As part of his examination, Bottone carefully opened up one of Limone’s whiteheads—tiny raised lesions filled with pus—and took a sample to examine under the microscope. He first applied special stains used to diagnose chicken pox, a viral disease. That test was normal, quickly ruling out that possibility. Using other stains, he also looked for bacteria. There were some white blood cells and a few slender rodlike bacteria. He carefully placed some of this material on a culture plate to determine what kind of bacteria, if any, were present. The culture would take a couple of days to get definitive results.
In the meantime, he told Limone to call him right away if she developed any new blemishes.
Diagnosing a patient with a rash is sometimes deceptively simple, and other times remarkably difficult. The cornerstone of any attempt at diagnosis is the patient’s history. This starts with the most basic demographic facts: age, gender, ethnicity, occupation, recreational habits, and hobbies. The next phase is for the doctor to understand the course of events. Did the rash begin on one part of the skin and then spread to another, or did it begin all over the body at the same time? Does the patient have other associated symptoms? A fever or diarrhea, a swollen joint or a headache? Is the patient taking any new medications, whether prescribed by a doctor, over-the-counter, or herbal? Is there a pet in the house? Are there any allergies, either environmental or to medications? Does anyone else in the family have a similar eruption? What about coworkers?
There are countless potential questions, and as in any detective investigation, the answer to one question often suggests several new ones. If there is a pet in the house, what kind is it, and is it healthy? If other individuals in the same household are sick, did their symptoms begin at the same time or before or after? Was there any common exposure? If there is evolution of the rash, did it spread over hours, days, or weeks?
And as in any investigation, at least at the beginning, it may not be clear which line of inquiry will yield dividends and which will end in blind alleys. So the wise clinician starts out with as few preconceived notions as possible. At the beginning, one does not usually know which answers will, in the end, be the ones that lead to the correct diagnosis.
Although the history is most important, the physical examination is also important, especially in diagnosing patients with rash. Dermatologists describe different kinds of rashes. Is it flat or raised? If raised, is there any fluid in the bumps? And if there is fluid, is it clear fluid or pus? Doctors refer to these characteristics as the morphology of a rash, and while important, morphological distinctions are limited, since the skin has only so many ways it can manifest various disease states.
A flat spot is called a macule; a raised spot is called a papule. When a papule is filled with pus, it’s called a pustule, and if it’s filled with clear fluid it is a vesicle. The morphology of a rash helps, to some extent, limit the possible causes. The rash of Lyme disease, for example, is usually a very large macule. Chicken pox is generally vesicular.
Of course the distribution of a rash is also a very important clue to a diagnosis. Is the entire body covered with the rash? Are there spots separated by normal skin, or does one flow into the others to form a large confluent area of rash? The evolution of a rash can also be valuable evidence. In a patient with blisters, are all the blisters at the same stage, or have some scabbed over while new ones are still forming in other areas of the skin?
These are some of the cases where diagnosing a rash can be deceptively simple; it is a matter of pattern recognition. The doctor will take one look and make a pronouncement with authority. A rash on one wrist may result from contact dermatitis, a reaction to something in a watchband. An eruption localized along a well-defined strip of skin (called a dermatome, an area associated with a given cutaneous nerve) is likely due to shingles, which is caused by a recrudescence of the chicken-pox virus in a particular spinal nerve.
A few days later, Limone did return, with a new pimple on her upper right arm. “I did two things,” recalls Bottone. “I asked her to see an infectious diseases specialist. He thought it was possible that the rash was something she may have contracted from an insect bite but was not impressed by the lesion. Then I referred her to a dermatologist, Dr. Marsha Gordon.”
Dr. Gordon had seen Limone a few times in the past for minor problems, including her recent case of chicken pox. After taking a look, she brought in a second dermatologist to examine the patient. “They asked me all the usual questions about whether I had used any new soaps, new detergents, that sort of thing,” says Limone. The doctors told her that they thought she had some sort of viral infection of the skin. This usually means that a person has a virus in the body that is showing itself in the form of skin lesions. The common childhood diseases—measles, German measles, and chicken pox—are typical examples.
Dr. Gordon’s handwritten office note dated June 25, 1992, reads, “Patient developed bilateral axillary lymphadenopathy 5 days ago and 4 days ago, began developing evanescent pustules—few scattered . . . presently only one pustule on right arm. Several scattered red papules (status post pustules). The oral mucosa is clear. There is increased axillary lymph nodes (no groin nodes).”
But the doctors needed to do more tests before they could provide a definitive diagnosis. It was at this point, Limone remembers, that she began to grow more concerned. She never imagined that her condition was anything out of the ordinary. “Physically, I didn’t feel that sick,” she says. “But I was really worried that no one could tell me what was causing my symptoms.”
Gordon admits she was a bit puzzled. Based on Limone’s medical history and the fact that her lesions did not fit the patterns of various other infections, the dermatologist was able to rule out the most common causes of such symptoms: shingles, herpes simplex (the virus that causes cold sores, which can sometimes spread throughout the body), and contact dermatitis—a rash or other allergic reaction that occurs when the skin touches an irritant. Because the morphology of the lesions was pustular, the possibility of a sexually transmitted disease—disseminated gonorrhea—was also raised, but for all sorts of clinical and epidemiological reasons, this diagnosis was immediately discarded.
The dermatologist thought that a nonspecific viral cause was most likely, but was waiting anxiously to see the results of the culture that Bottone had taken, because there was one other possibility that the doctors were considering.
So Gordon was relieved when the lab report showed a crucial piece of information that would help narrow the search. The tests that Bottone had done on samples from Limone’s lesions turned out to be positive for a rather unusual bacterium called Pseudomonas aeruginosa, which we will call PA. At least now the doctors knew what was causing Limone’s symptoms. But having this particular label offered little solace.
The pseudomonas is a large group of bacteria; there are hundreds of individual strains. They were first described in 1894. Most are completely harmless and do not cause disease in humans. Pseudomonas aeruginosa is an extremely hardy bacterium that can grow under almost any conditions, as long as there’s moisture. The bug is commonly found in soil, water, and on the surface of plants and animals.
Its nutritional requirements are extremely basic, which allows it to grow just about anywhere. The bug produces two types of soluble pigments: the fluorescent pigment pyoverdin and the blue pigment pyocyanin. The blue pigment functions in iron metabolism in the bacterium. It is also responsible for the so-called “blue pus” that is a characteristic of PA infections.
The PA bug especially loves swimming pools, and because it grows over a wide temperature range, it will also lurk in whirlpools and hot tubs that have not been properly disinfected with chlorine. Healthy people don’t normally get PA infections; it’s more common in those whose immune symptoms have been weakened by chemotherapy or a serious illness or other infection. PA is called an “opportunistic” bacterium. This means that, although it does not normally infect humans, when given the chance it will strike and often with a
vengeance.
It causes severe, often fatal infections in patients whose normal host defense mechanisms are compromised. Patients with burns, cancer, AIDS, diabetes, and cystic fibrosis are particularly vulnerable. Once inside the body, the bacteria can cause severe infections of the bloodstream, heart, lungs, urinary tract, skin, eye, external ear canal, bones, and joints.
Even though it is rare, PA can occasionally cause infections in healthy individuals. Given its proclivity for moist environments, it can often be cultured out of tennis shoes, and if a person steps on a nail while wearing a shoe, the PA is often inoculated into the foot and can cause a serious bone or joint infection. Another condition sometimes reported in nonimmunocompromised people is a skin infection called folliculitis (an infection of the hair follicles).
Folliculitis from PA was already a well-known entity in 1992. In the mid-1970s, articles began to surface that described people developing PA skin infections after bathing in whirlpool tubs. One of the first was a paper published in the Journal of the American Medical Association that documented thirty-two individuals who developed generalized pustular rash after using a particular whirlpool in Minnesota in March 1975. The attack rate was over 50 percent, since sixty-one people had been exposed. The rash appeared in as few as eight hours to as late as two days after exposure and resolved within seven days. None of the thirty-seven motel guests who did not use the pool developed the rash. The same strain of the bacterium PA was isolated from the skin lesions of some of the patients as well as from the water. The authors concluded: “Circumstantial evidence implicated the whirlpool as the most probable source of infection. Deficiencies in disinfecting equipment and technique were identified and corrected.”
Numerous other reports followed. The common denominator seemed to be heavy usage of a hot tub or exposure toward the end of a day (suggesting that the number of humans in the tub, or “bather density,” was an important factor) and time spent in the tub. The degree of chlorination was also an issue, as was the temperature. The incubation period in all these early studies was usually no longer than forty-eight hours, and all cases resolved. There were some reports of people becoming infected in home hot tubs, and others documented infections that were not limited to the skin. Patients developed pneumonia, urinary tract infections, and keratitis (infection of the cornea) after hot tub exposures.
In 1980, doctors in Tennessee reported a slightly larger outbreak, this one related to exposure to an indoor swimming pool at a health club. The first hint of a problem was in November, when a local physician reported the occurrence of unusual skin lesions in three patients whose only common link was membership in a health club. A culture done on one of the patients grew out PA. The CDC was called in to investigate, and the inquiry uncovered a total of thirty-seven members who developed a pustular rash that had started hours to days after use of the swimming pool. Another ten patrons had symptoms of an external ear infection also thought to be part of the outbreak, but without any skin involvement.
A month before the outbreak, the club had installed a new indoor heated swimming pool with an automatic filter and chlorinator. On Wednesday, November 5, the managers noticed that the pool water was turbid. When they checked the chlorinator, they discovered that it was broken. The pH of the water was higher than it should have been, and they could not detect any free chlorine. But while they made the necessary repairs, they kept the pool open to the members.
The investigators found that, as is typical for PA, only hair-bearing skin was involved (as would be expected from a folliculitis). The palms of the hands, soles of the feet, and mucous membranes were never involved. There was a predilection for the buttocks, axilla, and trunk, but not typically the arms and legs. Many patients had low-grade fever or a feeling of malaise. All of the patients had normal immune systems, and they all got better without any serious consequences.
The authors of the Tennessee study also focused on forestalling further outbreaks, concluding: “Prevention of pseudomonas folliculitis should be possible by maintenance of pool water at a pH of 7.2–7.8, and free available chlorine levels at 0.5 mg/liter. Swimming pools usually are maintained within these limits, which may explain why outbreaks associated with them are rare. It is more difficult to maintain adequate pH and chlorine levels in heated whirlpools and baths because their heavier load of bathers per volume of water creates a greater demand for chlorine, and their higher temperatures and agitation cause an increase in loss of chlorine into the air.”
Three years later, in 1983, the CDC reported an even larger epidemic, this one associated with use of a waterslide in Utah. The first patients developed symptoms on the evening of April 30. On May 3, the Salt Lake City-County Health Department notified state authorities that people were developing skin rashes and earaches after using a long curved slide that empties into a pool. By May 7, just four days later, 265 cases had been identified. The investigators sent out questionnaires to more than 200 people from two church groups that had visited the facility on April 30. Of people who went on the waterslide, 76 percent got sick, but none of the unexposed visitors developed symptoms.
Of those who did fall ill, over 90 percent had the characteristic skin lesions. Nearly half had headaches and a quarter had fever. In a particularly unusual case, one patient had a temperature of 104 degrees and needed to be hospitalized.
For patients who already suffer from a serious illness, exposure to PA can have quite different outcomes, as is seen from a small outbreak in a major Iowa hospital. Over a fourteen-month period, seven patients, all of whom had forms of leukemia, were diagnosed with PA infection, which came from the drain of a whirlpool bath in the hospital’s oncology unit. Four of the seven died.
Armed with the positive PA culture, and knowing the organism’s predilection for water, Bottone focused his next round of questions for Limone on various aquatic exposures. If the infection had started during the trip to California, the incubation period would be exceptionally long. But this is where Bottone’s started.
“When the culture turned positive for PA, Dr. Bottone asked me all sorts of other questions,” Limone recalls. “Because of my California trip, he had me retracing my steps, verifying that I hadn’t gone into a sauna or a hot tub.
“Then he asked me to think about my daily routine; he really got into the nitty-gritty,” says Limone. “It was a bit embarrassing because we had a strictly professional relationship, so it was a little out of place. But he was now in the capacity of the clinician and I tried to view him that way. He had lots of questions.
“Did my husband use the same washcloth as I did? The same bar of soap? How many showers did I take? When did I shave? What lotions and creams did I use? I had to bring all my toiletries to the lab. He took cultures of my soap, baby lotion, moisturizing cream, and shaving cream, thinking that one of them might be contaminated with the bacteria.”
But they weren’t.
Still, Bottone was convinced that Limone must have come in contact with something harboring PA. “Knowing that the normal habitat of this organism is moisture, I persisted,” Bottone recalls. “I asked her how she took showers. When I asked about the washcloth, she said, ‘No, I use a loofah sponge.’ At the time, I had no idea what a loofah sponge was, so I asked to see it.”
Something clicked when Bottone saw the loofah. “Josephine brought this big sponge in,” he recalls. “It was still a little wet, and when you squeezed it, a small bit of water with a greenish tint dripped out.” Dr. Bottone was well aware of the pigments that PA forms—pyoverdin and pyocyanin. The green liquid that oozed out of the loofah was clearly consistent with those pigments. Figuring it was some kind of bacteria, he had the sponge tested. It was loaded with PA.
Although they look like something that might come out of the sea, loofah sponges (or luffa as they are sometimes called) are actually made from the gourdlike fruit of a tropical and subtropical vine called Luffa, a genus that includes six species. The ripe fruit resembles a large cucumber, which is not su
rprising because the plant belongs to the Cucurbitaceae family, which also includes cucumbers, squashes, gourds, and melons.
The vines are traditionally cultivated in India and the Middle East, where the name originates, and are also grown in other warm, dry regions. Loofah is harvested for food in many parts of Asia. All species are edible if the loofah fruits are cooked and eaten before they mature; otherwise, they are too tough to eat. Loofah sometimes appears on menus as Chinese okra.
The loofah is the only plant source of sponges, which have been used in kitchens and bathhouses for centuries. When grown to make sponges, the loofah fruit is allowed to mature and dry on the vine. The woody exterior skin is peeled away, and the seeds are shaken out for replanting. The drying process leaves behind only the network of xylem, which is the tubular transport system used to carry nutrients from one part of the plant to another. This dense web of straw-colored fibers will puff up again once the loofah is moistened.
The resulting sponge is most commonly used in place of a washcloth in the shower. Many people prefer to use the loofah as a dry exfoliating brush before bathing, which gently removes the surface layer of dead skin and leaves the skin smooth and conditioned. In the kitchen, the loofah’s coarse texture makes it great for cleaning dishes and countertops, but it is gentle enough for use on delicate items like coated cookware that could be damaged by normal abrasives. Like other sponges, loofah will collect bacteria if it is kept moist and warm, and because they are made from a living organism, loofah sponges can hold bacteria more easily than synthetic fibers.
But how, Bottone wondered, did the bacteria get there in the first place? Unfortunately, he wasn’t able to come up with any definitive answer. He did prove that the PA strain in the sponge was the same one that he had cultured from Limone’s skin lesion. It was the exact same serotype, so it was certain that the loofah had infected Limone.
The Deadly Dinner Party: and Other Medical Detective Stories Page 7
