On Thursday we challenged Well readers to take on a case of a 29-year-old woman and her boyfriend who developed matching rashes: hers on her arm, his on his abdomen. Many of you recognized how important it was to factor in their recent trip to Brazil in making this diagnosis. Indeed, more than three-quarters of you suggested some type of tropical disease, and nearly half of you nailed it. (Does that mean the case was too easy?)
The correct diagnosis is…
Cutaneous leishmaniasis
The first correct answer, posted just five minutes after the case went up, came from George Bonadurer, a second year medical student at Mayo Medical School in Rochester, Minn. Like many of you, he said that seeing the picture of the lesions plus knowing that the couple had traveled to Brazil led to a diagnosis of leishmaniasis.
The Diagnosis
Leishmaniasis has a long history. First century pre-Incan pottery from Ecuador and Peru carried images of the terrible skin lesions and facial deformities that are typical of the cutaneous form of the disease. And accounts from Spanish conquistadors spoke of seeing ulcers on people living in the jungles or mountains that looked like the lesions of leprosy. They called it white leprosy or Andean sickness.
At the start of the 20th century it was renamed after Sir William Leishman, a British Army doctor serving in India, who first identified the parasite causing the visceral form of the disease. Dr. Leishman himself called the illness “dum dum fever” after the village where the soldier he cared for had been posted.
The parasite causing leishmaniasis is transmitted by the sand fly, a tiny bloodsucking insect. The disease cannot be transmitted from person to person. The sand fly and the single-celled organism it carries are common in much of South America and Africa and affect millions of people worldwide every year. Although there have been home-grown cases of the disease in Texas and Oklahoma, the vast majority of those diagnosed with leishmaniasis in the United States contract it outside of the country and bring it home.
Various Forms of Disease
The most common form of leishmaniasis manifests as a single sore at the site of the bite weeks, or sometimes months, after the bite. The lesion, although dramatic in appearance, is often painless. It will usually heal on its own but, without treatment, can linger for months or even years, allowing the lesion to grow into large, sometimes disfiguring sores that leave terrible scars when, and if, they heal.
Some species of the parasite can cause a disease that spreads to the nose and mouth. Occasionally it can spread to the viscera — this form is sometimes called “kala azar” — causing even more devastating disease and sometimes death. Prompt diagnosis and treatment can limit the size of the lesion and the scar and prevent the spread to more delicate tissues.
Travelers to endemic regions are encouraged to cover up as much as possible and to use high potency insect repellents on exposed areas. If significant exposure is likely, clothing can be treated with an even stronger insecticide, permetherin. Since sand flies are most active at night, sleeping with mosquito netting is recommended if not sleeping in well screened or air conditioned rooms.
How the Diagnosis Was Made
When Dr. David Antonetti saw the patient and the sore on her arm, he took samples of the pus-like discharge to see if anything would grow. When nothing did, he called the patient and told her to stop taking the antibiotics he had started her on.
Dr. Antonetti was not surprised by the culture results. He did not think this was a typical skin infection. Indeed, when he found out that she had recently visited Brazil, he immediately thought of leishmaniasis.
He had never seen a case of it himself, but the dramatic images of leishmaniasis lesions he had seen in medical school made a strong impression on him. Even as he sent the samples to the lab for culture, Dr. Antonetti reached out to Dr. Matthew Grant, an infectious disease doctor he had worked with before, telling him “I’m sending a patient to see you who might have leishmaniasis.”
Dr. Grant got a call like this two or three times a year. He would then call the Centers for Disease Control and Prevention to obtain the culture medium needed to send tissue samples for genetic identification of the organism. He would stick the test tubes with the proper medium they sent in his home refrigerator, ready to be used if the lesion seemed likely to be leishmaniasis and a biopsy or other sample was obtained. Most of the time he hadn’t needed it. Patients usually had something a little more common. Still, he wanted to be prepared.
A Second Opinion
Dr. Grant saw the patient the following week. The sore certainly looked like leishmaniasis. Still, there were other possibilities he didn’t want to overlook – other rare infections that can cause this type of open wound on the skin. He tested her for each of these oddities and arranged for a skin biopsy to be sent to the C.D.C.
The full results of these studies took a couple of weeks, but when the results came back Dr. Grant was worried. The patient had leishmaniasis, caused by one of the most aggressive species of the Leishmania protozoa. Patients with this form of the disease are at the highest risk that their infection will spread and must be treated with strong medications.
Same Medicine, Different Results
The patient’s boyfriend was also shown to have been infected with the same species of leishmania. Both were given amphotericin B, a powerful antimicrobial known by many doctors as ampho-terrible because it often makes patients feel terribly sick and can damage the kidneys.
Both came through treatment without difficulty. The boyfriend’s rash healed completely. The patient was not so lucky. A couple of weeks after treatment, tiny oozing bumps appeared around the original site. Recently new bumps appeared – this time on her face.
In early November she was given a second medication. It did nothing. What to do next is not clear. This is a rare disease in the United States. Many of the medicines used to treat this disease aren’t even available in this country.
The patient is understandably anxious. This can be a devastating disease. And it is an infection that can be passed on in utero, should she decide to have children. “I can deal with the scars, but I’m worried about what’s beyond that,” she said.
When Treatment Doesn’t Work
Often we think that getting a diagnosis will lead to cure, and certainly getting the right diagnosis is an essential first step. But treatment is not always successful. Amphotericin B is effective about 85 percent of the time. But what happens when it doesn’t work?
Her doctor is trying to sort that out. There is a new medication recently approved by the Food and Drug Administration to treat leishmaniasis called miltefosine, but it is not yet available in the United States. Dr. Grant and the patient are trying to figure out how to obtain it.
Leishmaniasis is a tropical disease and, like many of these diseases, common in regions with limited resources. Because of this, Dr. Grant says, the disease has been understudied and there is little agreement about the most effective treatment regimen. The Infectious Diseases Society of America is planning to release guidelines on the treatment of the disease in the fall of 2015. With any luck — and this new drug — this patient hopes to be better well before those guidelines come out.
Some readers were very critical of the doctor for not seeking medical care sooner — and for potentially putting her patients at risk. However, at the time she got sick, she was a resident, dealing with all the pressures residents face, including the knowledge that if she called in sick one of her colleagues would have to cover for her. One of the problems in medicine is that these young doctors feel enormous pressure to show up to work no matter what — and while it would be easy to blame this young woman, the larger issue is one of medical culture, something that will be harder to change.