Erythema Nodosum

Erythema nodosum

Erythema Nodosum | Johns Hopkins Medicine

Erythema nodosum is an inflammatory disorder. It involves tender, red bumps (nodules) under the skin.

This picture shows reddish-purple, hard (indurated), painful nodules (erythema nodosum) that occur most commonly on the shins. These lesions may be anywhere on the body and may be associated with tuberculosis (TB), sarcoidosis, coccidioidomycosis, systemic lupus erythematosis (SLE), fungal infections, or in response to medications.

This person has erythema nodosum nodules on the feet. The feet are red and painful. This disorder may be associated with drugs or infections.

In about half of cases, the exact cause of erythema nodosum is unknown. The remaining cases are associated with an infection or other systemic disorder.

Some of the more common infections associated with the disorder are:

Erythema nodosum may occur with sensitivity to certain medicines, including:

  • Antibiotics, including amoxicillin and other penicillins
  • Sulfonamides
  • Sulfones
  • Birth control pills
  • Progestin

Sometimes, erythema nodosum may occur during pregnancy.

Other disorders linked to this condition include leukemia, lymphoma, sarcoidosis, rheumatic fever, Bechet disease, and ulcerative colitis.

The condition is more common in women than it is in men.

Erythema nodosum is most common on the front of the shins. It may also occur on other areas of the body such as buttocks, calves, ankles, thighs, and arms.

The lesions begin as flat, firm, hot, red, painful lumps that are about 1 inch (2.5 centimeters) across. Within a few days, they may become purplish in color. Over several weeks, the lumps fade to a brownish, flat patch.

Other symptoms may include:

  • Fever
  • General ill feeling (malaise)
  • Joint aches
  • Skin redness, inflammation, or irritation
  • Swelling of the leg or other affected area

Your health care provider can diagnose this condition by looking at your skin. Tests that may be done include:

  • Punch biopsy of a nodule
  • Throat culture to rule out a strep infection
  • Chest x-ray to rule out sarcoidosis or tuberculosis
  • Blood tests to look for infections or other disorders

The underlying infection, drug, or disease should be identified and treated.

Treatment may include:

  • Nonsteroidal anti-inflammatory drugs (NSAIDs).
  • Stronger anti-inflammatory medicines called corticosteroids, taken by mouth or given as a shot.
  • Potassium iodide (SSKI) solution, most often given as drops added to orange juice.
  • Other oral medicines that work on the body's immune system.
  • Pain medicines (analgesics).
  • Rest.
  • Raising the sore area (elevation).
  • Hot or cold compresses to help reduce discomfort.

Erythema nodosum is uncomfortable, but not dangerous in most cases.

Symptoms most often go away within about 6 weeks, but may return.

Call your provider if you develop symptoms of erythema nodosum.

Forrestel A, Rosenbach M. Erythema nodosum. In: Lebwohl MG, Heymann WR, Berth-Jones J, Coulson IH, eds. Treatment of Skin Disease: Comprehensive Therapeutic Strategies. 4th ed. Philadelphia, PA: Elsevier; 2018:chap 75.

Gehris RP. Dermatology. In: Zitelli BJ, McIntire SC, Nowalk AJ, eds. Zitelli and Davis' Atlas of Pediatric Diagnosis. 7th ed. Philadelphia, PA: Elsevier; 2018:chap 8.

James WD, Elston DM, Treat JR, Rosenbach MA. Diseases of the subcutaneous fat. In: James WD, Elston DM, Treat JR, Rosenbach MA, Neuhaus IM, eds. Andrews' Diseases of the Skin: Clinical Dermatology. 13th ed. Philadelphia, PA: Elsevier; 2020:chap 23.

Last reviewed on: 7/12/2019

Reviewed by: Michael Lehrer, MD, Clinical Associate Professor, Department of Dermatology, University of Pennsylvania Medical Center, Philadelphia, PA. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team.

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Erythema Nodosum

Erythema Nodosum | Johns Hopkins Medicine

Linkedin Pinterest Rashes and Skin Inflammation

Erythema nodosum is characterized by tender, red bumps, usually found symmetrically on the shins. Up to 55 percent of cases have no clear identifiable cause. Sometimes, erythema nodosum is not a separate disease. Rather, it is a sign of some other infection, disease, or of a sensitivity to a drug.

Diseases that can cause erythema nodosum

These diseases include:

  • Streptococcal infections
  • Sarcoidosis (inflammation of the lymph nodes and other organs)
  • Coccidioidomycosis (infection of the upper respiratory tract and lungs)
  • Histoplasmosis (an infectious pulmonary disease)
  • Tuberculosis
  • Psittacosis (a flu- disease)
  • Ulcerative colitis or Crohn's disease
  • Cancer
  • Pregnancy

Medicines that can cause erythema nodosum

These medicines include:

  • Antibiotics containing sulfa or penicillin
  • Bromides
  • Iodides
  • Oral contraceptives

What are the symptoms of erythema nodosum?

The following are the most common symptoms of erythema nodosum. However, each individual may experience symptoms differently. Symptoms may include:

  • Red, tender bumps on the shins
  • Fever
  • Joint pain
  • Enlarged lymph nodes in the chest

Young adults are particularly susceptible to erythema nodosum. The symptoms of erythema nodosum may resemble other skin conditions. Always talk with your healthcare provider for a diagnosis.

How is erythema nodosum diagnosed?

A biopsy (removal of tissue for exam under a microscope) of a bump can usually confirm the diagnosis. The biopsy is done along with complete lab work. However, the exact cause cannot always be identified. Erythema nodosum caused by medicine can usually be diagnosed by elimination of the medicine causing the reaction. A throat swab may be done to check for strep infection. 

Treatment for erythema nodosum

Specific treatment for erythema nodosum will be discussed with you by your healthcare provider :

  • Your age, overall health, and medical history
  • Extent of the condition
  • Your tolerance for specific medicines, procedures, or therapies
  • Expectations for the course of the condition
  • Your opinion or preference

Treatment may include:

  • Antibiotics to treat an underlying bacterial infection
  • Treatment of other underlying cause
  • Bed rest (to relieve pain)
  • Nonsteroidal anti-inflammatory medicines
  • Oral corticosteroids

Although erythema nodosum is uncomfortable, it is usually not a serious condition. Symptoms are usually gone within 6 weeks. However, they may appear again.  


Lupus-Specific Skin Disease and Skin Problems

Erythema Nodosum | Johns Hopkins Medicine

Most people with lupus experience some sort of skin involvement during the course of their disease. In fact, skin conditions comprise 4 of the 11 criteria used by the American College of Rheumatology for classifying lupus. There are three major types of skin disease specific to lupus and various other non-specific skin manifestautions associated with the disease.

Lupus-Specific Skin Disease

Three forms of specific skin disease occur in people with lupus, and it is possible to have lesions of multiple types.

In addition, a person can also have one of the three forms outlined below without actually having full-blown systemic lupus erythematosus (SLE), but the presence of one of these disease forms may increase a person’s risk of developing SLE later in life.

Usually, a skin biopsy is used to diagnose forms of cutaneous lupus, and various medications are available for treatment, including steroid ointments, corticosteroids (e.g., prednisone), and antimalarials (e.g., Plaquenil).

Chronic Cutaneous Lupus Erythematosus (CCLE) / Discoid Lupus Erythematosus (DLE)

Chronic cutaneous (discoid) lupus erythematosus is usually diagnosed when someone exhibits signs of lupus in the skin. People with SLE can also have discoid lesions, and about 5% of all people with DLE will develop SLE later in life.

A skin biopsy is used to diagnose this condition, and the lesions have a characteristic pattern known to clinicians: they are thick and scaly, plug the hair follicles, appear usually on surfaces of the skin exposed to sun (but can occur in non-exposed areas), tend to scar, and usually do not itch.

If you are diagnosed with discoid lupus, you should try to avoid sun exposure when possible and wear sunscreen with Helioplex and an SPF of 70 or higher. In addition, you doctor may prescribe medications to help prevent and curb inflammation, including steroid ointments, pills, or injections , antimalarial medications such as Plaquenil, and/or immunosuppressive medications.

Subacute Cutaneous Lupus Erythematosus (SCLE)

About 10% of lupus patients have SCLE. The lesions characteristic of this condition usually do not scar, do not appear thick and scaly, and usually do not itch. About half of all people with SCLE will also fulfill the criteria for systemic lupus.

Treatment can be tricky because SCLE lesions often resist treatments with steroid creams and antimalarials.

People with SCLE should be sure to put on sunscreen and protective clothing when going outdoors in order to avoid sun exposure, which may trigger the development of more lesions.

Acute Cutaneous Lupus Erythematosus (ACLE)

Most people with ACLE have active SLE with skin inflammation, and ACLE lesions are found in about half of all people with SLE at some point during the course of the disease.

The lesions characteristic of ACLE usually occur in areas exposed to the sun and can be triggered by sun exposure.

Therefore, it is very important that people with ACLE wear sunscreen and protective clothing when going outdoors.

Malar Rash

About half of all lupus patients experience a characteristic rash called the malar or “butterfly” rash that may occur spontaneously or after exposure to the sun. This rash is so-named because it resembles a butterfly, spanning the width of the face and covering both cheeks and the bridge of the nose.

The malar rash appears red, elevated, and sometimes scaly and can be distinguished from other rashes because it spares the nasal folds (the spaces just under each side of your nose). The butterfly rash may appear on its own, but some people observe that the appearance of the malar rash indicates an oncoming disease flare.

Whatever the case, it is important to pay attention to your body’s signals and notify your physician of anything unusual.


50% of all people with lupus experience sensitivity to sunlight and other sources of UV radiation, including artificial lighting. For many people, sun exposure causes exaggerated sunburn- reactions and skin rashes, yet sunlight can precipitate lupus flares involving other parts of the body. For this reason, sun protection is very important for people with lupus.

Since both UV-A and UV-B rays are known to cause activation of lupus, patients should wear sunscreen containing Helioplex and an SPF of 70 or higher. Sunscreen should be applied everywhere, including areas of your skin covered by clothing, since most clothing items contain an SPF of only about 5.

Be sure to reapply as directed on the bottle, since sweat and prolonged exposure can cause coverage to dissipate.

Livedo reticularis

People with lupus may experience a lacy pattern under the skin called livedo reticularis. This pattern may range anywhere from a violet web just under the surface of the skin to something that looks a reddish stain.

Livedo can also be seen in babies and young women, is more prominent on the extremities, and is often accentuated by cold exposure.

The presence of livedo is usually not a cause for alarm, but it can be associated with antiphospholipid antibodies.


About 70% of people with lupus will experience hair loss (alopecia) at some point during the course of the disease. Hair loss in lupus is usually characterized by dry, brittle hair that breaks, and hair loss is more common around the top of the forehead. Physical and mental stress can also cause hair loss, as can certain medications, including corticosteroids such as prednisone.

In many cases the hair will grow back, but hair loss due to scarring from discoid skin lesions may be permanent. There is no cure-all for hair loss, but treatments such as topical steroids and Rogaine may be prescribed. Sometimes dealing with the cosmetic side effects of lupus can be difficult, but some people find using hairpieces and wigs to be an effective means of disguising hair loss.

Oral and Nasal Ulcers

About 25% of people with lupus experience lesions that affect the mouth, nose, and sometimes even the eyes. These lesions may feel small ulcers or “canker sores.

” Such sores are not dangerous but can be uncomfortable if not treated.

If you experience these types of lesions, your doctor may give you special mouthwash or Kenalog in Orabase (triamcinolone dental paste) to help expedite the healing process.

Raynaud’s Phenomenon

Approximately one-third of all people with lupus experience a condition called Raynaud’s phenomenon in which the blood vessels supplying the fingers and toes constrict. The digits of people with Raynaud’s are especially susceptible to cold temperatures.

Often people with the condition will experience a blanching (loss of color) in the digits, followed by blue, then red discoloration in temperatures that would only be mildly uncomfortable to other people (such as a highly air-conditioned room).

It is very important that people with Raynaud’s wear gloves and socks when in air-conditioned spaces or outside in cool weather. Hand warmers used for winter sports (e.g., Hot Hands) can also be purchased and kept in your pockets to keep your hands warm.

These measures are very important, since Raynaud’s phenomenon can cause ulceration and even tissue death of the fingers and toes if precautions are not taken. People have even lost the ends of their fingers and toes due to the poor circulation involved in Raynaud’s phenomenon.

Cigarettes and caffeine can exacerbate the effects of Raynaud’s, so be sure to avoid these substances. If needed, your doctor may also recommend a calcium channel blocker medication such as nifedipine or amlodipine to help dilate your blood vessels.

Hives (Urticaria)

About 10% of all people with lupus will experience hives (urticaria). These lesions usually itch, and even though people often experience hives due to allergic reactions, hives lasting more than 24 hours are ly due to lupus.

If you experience this condition, be sure to speak with your doctor, since s/he will want to be sure that the lesions are not caused by some other underlying condition, such as vasculitis or a reaction to medication.

Your doctor will probably distinguish these lesions from those caused by vasculitis by touching them to see if they blanch (turn white).


Approximately 15% of people with lupus will experience purpura (small red or purple discolorations caused by leaking of blood vessels just underneath the skin) during the course of the disease. Small purpura spots are called petechiae, and larger spots are called eccymoses. Purpura may indicate insufficient blood platelet levels, effects of medications, and other conditions.

Cutaneous Vasculitis

Some people with lupus may develop a condition known as cutaneous vasculitis, in which the blood vessels near the skin experience inflammation that ultimately restricts blood flow. This condition can cause hive- lesions on the skin that may itch and do not turn white when depressed.

Other skin abnormalities may also be present, including actual gangrene of the digits. If left untreated, vasculitic lesions may cause ulceration and necrosis (cell death), and dead tissue must be surgically removed. Rarely, fingers or toes with aggressive ulceration and gangrene may require amputation.

Therefore, it is very important that you notify your doctor of any skin abnormalities.


DDW: Uveitis significantly more common in black patients with IBD

Erythema Nodosum | Johns Hopkins Medicine

WASHINGTON – Black patients with inflammatory bowel disease were significantly more ly to have at least one extraintestinal manifestation of the disease than were white patients, particularly uveitis, in a study of more than 500 people with Crohn’s disease or ulcerative colitis, Dr. Jemilat Badamas reported at the annual Digestive Disease Week.

Black patients were about twice as ly to have uveitis than were white patients in the study, after researchers controlled for other risk factors for extraintestinal manifestations of IBD, said Dr.

Badamas, a gastroenterology fellow at Johns Hopkins University, Baltimore.

these results, and the increased rate of uveitis among black IBD patients seen in other studies, “practitioners should consider proactive referral of African-Americans [with IBD] to be screened for uveitis,” she said.

The study compared the incidence of various extraintestinal manifestations of IBD among 196 black patients and 342 white patients with a confirmed diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC), which included uveitis, small and large joint disease, sacroiliitis, ankylosing spondylitis, episcleritis, pyoderma gangrenosum (PG), erythema nodosum (EN), and progressive sclerosing cholangitis, confirmed in the medical records. All the patients had been treated at outpatient gastroenterology clinics and infliximab infusion clinics at Johns Hopkins Hospital, including patients who were hospitalized and were subsequently followed up at the GI clinics. Cases with no information on extraintestinal manifestations were excluded.

Enrollment of all patients at one medical center overcame one of the limitations of previous studies evaluating racial differences in extraintestinal manifestations of IBD, where most of the black and white patients were treated in different centers, so researchers could not account for differences in practices at different institutions or access to subspecialty care, she pointed out.

In the Johns Hopkins study, patients in both groups were diagnosed with IBD at a mean age of 28-29 years. Among the black patients, 62% were female and they were enrolled in the study at a mean age of 38 years.

Among the white patients, half were female and they were enrolled at a mean age of 41 years.

The data on these patients are being collected as part of the Multicenter African American Inflammatory Bowel Disease Study (MAAIS).

More black patients (41%) had at least one extraintestinal manifestation of IBD compared with white patients (33%). The most common was large joint disease, affecting 25.5% of black patients and 19% of white patients, Dr. Badamas said.

Uveitis was more common in black patients (6.9% vs. 2.7%), a difference that was statistically significant (P = 0.021). Pyoderma gangrenosum was more common in black patients (4.8% vs. 1.

8%), a difference of borderline significance (P = 0.051).

After the researchers controlled for gender, disease location, and extent of disease, which are factors known to be associated with extraintestinal manifestations of IBD, there were no significant differences between the two groups for most of the manifestations, she said. But black patients were about two times more ly to have uveitis, compared with white patients (odds ratio, 2.3), and were 1.5 times more ly to have at least one extraintestinal manifestation (OR, 1.5), she added.

The study did not include a temporal analysis to determine if any of these manifestations occurred before the diagnosis of IBD was made, but Dr. Badamas said that most were diagnosed after the diagnosis of IBD.

Dr. Badamas had no relevant disclosures.

[email protected]


COVID-19 Tip Sheet: Story Ideas from Johns Hopkins

Erythema Nodosum | Johns Hopkins Medicine

Newswise — From The Front Lines: A Thank You from Johns Hopkins All Children's Hospital Physician Meghan Martin, M.D.

It seems there will never be enough “thank-you’s” for the incredible doctors, nurses technicians and support staff who are working around the clock to help patients with this dangerous disease. It is their dedication, determination and spirit that allow Johns Hopkins to deliver the promise of medicine.

Meghan Martin, M.D., is an emergency medicine physician at Johns Hopkins All Children’s Hospital. In her role, she cares for some of Johns Hopkins’ youngest patients. Martin is available to speak with the press about the changes she’s had to make in patient care as the COVID-19 pandemic persists.

New App Aims to Spot COVID-19 Outbreaks

The COVID-19 tracker app is part of a research trial

Identifying the next COVID-19 outbreak may seem impossible to predict, but a new app that collects body temperature recordings may give researchers advance warning of an impending hotspot of illness.

The app, available through Google Play and the Apple App Store, asks users to record their body temperature and respond to questions about key COVID-19 symptoms. The anonymized data is linked to a randomly generated ID and stored on a secure server. Temperature and symptom data are mapped geographically to provide a display of anomalies occurring across the country.

“This type of data tracking could be really useful to enable targeted large-scale testing efforts,” says Robert Stevens, M.D.

, associate professor of anesthesiology and critical care medicine at the Johns Hopkins University School of Medicine.

“It could allow us to identify beforehand areas that are at increased or decreased risk and inform decisions regarding mitigation and lifting social distancing restrictions.” 

Stevens worked with epidemiologist Frank Curriero, of Johns Hopkins University’s Bloomberg School of Public Health, and electrical and computer engineer Ralph Etienne-Cummings, of the Whiting School for Engineering, to develop the app, which they dubbed “COVID Control — A Johns Hopkins University Study.”

The team will analyze the data collected to identify unexplained increases in body temperatures and generate real-time risk estimates of potential COVID-19 outbreaks. This predictive tool will allow health care systems and government agencies to better deploy resources to mitigate the effects of the disease.

Stevens is available to discuss this research trial.

Find more information on COVID Control here. And, read a recent article about the app in the HUB.

Obesity Linked to Severity of COVID-19 Infection in Younger Adults

As the COVID-19 pandemic was initially spreading, data from China and Italy suggested that only about 15% of people under the age of 50 were being hospitalized. However, when the disease reached the United States, physicians anecdotally noted what seemed an uptick in the number of younger patients with disease serious enough to require intensive care.

Although preexisting conditions such as heart disease, diabetes or high blood pressure have been linked to greater susceptibility to the virus, obesity wasn’t on the radar as a risk factor early in the coronavirus outbreak.

That’s because only about 6% of Chinese people and 20% of Italians are obese.

The United States, on the other hand, has a 40% rate of obesity in adults, making researchers wonder if this might factor into the younger population’s showing up with severe disease.

In a new correspondence published on April 30, 2020, in The Lancet, Johns Hopkins researchers examined the link between age and obesity of American patients with COVID-19 hospitalized in intensive care units (ICUs).

Seventy-five percent of the patients had a body mass index (BMI) of 26 or greater, indicating the person as overweight; and 25% had a BMI higher than 35, designating the person as morbidly obese. In general, they found that those patients in the ICU that were younger had higher BMIs, suggesting that younger Americans with obesity are ly at greater risk from COVID-19.

The researchers say that young people should pay attention to social distancing and stay vigilant about when to seek medical treatment in the early stages of their disease to help reduce the risks.

The first author, David Kass, M.D., the Abraham and Virginia Weiss Professor of Cardiology at the Johns Hopkins University School of Medicine, is available to discuss the implications of his findings.

Be Aware of Lyme Disease Risks in The Midst of the COVID-19 Pandemic

Spring and summer are the highest risk seasons for contracting Lyme disease from the bite of an infected deer tick.

With most of the country staying at home and social distancing, due to the COVID-19 pandemic, people are spending more time in their gardens and on walks in their neighborhoods and nearby woods — potentially putting them at higher risk for Lyme disease.

There are over 300,000 new cases of Lyme disease reported each year in the United States. Daily practices are important in disease prevention.

Hand-washing is recognized as being helpful in preventing COVID-19. wise, daily tick checks are helpful in avoiding Lyme disease. Another effective Lyme disease tip is to treat clothing with tick pesticides, such as permethrin. It is important to take preventative measures as well as to recognize how early presentations of Lyme disease compare and contrast with those of COVID-19.

Flu- symptoms of fever, severe fatigue, malaise, chills, sweats, body/muscle aches and headaches, are present in early Lyme disease, as well as in early COVID-19.

Lyme disease can also present with a distinct large, expanding, bull’s eye-looking rash called erythema migrans, whereas COVID-19 rash presentations may include patchy red lesions that more resemble measles, chicken pox or frostbite. John Aucott, M.D.

, director of the Johns Hopkins Lyme Disease Research Center and associate professor of medicine at the Johns Hopkins University School of Medicine, is available to discuss prevention tips, as well as the clinical impact of Lyme disease and how to distinguish early Lyme disease signs and symptoms from COVID-19. Mark Soloski Ph.D.

, co-director for Basic Research for the Johns Hopkins Lyme Disease Research Center and professor of medicine at the Johns Hopkins University School of Medicine, is available to highlight details surrounding the immune response in Lyme disease and how it may be different from the response to COVID-19.

Don’t Skip Needed Care in Fear of COVID-19

With the stay-at-home measures and fear of catching the new coronavirus, people may be thinking twice before deciding what merits a visit to the doctor’s office, an urgent care clinic or the emergency room. There are ways to stay safe and protected when seeking needed care during the pandemic.

It’s important for people to continue to obtain care in-person or remotely when medical attention is needed, especially for those with preexisting or chronic conditions who require follow-up with a health care provider. Not getting care, particularly for chronic illnesses and urgent or emergency conditions, puts people at high risk for complications later.

These complications could end up being worse than the COVID-19 disease.

The following Johns Hopkins Medicine experts can address ways to stay safe during the pandemic, what to seek care for and why it’s important to follow up with a health care provider for certain conditions.

Heart Attackand Cardiovascular Issues

Erin Michos, M.D., M.H.S., Director of Women’s Cardiovascular Health

Stroke and Neurological Issues

Victor Urrutia, M.D., Director of the Johns Hopkins Hospital Comprehensive Stroke Center

Sickle Cell Anemia

Sophie Lanzkron, M.D., M.H.S., Director of the Sickle Cell Center for Adults at The Johns Hopkins Hospital

Older Adult Care

Alicia Arbaje, M.D., Ph.D., M.P.H., Director of Transitional Care Research at Johns Hopkins

Asthma and COPD

William Checkley, M.D., Ph.D., Associate Professor of Medicine


Kathleen Page, M.D., Associate Professor of Medicine

Emergency Medicine

Barbara Maliszewski, R.N., M.S., Assistant Director of Nursing, Department of Emergency Medicine

Tracking the Mental Health of Frontline Workers — and How Their Loved Ones Can Help

While the symptoms and effects of COVID-19 continue to develop in unexpected ways, the psychological patterns of frontline workers will follow a predictable pattern, according to Albert W. Wu, M.D., M.P.H.

, an internist at Johns Hopkins Medicine and director of the Center for Health Services and Outcomes Research. And, for many doctors and nurses treating coronavirus patients, “we’re at a dangerous point,” he says.

“We’ve gone past the honeymoon phase.”

The adrenalin surge and group cohesion that marked the initial response to the pandemic is giving way to discouragement, exhaustion and burnout among health care workers, explains Wu, a professor of health policy and management, who conducts research on staff support.

Wu is available to trace the emotional highs and lows of frontline workers in a crisis, as well as offer advice as to what their loved ones can do to help — from organizing family conference calls to acknowledging they can unknowingly add stress. “By supporting them, you are supporting the fight against COVID-19,” he says.

Making Sure Vulnerable Communities Have Access to Reliable Information and COVID-19 Care

For many in the Latino community “there’s absolutely no safety net,” says Kathleen Page, M.D., who serves a large population of immigrant patients. “We’re seeing a rise in COVID-19 cases among Latino immigrants, particularly those with limited English proficiency (LEP), who most ly are undocumented.”

To bridge the gap, Page was instrumental in setting up — with the Esperanza Center in Baltimore—a hotline for Spanish speakers. She is also providing information to the Latino community through Live chats, with support from Johns Hopkins Centro Sol and other community partners.

In addition, with collaboration from the Johns Hopkins Office of Diversity and Inclusion and the Office of Language Access Services, Page is establishing a bilingual provider consultation service to support the care of Spanish-speaking patients with LEP admitted to the Johns Hopkins Hospital and the Johns Hopkins Bayview Medical Center.

Her team is also assisting the Baltimore City Health Department with contact investigations in this community.

“We’re in the midst of setting up a Spanish provider care team that will be embedded within other care teams in the hospital, to help improve communication with Spanish speaking patients and their families.”

Page is available for interview on this topic.

Mitigating Issues in Senior Care Facilities

Infectious disease specialist Morgan J. Katz, M.D., M.H.S., says 60 to 70 percent of long-term care facility (assisted living and skilled nursing) residents are testing positive for COVID-19 but are asymptomatic when they are tested.

Katz is part of the Maryland Strike Team, a collaboration between the National Guard, Hospital Systems and the State that focuses efforts on stabilizing nursing homes struggling with COVID outbreaks by providing widespread testing, infection prevention recommendations and care delivery.

Maryland’s strike teams were formed after the confirmation that hundreds of elderly care facilities in Maryland have confirmed cases of COVID-19.

Katz is available to discuss what the team is doing; the next steps; and needs for widespread regular testing of long-term care facilities to reduce mortality and a large influx of nursing home residents into acute health care systems.

For information about the coronavirus pandemic from Johns Hopkins Medicine, visit the coronavirus information page. For information on the coronavirus from throughout the Johns Hopkins enterprise, including the Johns Hopkins Bloomberg School of Public Health and The Johns Hopkins University, visit the Coronavirus Resource Center.


Clinical, Serologic, and Genetic Factors Associated with Pyoderma Gangrenosum and Erythema Nodosum in Inflammatory Bowel Disease Patients

Erythema Nodosum | Johns Hopkins Medicine

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Pyoderma gangrenosum (PG) and erythema nodosum (EN) are the most common cutaneous manifestations of inflammatory bowel disease (IBD) but little is known regarding their etiopathogenesis.

We performed a case–control study comparing characteristics between IBD patients with a documented episode of PG (PG+) and/or EN (EN+) with those without PG (PG−) and EN (EN−).

Data on clinical features were obtained by chart review. IBD-related serology was determined using enzyme-linked immunosorbent assay and genome-wide data generated using Illumina technology.

Standard statistical tests for association were used.

We identified a total of 92 cases of PG and 103 cases of EN with genetic and clinical characteristics, of which 64 PG and 55 EN cases were available for serological analyses. Fewer male subjects were identified in the PG(+) (odds ratio 0.6, P = 0.009) and EN(+) groups (odds ratio 0.31, P = 0 < 0.0001).

Colonic disease, previous IBD-related surgery, and noncutaneous extra-intestinal manifestations were more common among both PG(+) and EN(+) patients compared with controls. PG(+) was associated with anti-nuclear cytoplasmic antibody seropositivity (P = 0.03) and higher anti-nuclear cytoplasmic antibody level (P = 0.02) in Crohn's disease.

Genetic associations with PG included known IBD loci (IL8RA [P = 0.00003] and PRDM1 [0.03]) as well as with USP15 (4.8 × 10−6) and TIMP3 (5.6 ×10−7). Genetic associations with EN included known IBD susceptibility genes (PTGER4 [P = 8.8 × 10−4], ITGAL [0.03]) as well as SOCS5 (9.64 × 10−6), CD207 (3.14 × 10−6), ITGB3 (7.56 × 10−6), and rs6828740 (4q26) (P < 5.0 × 10−8).

Multivariable models using clinical, serologic, and genetic parameters predicted PG (area under the curve = 0.8) and EN (area under the curve = 0.97).

Cutaneous manifestations in IBD are associated with distinctive genetic characteristics and with the similar clinical characteristics, including the development of other extra-intestinal manifestations suggesting shared and distinct etiologies.

In addition to gastrointestinal tract pathology, the inflammatory bowel diseases are associated with extra-intestinal manifestations (EIMs), including cutaneous EIMs such as pyoderma gangrenosum (PG) and erythema nodosum (EN). Although troublesome in their own right, EIMs may “tag” more homogenous subgroups within IBD with unique pathogenic characteristics.

PG, observed in 0.5% to 5% of IBD patients, is reportedly more commonly associated with colonic disease and is a significant source of morbidity requiring intensive, in-patient multidisciplinary approaches to management.

1,–6 PG is a neutrophilic dermatosis and usually begins as a papule or pustule at a site of trauma with a surrounding violacious, undermined border.

7 PG can significantly affect activities of daily living, quality of life, and can be cosmetically disfiguring leading to permanent scarring, significant pain, bacterial superinfection, and may require skin grafting.

7,8 Moreover, potent immunosuppression with therapeutic agents, such as intravenous cyclosporine or infliximab, may be needed.9,10 There are limited data on genetic associations with PG, although small studies have suggested association with PSTPIP1, PTPN6, and TRAF3IP2.11,–13

EN is the most common dermatologic manifestation in IBD and affects 3% to 15% of IBD patients.

14,–16 Typically diagnosed clinically and rarely before the onset of IBD, lesions most commonly affect the anterior surface of the lower extremities in the form of tender, erythematous, and raised nodules with histology revealing a neutrophilic inflammatory infiltrate and panniculitis.

6,17,–20 Previous studies have noted that EN is also associated with colonic disease and with a more benign IBD natural history.1,15 Previous studies have suggested an association between the HLA and EN in IBD.13,21

As researchers begin to understand the molecular characteristics of IBD, there is a need to better characterize subgroups of these complex and heterogeneous conditions.

An increased understanding of the etiology of both PG and EN in IBD may highlight potential novel therapeutic pathways for the subset of patients who are at risk for skin manifestations.

The aim of this study was to better characterize IBD disease behavior, serologic profiles, and genetic associations among patients with PG or EN.


We reviewed 2 large IBD databases for cases of PG and EN. The Cedars-Sinai Medical Center (CSMC) IBD Research Repository contains clinical (demographics, disease phenotype, disease history, EIMs, treatment records), serologic, and genetic data on more than 5000 consented IBD patients followed up at our center.

From this database, we identified all subjects with genome-wide association (GWA) genotyping for inclusion in this study.22,23 Those subjects with at least 1 documented episode of PG [PG(+)] or EN [EN(+)] were identified and underwent a detailed confirmatory medical record review.

Subjects without a history of PG [PG(−)]or EN [EN(−)] formed the control group.

An episode of PG was confirmed on record review either dermatology consultant impression or typical features, as defined elsewhere as having 3 or more of the following: (1) leg or peristomal location, (2) pathergy, (3) initial pustular lesion, (4) purulent discharge, (5) violacious or undermined borders, and (6) crater- holes/cribiform scarring.24 Histology was reviewed, when available, to exclude alternative diagnoses. An episode of EN was confirmed via chart review by dermatology consultation or typical features, including erythematous, nonulcerative, raised, tender bruise- lesions usually on the legs.

We also included IBD cases with GWA data available from the National Institute for Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium (NIDDK-IBDGC), Cedars-Sinai Medical Center, Johns Hopkins University, University of Montreal, University of Pittsburgh, University of Toronto, Yale University, and University of Chicago (Data Coordinating Center).

The validity and reliability of the clinical features collected in this database has been previously documented.25 The clinical and genetic data on IBD patients (care was taken to exclude any CSMC patients in the NIDDK cohort to avoid double “reporting”) were combined with the samples from the CSMC database (see Fig., Supplemental Digital Content 1, http://links.lww.

com/IBD/A392). The serologic analysis was limited to the subjects identified in the CSMC IBD Research Repository. The CSMC IBD Research Repository contained 4137 IBD subjects with GWA data. Of these, 64 were PG(+), 55 EN(+), and 4073 PG/EN(−). The NIDDK-IBDGC database contained 1619 IBD subjects with GWA data (28 PG(+), 48(EN+), and 1591 PG/EN(−)).

The genetic and clinical analyses were performed on the combined datasets. Therefore, this analysis consisted of 5756 subjects (92 PG(+), 103 EN(+), and 5664 PG/EN(−)). The serologic analysis was limited to the subjects in the CSMC IBD Research Repository (total 4137 subjects: 64 PG(+), 55 EN(+); and 4073 PG/EN(−)).

A total of 14 patients with both EN and PG were identified and were included in both EN and PG analyses.

Clinical and Serologic Phenotyping

Clinical data were collected at all contributing centers by chart review and included patient demographics (age, gender, ethnicity, race), family history, disease duration, disease phenotype (IBD subtype and disease location/behavior according to the Montreal Classification), surgical history, treatment record, smoking status, and presence or absence of other EIMs.26 IBD-associated serologies (anti–Saccharomyces cerevisiae antibodies [ASCA IgG and IgA], perinuclear anti-nuclear cytoplasmic antibody (pANCA), anti-flagellin [anti-CBir1], anti–outer membrane porin C [anti-OmpC], and anti–Pseudomonas fluorescens–associated sequence I2 [anti-I2]) were measured by enzyme-linked immunosorbent assay, as previously described.27 Antibody levels were determined and results expressed as enzyme-linked immunosorbent assay units/milliliter (EU/mL) that are relative to CSMC laboratory (IgA-I2, IgA-OmpC) or a Prometheus Laboratory standard (SanDiego, CA; IgA and IgG ASCA) having been derived from a pool of patient sera with well-characterized disease found to have reactivity to these antigens. Quantitation of IgG anti-CBir1 reactivity was expressed in enzyme-linked immunosorbent assay units derived a proportion of reactivity relative to a standardized positive control. Quantitative serologic results were converted to binary variables (i.e., positive or negative). Qualitative positivity to any antibody was defined as being greater than cut-off values 2 SDs above mean control titers for each assay. All assays were performed blind to any knowledge of patient clinical characteristics.

Genotyping and Genotype Quality Control

Genotyping was performed at Cedars Sinai Medical Center using Illumina Human610 platforms for Crohn's disease (CD) and HumanCNV370 platforms for ulcerative colitis (UC).21,22 The NIDDK-IBDGC samples were genotyped using the HumanHap300 and HumanHap550 platforms as previously described.

28,29 In the genotyped datasets, individual and genotype missingness, allele frequencies, and deviations from Hardy–Weinberg equilibrium were calculated using the PLINK software package (∼purcell/plink).

Of the 5756 IBD cases, 21 failed quality control metrics, in which we required a genotyping call rate of >95%, inbreeding coefficient of