On Thursday we asked Well readers to take on the difficult case of a 64-year-old contractor who had had a blistering rash on his hands off and on for over 20 years. The man saw the rash as simply annoying, but the diagnosis suggested an important underlying medical problem. Your challenge was to identify both the cause of the rash as well as the underlying diagnosis.
The rash was from: Porphyria cutanea tarda
Which was in turn caused by: Hereditary hemochromatosis
I thought this was a really tough case, but many of you were able to recognize the rash, and some of you figured out the cause as well. Amazing!
The first reader to send us the correct answer was Nick Zampariello, a second-year medical student at Boston University. He tells me he just finished his dermatology block and so was eager to take on a case with a difficult rash. He figured (correctly) that the rash was limited to the patient’s hands because of sun exposure, and then recognized the rash of this type of porphyria. The post-summer tan suggested the underlying cause of hemochromatosis.
About the Diagnosis
The porphyrias are a group of diseases caused by a problem in the breakdown of hemoglobin, the oxygen-carrying part of red blood cells. The name comes from the Latin word for purple (porphyros), because with some forms of this disease, the unbroken-down parts of hemoglobin are eliminated from the body in the urine, and those chemicals can make the urine turn purple when exposed to sunlight.
Unlike other forms of this disorder, porphyria cutanea tarda, or P.C.T., usually arises as a result of an underlying disease. It is inherited in only about 20 percent of cases; and in those who inherit the gene, the patient doesn’t develop any symptoms until another disease causes additional injury.
The rest of the name highlights the disease’s most characteristic qualities: It affects the skin (cutanea) and it appears late in life (tarda). In P.C.T., the particular components of hemoglobin that are not fully broken down migrate to the skin, where they cause a blistering sore when exposed to sunlight.
P.C.T. usually arises as a result of injury to the liver. The most common cause of injury is infection with the hepatitis C virus. However most people with hepatitis C do not develop P.C.T. Nor is it understood why P.C.T. develops in some diseases associated with liver injury – hepatitis C, alcohol abuse, hemochromatosis – but not in others that can be just as damaging to the liver, such as other types of hepatitis.
Hemochromatosis, the cause of P.C.T. in this patient, is an inherited disease in which patients absorb too much iron and are unable to get rid of it. Although iron is essential for many body functions, too much of a good thing – as with most things — is bad.
In patients with untreated hemochromatosis, the excess iron infiltrates tissues – liver, pancreas, skin – interfering with their normal function and causing disease. Cirrhosis of the liver, heart failure or diabetes may result. Indeed, hemochromatosis is sometimes known as bronze diabetes because most who have it not only develop diabetes, but their skin darkens from the deposition of iron just below the surface.
Iron deposits injure the liver and trigger the P.C.T. well before the development of cirrhosis. Treatment of hemochromatosis reduces the iron burden and the P.C.T. resolves.
How the Diagnosis Was Made
Dr. Janelle Duah, the doctor in training who saw the patient at the Veterans Affairs Hospital in West Haven, Conn., was finishing up her first visit with the Vietnam War veteran when he brought up one more problem he wanted to talk with her about. He had these blisters on his hands, and they were driving him crazy. He’d been getting them off and on for over 20 years, but recently, in the last year or so, they had gotten much worse. Now it seemed like he had a few blisters on each hand all the time.
Here’s what his hands looked like a few weeks after Dr. Duah first saw them.
Dr. Duah wasn’t sure what this was, she told the patient. It seemed like it had been around too long to be a contact dermatitis, an allergic reaction to something he had come in contact with. There were some autoimmune diseases that could cause blisters, but she wasn’t sure if they could be limited just to the hands. She was curious to see what the supervising doctor, Dr. Kathleen White, would have to say. She knew that Dr. White loved derm.
A Case for the Dermatologists
It did look a bit like a contact dermatitis, Dr. White agreed, when she entered the room. But, asked Dr. Duah, would it last this long? Should we send him to the dermatologists?
Dr. White took a good long look at the man. He was of regular height, and muscular. Pretty healthy looking. His face was red. That’s a July beach day red, Dr. White thought to herself. O.K., let’s send him to see the dermatologist, Dr. White agreed. But then let’s talk later and see if we can figure it out for ourselves.
She knew the intern was running late and had other patients waiting. She wanted to encourage the intern’s curiosity, but also wanted her to learn the value of being on time for patients.
Sunburn in Autumn?
Dr. Duah went on to her next patient, and Dr. White went back to her computer. It was October, and yet the man had what looked like a sunburn. Could he have some kind of sensitivity to sunlight? Could that cause the blisters?
She turned to UpToDate, one of the online medical encyclopedias available to her. A quick search took her to an entry on how to approach a patient with a rash like this.
She quickly scrolled through the lengthy entry to look at the pictures. Not eczema. Contact with certain plants could trigger a blistering rash in the sunlight, but his rash seemed too persistent to have that kind of trigger. The kind of autoimmune diseases that Dr. Duah had been thinking of could cause these kinds of blisters, but they were usually found in the mouth as well as on the skin.
Spotting the Rash
Then she saw it. A picture of a scabby scarring rash, just like this patient’s. On the hands. And triggered by sun exposure. She had never even heard of this disorder, but she was pretty sure it was what this man had: porphyria cutanea tarda.
She quickly read up on the disorder. Convinced that this was the correct diagnosis, Dr. White was eager to share her discovery with the intern right away. She went to the room where Dr. Duah was seeing her next patient and, apologizing for the interruption, handed the resident a note.
I think I figured out your patient’s rash, the note read. Then it went on: Look up P.C.T.
Dr. Duah quickly finished up with her patient and hurried out to find Dr. White. The doctor showed the images to the intern. That was it, Dr. Duah agreed. That was exactly what her patient’s hands looked like.
The intern quickly added a urine test for this type of porphyria to her orders for the patient. He was planning to go to the lab when he came back for his next clinic visit the following week.
Hunting for Triggers
As Dr. White and Dr. Duah read up on P.C.T., a new question arose. Why would this man get the disease? It can be inherited – but the vast majority of those with P.C.T. get it from something else.
The most common cause is hepatitis C, a blood-borne virus that attacks the liver. Up to half of all those with P.C.T. also have hepatitis C. Getting rid of the virus gets rid of the P.C.T. Had this man been tested for hepatitis C? Yes. He didn’t have it.
Agent Orange, a toxic herbicide used extensively in the Vietnam War, has been linked to P.C.T. He was a Vietnam-era vet. But never exposed to Agent Orange.
Another trigger of P.C.T. was hemochromatosis. About one person in 250 has this inherited disorder, and the deposition of the iron in the liver that results can cause this type of porphyria.
Dr. Duah immediately thought back to her first impression of the patient. She’d noted then that he was remarkably tanned for the season. She asked him if he had just gotten back from a vacation someplace warm. He told her that he’d been camping and so she figured it was that. But what if she was seeing was the bronze component of hemochromatosis? She sat down and reviewed his chart.
Looking Back for Clues
One of the great things about working at the V.A. was that they had a fantastic electronic medical record that went back a good two decades. Sure enough, five years earlier, the patient had had a blood test measuring the iron in his blood. It was very high. The doctor who had seen him then had included it in her note, followed by an exclamation point. Still, the doctor didn’t seem to know what to do about it, because no further mention of it was made.
Dr. Duah hurried to show her discovery to Dr. White. And she ordered a blood test to look for the hemochromatosis genes.
By the time the patient came back to the V.A. clinic nearly a month later, the results of the tests he’d gotten showed that he did have hemochromatosis. The test for P.C.T. was still pending.
He saw Dr. Duah briefly, and then the dermatologist. After looking at his hands and reviewing the labs that had been done, the skin specialist was pretty certain that this was P.C.T.
Still, it would be nice to confirm the diagnosis. There was a test they could do right in the office. It wasn’t the best test, because it missed many of those who had some type of porphyria. But if it was positive, you could be sure the patient had some form of the disease.
The dermatologist asked the patient to give a urine sample. Sometimes the hemoglobin breakdown products, known as porphyrins, would turn purple when exposed to sunlight.
Deep in the bowels of the hospital, sunlight was hard to come by. But if the urine was seen under a special type of light known as a Wood’s lamp, it would take on a pink/orange fluorescence. Normal urine glowed blue under the blue Wood’s lamp.
He put the cup of urine under the special light. Sure enough, it glowed orange.
How the Patient Is Faring
The patient had P.C.T., caused by his newly discovered hemochromatosis. He’s now seeing a hematologist to get treated for the hemochromatosis, and a genetics counselor to discuss what having this inherited disease could mean for his now grown children.
He’s using sunscreen before he goes outside, and that’s already reduced the frequency of the blisters. His plan is to get rid of his excess iron by having the lab take a pint of blood every few weeks; removing the blood gets rid of the excess iron. It’s important to get rid of as much of the iron as he can to keep it from doing any more damage.
He wished that he could give the blood to the Red Cross. Why shouldn’t his treatment also help someone else? Alas, the Red Cross is not allowed to take it because of his disease.
It’s amazing, though, he said to me thoughtfully, that a little thing like a blister – as annoying as they were – should lead to all this.