Cognitive bias. Type 1 thinking. Heuristics. Such terms often feature in modern discussions of diagnostic errors. But for one physician-father in Colorado, simple words say it all.
“If only I had made the connection between Costa Rica and cutaneous ulcers…” Andy Mohler, MD, sighed while speaking about the parasite that recently wreaked havoc on his daughter’s knee.
The case itself is instructive, but for a tropical medicine specialist, it also raises questions. Are American doctors up to speed on parasites? How many infections are missed altogether — and how many diagnoses are dangerously delayed?
Mohler is a respected family practitioner who recalls a lecture in medical school that mentioned his daughter’s now nemesis. More recently, he also read a best-selling book — The Lost Kingdom of the Monkey God — that contains vivid accounts of the same blight that struck Maddie. So, what’s wrong with this picture?
But first, the saga.
The Hole in Maddie’s Knee
In hindsight, a long incubation was partly to blame. After vacationing in Costa Rica in December 2021, 5 weeks passed before Maddie Mohler found a flesh-colored, 5 mm bump on her knee. By then, the high school senior who loved physics, math, varsity track, and her part-time job at Safeway was focused on other things. Plus, nothing medically memorable — not a day of diarrhea, not a single itchy bite — had marred the Mohlers’ trip.
This meant that no one, including two medical parents and the patient herself, connected the dots.
Then more papules erupted on Maddie’s knee, followed by a grape-sized inguinal lymph node. By March, the papules had coalesced, blistered, and opened, creating an ulcer that wouldn’t heal. Finally, after the 100-pound runner finished a second round of cefalexin (Keflex) for (possible) cellulitis, and Vaseline and hydrocortisone cream still weren’t taming her ulcer’s maddening itch, Maddie saw a dermatologist. This doctor didn’t ask many questions but proffered a biopsy. When Maddie demurred, granuloma annulare (GA) was the new working diagnosis.
“Hmm…” thought Maddie after scanning online photos. Wasn’t her ulcer deeper than those of other GA patients? Nonetheless, she now applied clobetasol, a highly potent topical steroid. The results were not good. Not only did her ulcer continue to cavitate, at times it was excruciating.
“On a scale of one to 10, the pain was almost always six or seven, but if I bumped myself, or even if my pants were tight, it could spike to 15 within seconds,” Maddie recalls. Thus, she wore shorts and kept her lesion bandaged. Finally, with the hole now a disturbing well with a new magenta satellite, Maddie returned to the dermatologist.
The true diagnosis soon followed. What Maddie’s biopsies showed were intracellular nests of Leishmania.
Spoiler alert: this story will barely scratch the surface of a single-celled parasite inoculated by sand flies that affects 700,000 to a million people in five continents every year and causes three forms of disease: visceral, cutaneous, and mucocutaneous. Let’s focus on the third. Central and South America are the traditional home of mucocutaneous leishmaniasis (MCL), a sometimes-gruesome condition that can surface months to years after certain Leishmania strains migrate from a patient’s skin to their naso-oropharynx. Furthermore, Leishmania guyanensis, the species that infected Maddie, can trigger MCL.
Thankfully, Maddie’s ENT exam showed no intra-oral or -nasal spread. She then met with an infectious diseases doctor who considered various therapeutic options including two older, injectable treatments or miltefosine (Impavido), a newer, pricey pill. The doctor then recommended the latter as the best initial choice both to heal Maddie’s ulcer and prevent future problems.
Six weeks after his initial email (when he first wrote, Maddie’s dad had not yet received the final report of Maddie’s Leishmania species), his follow-up message was short but reassuring.
“The PCR came back as Leishmania guyanensis,” Mohler wrote. “Our local ID doc prescribed miltefosine three times daily for 28 days. She had some nausea and vomiting throughout the course, as expected, but yesterday was her last day of treatment and the ulcer is dramatically better. Fingers crossed, but it looks like it is almost completely healed.”
Morals of the Story
Maddie’s difficult road to diagnosis and care will not surprise anyone who’s treated leishmaniasis in a returning American traveler. While the number of U.S. doctors experienced in managing leishmaniasis remains relatively small, the number of people at risk for infection continues to grow with rising rates of international travel and migration in addition to cases in soldiers, especially those deployed to Iraq and Afghanistan.
There are also those in whom Leishmania parasites lie in wait, then befuddle and confound. For example, I once saw a woman born in Brazil whose MCL was originally labeled “chronic sinusitis,” then erroneously diagnosed as Wegener’s granulomatosis and treated with heavy immunosuppressants for 7 long years. As with Maddie, this faulty treatment only made things worse. It also brought severe emotional stress.
Co-infection with HIV also weakens host defense to visceral leishmaniasis, increasing chances up to 2,000-fold that a latent infection will re-activate. In this case, unless they receive effective treatment, patients die.
But rather than dwelling on war stories, what are some solutions? How about a couple of hours of “basic training” around important global parasites, including Leishmania, as a regular CME requirement for front-line physicians in family, internal, and emergency medicine, dermatology and pediatrics? Such education need not dwell on every detail of diagnosis and treatment (in many cases, such matters are handled by specialists in infectious disease), but could cover prompt detection based on key clinical features and histories of overseas residence and travel.
In closing, I can’t help but remember Mohler’s rueful statement: “If only I had made the connection between Costa Rica and cutaneous ulcers…”
What’s the best online reference that could have helped him? CDC’s “Health Information for International Travel,” otherwise known as the Yellow Book, is one great resource. When I recently went online and accessed the latest edition, typed in “Costa Rica,” and navigated to “Non-Vaccine Preventable Diseases,” the four vector-borne blights that appeared were Chagas disease (American trypanosomiasis), dengue, Zika, and (of course) leishmaniasis.
Claire Panosian Dunavan, MD, is a professor of infectious diseases at the David Geffen School of Medicine at UCLA and a past president of the American Society of Tropical Medicine and Hygiene.