Skin Disease harbinger

Attuned to the Signs of Trouble

Dermatologists specialize in diseases of the skin, but can also find clues to diabetes, cancer—and even COVID-19

It’s probably safe to say that when people think of television doctors dramatically saving lives, they rarely envision dermatologists. But many experienced dermatologists have tales of doing just that. Arianne Shadi Kourosh, an HMS assistant professor of dermatology who serves as director of community health in the Department of Dermatology at Massachusetts General Hospital and is founding director of the hospital’s Multi-Ethnic Skin and Pigmentary Disorders Program, once diagnosed a woman’s endometrial cancer based on an unusual rash, and Esther Freeman, MD ’09, an HMS assistant professor of dermatology and the director of Global Health Dermatology at Mass General, caught a relatively early-stage ovarian cancer by putting together a collection of subtle symptoms including muscle weakness, a purple rash on the patient’s eyelids, and a slight “shawl sign,” or redness around the neck. “None of these things mean much separately,” Freeman says, “but together they can add up to dermatomyositis, an inflammatory autoimmune condition associated with a six-fold risk of cancer.”

The language of skin

There haven’t been many studies on skin complaints in primary care, but a 2001 retrospective review of patient charts published in the Journal of the American Academy of Dermatology found that about 36 percent of patients coming to the University of Miami’s general medicine clinic over a two-year period presented with at least one skin problem, which for 60 percent of those patients was their primary complaint. And yet, say experts, dermatology gets short shrift in medical schools. Freeman recalls receiving “exactly one day” of training before her residency.

portrait of Esther Freeman, MD
Esther Freeman

“If more than one-third of patients have a skin care complaint and in medical school you’re only getting a few days of dermatological training,” says Freeman, “it’s a mismatch. My primary care colleagues have a hard job and have to know a lot about many different aspects of medicine, but we’re not preparing our workforce for the burden of conditions they’re going to see.”

There are “literally thousands of internal diseases, in all specialties, that can manifest on the skin,” according to Joseph Loscalzo, head of the Department of Medicine at Brigham and Women’s Hospital. Even the novel coronavirus turned out to have cutaneous manifestations.

About a month into the pandemic, doctors started noticing that some patients with COVID-19 who were otherwise asymptomatic exhibited purplish or dark red inflammation on their fingers and toes similar to what occurs with chilblains. The condition came to be known as “COVID toe.” It’s not the only cutaneous manifestation of SARS-CoV-2 , says Freeman. Others include a measleslike rash, hives, and, on the legs, a lacy pattern of lesions akin to the reddish-blue discolorations of livedo reticularis.

Freeman started an international registry to record dermatologic manifestations of COVID-19. It now has more than one thousand cases from thirty-eight countries. Data from this registry has helped identify symptoms specific to COVID-19, which, in turn, has contributed to including skin signs in testing criteria for the disease.

Freeman has presented the findings on skin signs to teams of physicians who are caring for COVID-19 patients. Following one such presentation, Freeman says, “I received an email from an infectious disease physician telling me she had a patient present with a new rash. Based on the skin findings for COVID-19, she had the patient tested—and received a positive result.”

“If recognizing these signs and testing people for the disease can help avert viral transmissions,” she adds, “well, that’s a win.”

A window within

As the body’s largest organ, skin both reflects what a person is exposed to in the environment and reveals what is happening internally. Even as it modulates and mirrors the immune system through lymphocytes, mast cells, and an immune activation system called the dendritic cell network, the skin’s ubiquitous blood vessels can also be a “window to internal disorders,” says Loscalzo.

Tiny yet prominent bright red veins known as venules, for instance, can indicate a hereditary hemorrhagic disease called telangiectasia, which can cause gastrointestinal bleeding and abnormal tangles of blood vessels connecting arteries and veins. Inflammatory vasculitis occurs when the immune system mistakenly attacks blood vessels and can signal hepatitis, rheumatoid arthritis, or lupus. And the blood or lymphatic systems can carry metastatic cells from breast, lung, colon, and other cancers to the skin where they can appear as a form of melanoma, carcinoma erysipeloides, and other malignant ulcerations.

“People have a misconception about dermatology,” says Lynn McKinley-Grant, MD ’80, who is the president of the Skin of Color Society, an associate professor at Howard University College of Medicine, and former vice chair for diversity and community engagement in the Department of Dermatology at Duke University School of Medicine. “They’re not aware that dermatologists work with so many complex medical patients,” she notes. “My decision to become a dermatologist was based on an awareness that the skin reflects health and disease in the whole patient.”

Acne, eczema, vitiligo, and other visible skin diseases can increase the likelihood of depression.

An example from her residency illustrates McKinley-Grant’s point, “A thin, elderly African American man presented with weight loss, severe anemia, and trace blood in his stool. His normally darker skin type had paled to a gray brown, and he had a rock-hard cyst on his forehead. We determined he had Gardner’s syndrome, a type of hereditary polyposis of the colon that is associated with bone growths, epidermal cysts, and colon cancer.”

Signs and signifiers

Dermatologists don’t just look at the skin, but also at hair, nails, eyes, and oral and genital mucosa to make their diagnoses. Skin can show signs of liver and kidney disease, malabsorption and nutritional deficiencies, and endocrinopathies and gastrointestinal disorders. Ridges on the nails can be read like the rings on a tree, often appearing as a side effect of chemo treatments, heart attack, or infections like mumps or coxsackievirus. The patchy loss of skin color that characterizes vitiligo can presage thyroid disease as surely as can more typical symptoms like thinning hair and brittle nails. Dermatitis herpetiformis—chronic itchy, blistered skin—affects about 10 percent of people with celiac disease, and while flushing can be benign, as it usually is in menopausal women, for example, it may also hint at serious hormonal disorders or cardiovascular issues.

And that’s one problem with diagnosing through cutaneous signs: While some indications of internal disease are unusual enough that physicians immediately refer patients to a specialist, many skin-related symptoms seem so common and mild that they don’t warrant alarm. Examples include the painful, raised lesions known as Osler’s nodes, Janeway lesions on the palms and soles, and reddish-brown splinter hemorrhages, which may not be seen often in general practice but are associated with endocarditis, among other conditions.

“My decision to become a dermatologist was based on an awareness that the skin reflects health and disease in the whole patient.”

“Skin signs can be good at telling you something’s going on but not necessarily at telling you what is going on,” says Jeremy Beaulieu, a nurse practitioner at Joslin Diabetes Center. “Also, many skin lesions will resolve on their own without any intervention.” The ambiguous and vague nature of dermatological symptoms, along with mercurial appearances and disappearances, may contribute to diabetes diagnoses often lagging behind symptoms by a decade or more. Necrobiosis lipoidica and acanthosis nigricans can be clear-cut warnings of insulin resistance, but less obvious is itchy skin, says Beaulieu. “Ninety-nine percent of the time, you’re itching because the air is dry,” he points out. “Health care professionals might advise patients first to try a moisturizer, but it’s important to follow up if that’s not working.”

Psoriasis, too, is a common skin condition that research conducted in the past decade has shown is associated with lung cancer and lymphoma. In women, psoriasis and psoriatic arthritis have been linked with Crohn’s disease, osteoporosis, and inflammatory bowel disease.

Psoriasis can signal not only an internal illness but also can be associated with its occurrence. A 2018 literature review in Cureus, for instance, considered the causal relationship between psoriasis and cardiovascular disease. 

portrait of Lynn McKinley-Grant, MD
Lynn McKinley-Grant
 

“A lot of recent studies show that the chronic inflammation of psoriasis can put people at higher risk for cardiovascular disease, especially in people with comorbidities such as smoking, obesity, and diabetes,” says McKinley-Grant.

Acne, eczema, vitiligo, and other visible skin diseases can themselves increase the likelihood of depression. “Doctors sometimes brush them off, but skin diseases can be really debilitating for patients,” says Kourosh. “Even in cases where they’re not ‘dangerous,’ some diseases are so marginalizing they can ruin someone’s life and make them hide from society and even become suicidal.”

Mind-body connections

Many patients with psychological and psychiatric disorders can show skin signs that are clues to their illnesses. This can be true for a range of mental illnesses, including obsessive compulsive disorders, delusions of parasitosis, self-mutilation, eating disorders, phobias, depression, and bipolar disorder.

These links have embryologic roots, McKinley-Grant points out. As human embryos develop, the neurons of the brain, the pigment cells of the skin, and the epidermis, or outer layer of skin, all derive from the layer of embryonic cells known as the ectoderm. Understanding this relationship highlights the importance of distinguishing the fundamental cause of a skin finding, she says, and underscores how vital it is to really look at a patient.

“Doctors spend less time observing live patients, and they spend more time looking at the e-patient in an electronic medical record on the computer,” says McKinley-Grant.

Freeman notes that some skin manifestations of disease simply aren’t on physicians’ radar. Patients with AIDS, for instance, overwhelmingly report cutaneous symptoms, but those symptoms are not always as obvious as one might think. “Even in Africa,” she says, “where doctors are dealing with more cases of HIV and AIDS and routinely seeing Kaposi’s sarcoma, it can be hard to diagnose without access to skin biopsies. It turns out that when we use clinical judgment alone, we are wrong about a third of the time. There are a lot of KS mimickers.”

Similarly, in this country, dermatologists are “having to reeducate our colleagues on the cutaneous signs of measles, mumps, and other reemerging diseases in this era of nonvaccinators,” says Kourosh. “An aggressive form of hand, foot, and mouth  disease made a terrible recurrence a few years ago.”

Text revisions

A further complication to correct diagnosis is that many medical textbooks and online guides have not always included darker skin tones in their photographs and descriptions. “We’re still far from reaching parity,” says Kourosh. “Unless a person happened to train in a hospital system that’s extremely diverse, it’s very hit or miss whether they’ll be trained on all skin colors.” This is especially important because there are disorders that disproportionately affect people with dark skin.

Medical textbooks and online guides have not always included darker skin tones in their photographs.

Although the problem is slowly being addressed, McKinley-Grant says it is crucial that health care providers are trained in recognizing diseases—and subtle changes—in all skin types.

“Almost every mother, regardless of the ethnicity or age of her child, can tell when they are pale and not feeling well,” she says. “The underlying hues of the skin are not only the result of the presence of melanin, but also reflect red blood cell counts and oxygen levels—measures that are vital signs for all humans. We need to train our health care providers to recognize changes in hue in all skin types, including the skin of Black and brown people.”

“When we invite people for lectures or to contribute to a textbook or health care literature,” she adds, “we need to start making it almost mandatory that they show a diversity of ethnicity and skin color in the presentation, with images of disease in black and brown skin.”

Rashes that may look red on a light-skinned patient tend to appear darker brown or purple on brown or black skin. Anemia appears as gray on dark skin rather than ghostly pale on light skin, while the darkening of skin associated with hyperpigmentation, itself a sign of Addison’s disease and other conditions, may go unnoticed on dark skin. For inflammation, says McKinley-Grant, it’s important to ask the patient where the warmth and pain is and whether the area in question looks like their normal skin color.

Dermatologists also discern problems in people with darker skin tones by looking for patterns. “Pattern recognition is a huge part of our training,” says Freeman. “We get 12,000 to 16,000 hours of supervised patient care. That allows us to learn to recognize patterns. So if you see a pattern but don’t know how to interpret it, call a dermatologist.”

Future vision

That may be easier said than done these days. Since 1999, American Academy of Dermatology surveys have steadily shown that skin doctors themselves report there are not enough of them to go around, especially with the increasing demands on the profession as a result of population aging and rising rates of skin cancer and other cutaneous diseases.

Dermatology is one of the highest paying fields of medicine, and it has one of the lowest burnout rates. The ever-increasing market for cosmetic dermatology—which is paid for out-of-pocket—has put an even greater burden on residency programs.

“At Harvard, 70 percent of our residents stay in medical or academic dermatology,” says Freeman, “but we’re probably the only school in the country with that statistic. Not everyone who wants to is able to match into the field, and these are really good students. It’s common to take a year off from medical school and do a year of dermatological research just to get in.”

Many schools are combining residencies in internal medicine and dermatology. “Dermatologists look at a rash and then develop a differential diagnosis, then ultimately get a history,” says Loscalzo. “Internists do just the opposite, gathering a lot of history, looking at all aspects of the patient’s physical exam, and then trying to correlate what’s going on with the skin to what’s happening internally. It’s a totally different heuristic, and a combined residency is a great way to learn both worlds.”

“To train AI at high levels of accuracy, you need an enormous collection of photos, and even the largest dermatology photo libraries don’t have standardized diagnoses where a group of dermatologists agree.”

Continuing medical education, workshops, and events like Mass General’s annual Dermatology Bootcamp, hosted by Kou­rosh, are helping to bridge the gap. “Through programs like this, dermatologists at HMS are always more than ready to teach and give lectures to other providers and trainees in our hospital system and the community,” Kourosh says.

In addition, the use of telehealth has helped extend expertise. Although its use increased 53 percent between 2016 and 2017, according to a 2019 article from the American Medical Association, its use has expanded again. Earlier this year, the AMA detailed extensive changes to telehealth, all allowed for in the Coronavirus Aid, Relief, and Economic Security Act of 2020. Among those changes: expanding the list of services that can be delivered remotely, ensuring payment of physician fees for those services, and updating the requirements for accessing remote care to permit physicians to conduct telehealth visits from their homes—and patients to access them from theirs.

These changes have been especially useful for dermatology and are increasing access to health care in all specialties, particularly for underserved patients in rural areas and elsewhere, for members of the military, and, during this pandemic, for patients sheltering in place, says McKinley-Grant.

Apps and artificial intelligence also hold promise, though, according to Kourosh and others they have a long way to go. “To train AI at high levels of accuracy,” Kourosh says, “you need an enormous collection of photos, and even the largest dermatology photo libraries don’t have standardized diagnoses where a group of dermatologists agree.” Add to that the dearth of patients of color represented in most collections. “Multiple efforts are being made now to do this correctly and safely for patients, but it may take years,” she adds.

Until then, internists, primary care doctors, and other specialists remain patients’ first line of defense. “It’s true that time is a bigger limitation than in the past,” admits Loscalzo, “but if you’re not carefully considering skin symptoms, you’re not being a thorough physician.”

Elizabeth Gehrman is a Boston-based writer.

Images: Juti/Essentials Collection/Getty Images (top); John Soares (Freeman); Mark Finkenstein (McKinley-Grant)