway symptoms associated with endocarditis at an lesions, Osler nodes are painful and in the earlier stage. pulp of the fi ngers and toes, and the two le- Libman wrote extensively on the signs sions have forever confused medical students and symptoms of endocarditis, recognizing the and clinicians alike. In a 1909 issue of the characteristic murmur, fever, splenomegaly, Quarterly Journal of Medicine, Osler described anemia, and transient petechiae (commonly the ephemeral nature of the lesions: “I have subconjunctival).9 He used these fi ndings to known them to pass away in a few hours, but diagnose the famous Viennese composer Gus- more commonly they last a day, or even lon- tav Mahler, who was conducting the New York ger,”3 and he also noted that they are painful Symphony in 1911 when he came down with to touch. a prolonged fever. Dr. Libman noted “a loud A debate still rages over the etiology driv- systolic-presystolic murmur over the precordi- ing both Janeway lesions and Osler nodes all um characteristic of chronic rheumatic mitral these years later, ranging from septic embolic disease, a history of prolonged low-grade fever, A debate to immune complex deposition to possibly a palpable spleen, characteristic petechiae on even the same etiology that just occurs at dif- the conjunctivae, and slight clubbing of the still rages over ferent locations (palms vs fi ngers).4,5 fi ngers.”10 Blood cultures confi rmed the diag- the etiology nosis and Mahler decided to cross the Atlantic ■ driving SPLINTER HEMORRHAGES and die at home in Vienna at the age of 51.11 Splinter hemorrhages are another physical Perhaps Libman is best known for his de- Janeway lesions fi nding of infectious endocarditis on the fi n- scription of noninfectious vegetations in pa- and Osler nodes gers. These small, dark, straight lines often tients with lupus erythematosus, alongside Dr. at the tips of the fi ngernails are a notoriously Benjamin Sacks.8 nonspecifi c fi nding, seen in clinical scenarios A cynic might question the importance from trauma to sepsis but made famous be- of diagnosing endocarditis earlier in the era cause their initial description was in patients where antibiotics were still decades away. But with endocarditis in the 1920s. it’s important to note that even as progress Dr. G. Blumer was the fi rst to use the term was being made in microbiology and the rec- splinter hemorrhages in 1926 after initially ognition of endocarditis was becoming more fi nding them on 2 patients with endocarditis. widespread, it was still a universally fatal con- He later evaluated 48 patients with endocar- dition. The despair caused by the diagnosis ditis and discovered the lesions only twice, so and the seriousness that the physical examina- it was quickly recognized that they were not a tion fi ndings had at the time are illustrated in very sensitive marker for endocarditis as they a journal entry of a Harvard Medical student were found in a variety of other conditions.6 named Alfred Reinhart in 1931: “No sooner Although famous, the fi ndings on hand and had I removed the left arm of my coat, than foot examination in endocarditis are rare, there was on the ventral aspect of my left wrist found in fewer than 15% of cases.7 a sight which I shall never forget until I die. CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 88 • NUMBER 6 JUNE 2021 317 Downloaded from www.ccjm.org on September 30, 2021. For personal use only. All other uses require permission. INFECTIOUS ENDOCARDITIS There greeted my eyes about fi fteen or twenty ditis was a potentially treatable disease. Cli- bright red, slightly raised, hemorrhagic spots nicians could use their diagnostic acumen to about 1 millimeter in diameter…I took one diagnose a fatal condition, implement a thera- glance at the pretty little collection of spots… peutic agent, and potentially save the patient. and calmly said, ‘I shall be dead within six months.’”12 ■ OUR CURRENT UNDERSTANDING Alfred Reinhart had a history of rheumatic OF ENDOCARDITIS fever as a child and, being a medical student, Infectious endocarditis is a cornerstone of he was painfully aware that this put him at internal medicine. Its history is a fascinating increased risk of endocarditis. He felt his fate story that coincides with the evolution of our was sealed by recognizing the rash and its rela- understanding of microbiology, and illustrates tion to endocarditis, and he was correct to the the diffi culty of making this diagnosis before month, as he died 6 months after noticing the advanced imaging. Numerous clinicians con- rash on his arm.12 tributed to our understanding of the disease by ■ ENTERING THE MODERN ERA recognizing a broad range of physical exami- nation clues, and over time, clinicians became While the early 20th century brought about more adroit at the diagnosis of endocarditis. increased recognition and understanding of Until the 1940s, endocarditis was a uni- infective endocarditis, it was not until the ear- versally fatal diagnosis. The development of ly 1940s with the implementation of penicil- penicillin quickly changed how the disease lin that there was an effective treatment. The was viewed, and the decades of work detailing antibiotic sulfonamide preceded penicillin, the diagnostic clues paid off, as patients could but its use in endocarditis was disappointing: be appropriately diagnosed and effectively eg, a review in 1943 showed only 4% of pa- treated.

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