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We’ve made a rare diagnosis. What happens next?

In our last post, a patient’s presentation with features of a rare disease gave us an opportunity to discuss how diagnoses are made. We saw that the pattern recognition that matches findings and data with the large matrix of potential diagnoses is a semi-scientific process. It turns out that people exist in nature with strange combinations of symptoms that agree with well-described diagnoses. This makes us feel more confident that our medical edifice is on solid footing.

A number of you, dear readers, were curious to know how the little girl with the very rare inflammatory disease of blood vessels (Takayasu arteritis) is doing. It will take some time to get a sense for whether or not she is responding to steroid therapy (I’ll see her back for the first time next week). An additional challenge in her case is that since she has little in the way of symptoms (besides her high blood pressure) or lab abnormalities, we will need to repeat her sophisticated MRI imaging over time to know if her treatment is working.

Although having the correct diagnosis (or diagnoses) can be a major barrier for patients with mysterious symptoms, I think that the correct diagnosis is less often the main obstacle that keeps patients from getting better. Treatment, no matter how seemingly straightforward, is where the devilish details lie. The application of Systems Science to medicine in recent years has revealed how many decision points, information transfers and potential sources of error occur between a correct diagnosis and a correctly administered treatment. Even when the patient takes the treatment in the right dose, at the right time, in the right way – does everything the doctor asks – variation and complexity send the doctor and patient back to the therapeutic drawing board. Figuring out treatments that work is an empiric process and this trial and error is the backbone of what people like to call the “art of medicine”. We can talk about what “art” is (preferably over some good wine), but I’ll say that medicine doesn’t strike me as much of an art. I think that it is more of a craft: a particular type of problem solving that occurs at the intersection of what is known, what is needed and what is possible. The social situation of patients has an enormous impact on both the needs and the possibilities. Two patients that I met on one day last week provided a dramatic reminder.

Monday Morning’s Case: a 5 year old African American boy with weakness and rash

Barry was my second patient of the day in our Monday morning clinic. His grandmother and mother told me that Barry had been a healthy kid until late May when they noticed that Barry began to limp when he was running and going up stairs. He also began to complain that his shins hurt when he would walk for longer distances. After several weeks, they noticed that Barry had a dry looking red rash over his knuckles, knees, and elbows. They took Barry to see his pediatrician in late June. She saw that he clearly had weakness particularly in his upper arms and thighs. She took a close look at Barry’s hands and felt pretty confident that she had seen that raised, red rash over the knuckles before. She ordered laboratory tests including enzymes that are released when muscle cells are damaged by inflammation. The blood levels of several of the enzymes were elevated. Although the disease that was causing Barry’s weakness and rash is also very rare (between one-in-a-million and five-in-a-million kids), his pediatrician had done a rotation in our pediatric rheumatology clinic during her residency and had seen patients with it before.

She promptly referred Barry to our group and the visit was for a planned admission for Barry to have two definitive diagnostic tests (MRI of his hips and thighs to look for muscle inflammation, muscle biopsy to confirm the diagnosis) and to have intravenous infusions of high-dose steroids to begin his treatment.

Barry’s mother and grandmother were relaxed and poised. They sat watching impassively even while Barry could not do tasks that would be simple for most kids his age, like climb up on to the exam table or keep his head lifted up off of the table while lying on his back. Although not medically sophisticated, Barry’s mother was prepared for our conversation. She had read patient information handouts about Juvenile Dermatomyositis and its treatment. She asked good questions and wanted to know more about what to expect for Barry’s initial treatment. Based on a composite view of the small signifiers that we use to size up each other’s socioeconomics (clothes, phones, purses, speech, etc.), I would say that the family seemed to be middle-middle class. Barry’s mother probably had a career and some post high school education. I did not ask about Barry’s father. The hospitalization lasted for three days and went smoothly. The MRI and muscle biopsy confirmed the diagnosis of Juvenile Dermatomyositis (JDM) and Barry did well with the steroid infusions.

Monday Afternoon’s Case: a 4 year old African American boy with weakness and skin lesions

I made my way over to the big house (our large children’s hospital) with my senior attending (boss) to see our admitted patients. We saw a school-aged girl with episodic hip pain who was waiting to have an MRI. A new patient with lupus and renal disease had been admitted from our clinic to be treated with high-dose intravenous steroids. By about 4:30 we were wrapping things up, gossiping about departmental politics, and getting ready to head home. I got a page from one of our pediatric hospitalists, the text message said “new-onset dermatomyositis”. We walked over to the nurses’ station and found our colleague. The page was still fresh. We could see the just-sent message up on the monitor in front of him.

He told us the story of a 4yo African American boy who had been transferred from the emergency room of a nearby regional hospital the night before.  Ricky, we’ll say, spent his first two months in the neonatal intensive care unit of the same regional hospital. His mother was addicted to heroin and Ricky was born with dependence to the drug, a condition that is sometimes called “neonatal abstinence syndrome”. His development and growth were delayed. We were told that he eventually caught up in his height and weight and his movement skills. About 6 months ago, Ricky’s grandmother, his primary caregiver, noticed that he started to walk slowly and that he would tire out more easily. What happened in between was unclear, but things progressed to the point that Ricky had to be carried and lifted to go up stairs and to make it into his car seat. We were told that he was unable to walk and was getting around his house by scooting on his bottom. He was brought to the emergency room because of skin ulcers on his bottom and in his arm pits. The outer layers of the skin of his buttocks had literally been rug-burned away leaving the raw, red deeper dermal layer exposed. His skin was fissured and torn where he had repeatedly been lifted with hands placed under his armpits. He had low-grade fevers, probably from infection of the skin wounds, and the hospitalist had started treatment with an intravenous antibiotic overnight.

Ricky had seen specialists at the regional hospital over the prior two months. Records with sufficient information to fairly well establish the diagnosis of JDM came over on the fax machine. Notes from the doctors there indicated that they would begin to start treatment for dermatomyositis when the muscle biopsy results had been reviewed by an expert pathologist.  We were not quite convinced by the quality of the records to be sure that Ricky was also a one-in-a-million child with JDM. It was unclear whether the delay in initiating the treatment was due to challenges faced by Ricky’s family or hesitation and uncertainty on the part of his doctors (or, most likely, both).

Ricky lay perfectly still under the starchy white sheet, looking up at the ceiling. His long hair was braided into ponytails, thin ropes draped outward on the pillow. The sweetness and sadness of his expression made him unbearably cute. His grandmother stood at the side of the bed. It was hard not to flinch while looking at her and shaking her mangled hand. Her face, neck and arms were disfigured by surgical scars connecting a patchwork of rectangular segments of skin. There were four fingers on each gnarled hand; her thumbs looked like they might have been repurposed index fingers. We did not have the heart to ask what had happened to her, particularly at that first meeting, but it seems that she had needed extensive skin grafting because of a terrible burn or accident.

Ricky’s grandmom told us about a trip the family had taken in November and the weakness that began in February. Detail was scant and we quickly found ourselves in the present, with Ricky unable to walk and the skin lesions caused by the floor and the car seat prompting the emergency room visit. She was unaware of the provisional diagnosis made by the doctors at the regional hospital. She was concerned about Ricky but had not discussed how the weakness might be treated. We mustered our most soothing voices to ask Ricky how he was feeling. When he quietly told us that he was OK, his grandmother reminded him to address my boss as “Mame”. Later in the week we were back at Ricky’s bedside while a wound care nurse changed his dressings. Although he had been given a dose of morphine, tears welled up in his eyes the moment the nurse began to loosen the tape. It was a very difficult thing to watch.

All disease is social (All politics is local)

JDM is a rare inflammatory myopathy that affects skin, muscle, and at times other internal organs. Like Takayasu arteritis, vasculitis (inflammation of blood vessels) appears to be a component of the condition although small vessels are affected. The underlying immunologic and cellular cause of the disease is still an area of significant mystery. Last year, I tried to make a divot in this small corner of the unknown medical universe by determining the types of genes that are expressed in the blood cells of patients with active and well-treated disease. It appears that many of the genes that signal the immune system’s response to an active viral infection are turned on in the blood of patients with acute disease. We see a similar pattern in lupus. It seems as though some trigger (perhaps viral infection?) sets off an exaggerated and prolonged inflammatory response that causes tissue damage in these children with a very specific, and unknown, genetic predisposition.

It took several days for Ricky’s muscle biopsy slides to make it to our neuromuscular pathologist. The pattern of inflammation was consistent with JDM, clinching the diagnosis. There were some calcium deposits present in the muscle, suggesting that the inflammatory process had been going on for at least months, possibly years. With continued intravenous antibiotics, Ricky’s fever improved and with the careful attention of the wound nurse, his skin is healing. Although he is now receiving intermediate daily doses of steroids, we still have not felt ready to pull the trigger on the high-dose intravenous steroids he needs until his skin wounds are better healed.

Barry and Ricky are two little boys of almost the same age and ethnicity who were diagnosed with the same rare disease during the same week. The social circumstances that influenced the path towards a diagnosis and the initiation of treatment differ dramatically. As with many of our inflammatory and autoimmune diseases, we now have good data that early aggressive treatment employed to dampen down and stop the inflammatory cascade before tissue damage accumulates leads to better outcomes in JDM. Barry’s diagnosis was made about as quickly as could be hoped and his treatment went forward without delay. We are only beginning to deal with Ricky’s acute illness. Although he has the same disease as Barry, Ricky’s unique version of JDM may well be more severe due to delayed diagnosis and treatment. Most worrisome, the biggest obstacles standing in the way of his recovery may still lie ahead.

I can think of many moments back on Longwood Ave. during residency when a seasoned clinician would interrupt a subordinate’s presentation about a patient with a newly diagnosed disease to ask, “OK, what is the family like?”  I was annoyed by this. It seemed presumptuous to skip past the medical details to dig into a description of the family’s circumstances, what we usually call the “social history”. I wondered if this was motivated by voyeurism. The master clinicians had diagnosed patients with even rare diseases so many times before, it seemed that they were mainly interested in the juicy details of whether or not there was a “good mom” and if the father was “involved”. Now I can see that with their years of experience, perhaps they had come to appreciate that the particular challenges of working with a family to optimize a child’s treatment really was the most important thing that they could ask about, even on Day One. Nowhere has the importance of the social history been written about more eloquently then in a commentary by Chen Kenyon, friend of Left on Longwood, published four years ago today in Pediatrics.

JDM is a very treatable condition. It is one of the pediatric rheumatic conditions that we think can be truly cured (superstitious or not, we are a little more comfortable calling this “stable remission off medications”). We will work with Ricky and Barry’s families towards this hopeful outcome. The paths traveled to get there from here may be very different.