All About Erythema Nodosum

One patient's quest to gather the world's knowledge about Erythema Nodosum (EN).

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Stereographic skin clinic card about erythema nodosum 

The bottom right-hand text reads “Copyright 1910, Dr. S.I. Rainforth, N.Y.” 

From the Laupus Health Sciences History Collection at East Carolina. See a high-resolution photo in the ECU Digital Library. 

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“Treatments” page update

I just added sources for all of the treatment options on the “Treatment” page. Now all of the suggested treatments have links to medical journal articles describing how they were dosed and used, and more about the situation in which they worked. 

The sources are all small studies or cases. There are no double-blind studies testing the efficacy of any of these drugs on idiopathic EN. 

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EN News: February, 2017

What erythema nodosum research was published this month?

It has been a busy year so far in erythema nodosum research. January brought us some interesting insights into EN and IgA deficiency. In February, researchers saw EN in several studies about other illnesses, found a successful treatment for EN and idiopathic mastitis, and asked some interesting questions about granulomas.  

These articles were all indexed by Google Scholar in the month of February and have publication dates in January, February, or March. Most of these articles are behind a paywall, but if you are interested in one of them, I can help you find somewhere to read it.

Studies:

Coexistence of idiopathic granulomatous mastitis and erythema nodosum: successful treatment with corticosteroids Eleven patients who had both erythema nodosum and idiopathic granulomatous mastitis (IGM) were treated with methylprednisolone. The erythema nodosum was completely gone from all of the patients within two weeks of starting the medicine. Within twelve weeks, the IGM symptoms were also gone from all of the patients. The researchers kept up with all of the patient for sixty months: neither condition came back.

HTLV-1 seroprevalance in sarcoidosis. A clinical and laboratory study in northeast of Iran 125 sarcoidosis patients in northeast Iran were tested for a virus that is known to dysregulate the immune system. 76 of those patients had erythema nodosum (63.2%). If I am reading their tables correctly, only two of those patients were positive for the virus. In the end, the study did not see the virus more in sarcoidosis patients than was normal for the area.

New insights on tuberculous aortitis Tuberculosis infections in the aorta are very rare. This study compared eleven patients with tuberculosis aoritis, three of whom had erythema nodosum.

The effect of vitamin D on clinical manifestations and activity of Behçet’s disease In this study, 68 patients with Behçet’s disease had their vitamin D levels tested. The authors wanted to know if treating Behçet’s patients with vitamin D would help with their symptoms. The vitamin D didn’t seem to help. Four of the 68 patients had erythema nodosum. Their vitamin D levels were lower than in Behçet’s patients without EN, but there were not enough patients to determine anything.

Association between rheumatic diseases and cancer: results from a clinical practice cohort study 1750 patient records from an Italian rheumatology clinic were analyzed for a connection between autoimmune diseases and cancer. Erythema nodosum was not studied on its own, but instead was part of a group called “isolated immunologic manifestations.” This group was not discussed much in the article; out of the 112 patients in the “IMM” group, only 3 got cancer within two years. The article does not mention specifically how many EN cases were included.

Evaluation of asymptomatic venous disease by Doppler ultrasonography in Behçet’s disease patients 22 patients with Behçet’s disease and 22 controls were tested for vein disease. Eleven (50%) of the BD patients had EN.

Individual Cases:

A granulomatous conundrum: Concurrent necrobiosis lipoidica, cutaneous sarcoidosis and erythema nodosum in a nondiabetic patient This very interesting case from Australia describes a woman with three different skin conditions on her shins at the same time: necrobiosis lipidica, cutaneous sarcoidosis, and EN. All three appeared at different times and responded differently to treatments, but the authors wonder if they were all related since all three were granulomatous. (Granulomas are collections of immune cells; they are basically your body’s way of trying to wall off foreign substances.) There is still a lot we don’t know about the way granulomatous disorders work, and as far as the authors (or I) can tell, this is the first time all three of these conditions have happened concurrently.

Pulmonary Sarcoidosis in Behçet's Disease Treated with Adalimumab In this case, a man had Behçet’s disease that wasn’t responding to treatment. His doctors put him on adalimumab, an anti-TNF agent which suppresses the immune system, and he quickly got better. Six months later, he went back to the doctor because of night fevers, muscle pain, and joint swelling. A few days later his chest started to hurt, and he had erythema nodosum on both legs, among other symptoms. He tested positive for the Legionella pneumophila bacteria, and he was diagnosed with Legionnaire’s disease. But, after treatment for the Legionnaire’s, they discovered that he also had sarcoidosis of the lungs. Both Legionnaire’s and the sarcoidosis are potential side effects of anti-TNF drugs, and they both are associated with erythema nodosum, although sarcoidosis is much more common.

Image challenge: Painful leg lesions in a young woman This “pop quiz” style case study has a photo of an unusual presentation of hormone-related EN. The spots are around both of the patient’s knees and a large, dark red patch is around her left ankle. The skin appears to be splitting around the ankle as well, although it’s hard to tell from the photo.

Fever and arthralgia after ‘volcano boarding’ in Nicaragua A man and a woman both contracted histoplasmosis after a trip to Nicaragua; the woman developed erythema nodosum. The authors of the article blame “volcano boarding,” despite not finding the fungus that causes histoplasmosis in a sand sample.

Adverse reactions to fluoroquinolones in the Nigerian population: an audit of reports submitted to the National Pharmacovigilance Centre from 2004 to 2016 A Nigerian patient taking Levofloxacin developed erythema nodosum, likely as a drug reaction. This reminded me of a case from 2012 when a kidney transplant patient was treated for pneumonia.

A randomized, double-blind trial of abatacept (CTLA4-ig) for the treatment of takayasu's arteritis One patient in this double-blind trial of a drug for takayasu’s arteritis had erythema nodosum during a relapse of their disease. Takayasu’s arteritis is a rare disease that damages the arteries around the heart.

Books and Review Articles:

Dermatopathology 101: Part 1 – Inflammatory skin diseases Three German doctors published an article about diagnosing different inflammatory skin diseases under a microscope and included a section about erythema nodosum. The biopsy slides they included are clear, straightforward examples of the microscopic features of EN.

Misdiagnoses and Mimics:

A clinicoepidemiologicalstudy of cutaneous tuberculosis in a tertiary care teaching hospital in Andhra Pradesh, India In this article, a case of erythema induratum was originally diagnosed as erythema nodosum.

I am interested in reading this article, but I don’t have access to it:

Lee, Jonathan J. (02/01/2017). "Cutaneous Reactions to Targeted Therapy". The American journal of dermatopathology (0193-1091), 39 (2), p. 67.

This post was an experiment. Would you like to see monthly research round-ups on this blog? Let me know! 

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Hi, I'm a 19 year old girl from Belgium with EN and it stands out that EN appears in moments that I'm very tired and stressed. Could that be a "trigger"?

Hello! Thank you for the question. As far as I know, there hasn’t been a study about stress triggering EN specifically, but since EN is an autoimmune disease, it would not be surprising. There is a lot that we don’t know about how exactly stress, inflammation, and autoimmunity are related, but they definitely are. 

There is a very comprehensive article about stress and autoimmune diseases called Stress as a Trigger of Autoimmune Disease by Ljudmila Stojanovich and Dragomir Marisavljevich. It’s not available for free online, but I got a copy from my university library; I can email it to you if you are interested. According to the article, when we get stressed, our bodies produce hormones, and “repeated episodes of psychological stress” can change how our immune systems are regulated, leading to weak immune systems or autoimmune diseases. Flares of rheumatoid arthritis and Crohn’s disease are both associated with stress, for example. (And flares of EN are often seen at the same time as flares of other autoimmune diseases, like Behçet’s.) 

When I last spoke to her, Rebecca Strecker, a woman who has been doing EN patient advocacy work for more than a decade, told me that stress is one of the most common lifestyle triggers other patients tell her about. (And she runs an online support group with over 3,000 members.)

I suggest getting an appointment with a doctor (especially a dermatologist or rheumatologist) if you have chronic EN and don’t know the cause. Some very serious illnesses (like Behçet’s, sarcoidosis, or in your area, Yersinia infections) can cause EN and you should get a professional opinion if you haven’t already.

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Telemedicine and Rare Disease Registries: Interview with Dr. Rodolfo Valdez of the US CDC

I recently read two very interesting articles about public health and rare diseases, and realized that one author, Dr. Rodolfo Valdez of the CDC, had helped write both of them. I reached out to him last month and asked him some questions about what the future might hold for rare disease advocacy and research. 

In case you are curious, the articles were: 

The need for a next-generation public health response to rare diseases

Public Health and Rare Diseases: Oxymoron No More 

There is a list of terms and definitions at the end of the interview. 

You have written a few articles recently about public health and rare diseases. What inspired you to start researching that area?

I was working in CDC’s Office of Public Health Genomics and was offered the opportunity to move to the Rare Disorders and Health Outcomes team where I could help with establishing public health research projects for three diseases: muscular dystrophy, spina bifida, and fragile X syndrome. I accepted the offer and now I am totally dedicated to the epidemiology of rare diseases.

You’re an epidemiologist, so my first science question is about epidemiology. What is the most useful way of tracking the incidence and prevalence of rare diseases? How useful is an incidence or prevalence statistic that is calculated based on small numbers of cases in a population?  

For example, this blog is about erythema nodosum, which has an estimated prevalence of 1-5 per 100,000 people in the United States. But that is only an estimate, based on studies of fewer than 100 cases. Is that normal for rare disease research? If not, what does a good epidemiological study of a rare disease look like? 

Incidence and prevalence are not easily measured for rare diseases. A major difficulty is that these two measures are calculated using the size of the population, and for these diseases this size is usually unknown or unknowable. These are however important measures ...

... and a good epidemiologic study must attempt to estimate the presence of a disease in a population. Currently the best approach to study the epidemiology of rare diseases is through patient registries. Registries give an indication of the overall impact that a given disease has on a population. Another approach becoming more popular through the digitization of health care data is using very large datasets to find cases of rare diseases. This approach is limited to diseases that currently have a diagnosis code, and currently and most rare diseases don’t have a code. The epidemiology of rare diseases is still a work in progress. Hopefully, with recent advances in statistics and computer science this progress will accelerate.

In your paper, you suggest registries for patients with rare diseases. What would a patient registry look like, and what would it be used for? Who would run it?

The best way to collect health information from a population is through surveys. Ideally surveys collect information from a random sample that is large enough to make the results applicable to the entire population. Another way is through surveillance, where an entire population is continuously monitored to collect health-related information on a single condition or a group of closely related conditions. Unfortunately, these approaches are largely impractical for rare diseases.

The small number of cases and the scattered distribution of patients with rare diseases makes the sampling or monitoring of their populations difficult. The most common alternative is to build registries. A rare disease registry, in a sense, is an artificial population extracted from a real community of patients with a rare disease. Patients are identified in the places they regularly attend (clinics, or patient organization websites for example) and they are invited to provide information regularly to the registry. Virtually any institution or person can organize a registry and registry vary from simple to complex according to their objectives; however, it is extremely important that the organizers of the registry carefully plan the information they need to collect, how they plan to collect it, and for how long they are going to collect it.

Anyone interested in creating a registry should first consult experts with a background in developing data collection tools, including experts in the ethics of research participation.  

The rigor in data collection is crucial because well-collected registry data may be used to evaluate treatments and outcomes, exposure to risk factors, cost of care, satisfaction with care, effects of policy changes, quality of care, etc.

You mentioned telemedicine as a way for patients with rare diseases to access proper care no matter where they live. How would this work in the United States, when health insurance is so regional?

Telemedicine is not a new idea but now it looks more feasible than ever with the abundance of high-resolution cameras and monitors, the widespread availability of high-speed Internet, and the nearly universal use of smartphones.  There are barriers though: many legal and regulatory changes must take place before doctors can see and treat patients across state and even across county lines. Liability, licensing, and reimbursement, for example, must be considered.

Hopefully, the many advantages of telemedicine would prevail; among them, we can cite: convenience, expanded access, and potentially reduced health care costs. Of course, before recommending its widespread use, telemedicine must be thoroughly evaluated. These advantages are only assumptions. We know little about the actual costs and savings associated with telemedicine and we need objective information on the medical fields where telemedicine can improve health outcomes. Given the wide geographic spread of patients with rare diseases, the management and treatment of these diseases are good candidates for telemedicine.

What steps can be taken to clarify and define ICD codes for rare diseases? ICD 11 is in beta right now and open for comments. Is that a good way for patient advocacy groups to get involved in the process?

ICD codes provide a standard way of reporting and monitoring diseases across hospitals, regions, and countries, and over time. These codes are developed by a committee at the World Health Organization. This is the Frequently Asked Questions section of the organization’s website, which includes information on how to participate:

http://www.who.int/classifications/icd/revision/icd11faq/en/

More specific to rare diseases is the fact that the international consortium Orphanet has developed a comprehensive list of codes for rare diseases (Orpha codes). This coding system can be linked to ICD codes. An adaptation of this coding system was recently used in an Australian study with impressive results: 45,213 living cases of rare diseases identified in one state just by using administrative datasets (Article link: Genetics in Medicine). The codes developed by Orphanet are highly regarded and now form the basis for including rare diseases in ICD-11. 

Definitions:

Rare disease: in the USA, if fewer than 200,000 people have a disease, it is officially a rare disease. That means rare diseases occur in fewer than 1 in 1,600 people. Other countries use different definitions, but they are all around 1 in 2,000.

Epidemiology: the study of the occurrence, distribution, and control of diseases in populations.

Public health: the science of promoting and protecting the health of a population.  

International Classification of Diseases: a standardized classification system for diseases and injuries. Each has a unique identifier is called an ICD code. It is maintained by the World Health organization, and updated every ten years or so. They are used by researchers, health systems, and governments to keep track of health information.

Dr. Valdez was kind enough to send along his definitions of incidence and prevalence.

“Prevalence and incidence are two basic concepts in epidemiology. They are useful because a simple count of the number of cases in a population is not very informative. For example, 250 cases of a disease in a population says little if we don’t know the size of the population. The reaction is different if the size is one thousand or ten thousand. Prevalence takes the size of the population into account. In this example, the prevalence is 0.25 or 25% in the population of one thousand individuals (250/1,000) and 0.025 or 2.5% in the population of ten thousand individuals (250/10,000).

It is important to highlight that prevalence is a snapshot of a disease in a population. It is even more informative if the period in which it was calculated is included when reporting the number. For example, the prevalence of a disease was 25% in 2015 in a population of one thousand individuals.

Incidence is related to the number of people developing a disease in a given period. More specifically, it is the proportion of new cases in a population in a given period. For example, if we calculate in 2016 the prevalence of the same disease in the same population of the previous paragraph and we now count 280 cases (let’s assume no migration or deaths for simplicity), then the incidence is 30 new cases (280 – 250) in one year for a population of one thousand or 30/1,000 = 0.03 or 3% per year. That is, the number of affected has increased by 3% in a year.”

Dr. Rodolfo Valdez is an epidemiologist with the Rare Disorders and Health Outcomes team, part of the National Center on Birth Defects and Developmental Disabilities at the Centers for Disease Control and Prevention (CDC). Working with CDC scientists and external investigators, Dr. Valdez helps in the planning and execution of research projects related to public health aspects of three rare disorders: muscular dystrophy, spina bifida, and fragile X syndrome.

He has a Bachelor’s degree in human population biology from Simón Bolívar University in Venezuela, a Masters of Science in human genetics from the Venezuelan Institute for Scientific Research, and a PhD in Physical Anthropology from Pennsylvania State University.

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Translators

Thank you to people who have already written in volunteering to help translate! I will post a longer volunteer call-out once I know exactly what languages I need the most help with. Feel free to write me a message with what language you speak and your contact information, and I will be in touch with you early next year. 

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Hello readers! Here is my December research update. 

I am still hard at work finding, tagging, and cataloging historical literature about EN for the Erythema Nodosum Library project, a growing database of old medical journal articles, textbooks, manuscripts, and government proceedings. Current total: 834 documents, many of them case studies. 

I have been so focused on my work the last few weeks that I haven’t written a post in a while. But don’t worry, I have some very cool posts planned for the near future: 

• A nice woman from Leeds answered the Craigslist ad and I now have a PDF of George Frederick Walker’s thesis from 1924. It contains what might be the earliest surviving photograph of erythema nodosum, which I am excited to share with you. 

• I am interviewing Dr. Rodolfo Valdez from the CDC about his work in rare diseases and epidemiology. He has lots of great ideas about how medical institutions should support people with rare diseases. 

• I found and scanned another last-paper-copy thesis, also from the early 1920′s, by a German endocrinologist who worked with Magnus Hirschfeld for many years. 

• Are you bilingual? I would love your help with unofficial translations. If my goal is to collect everything that modern science knows about EN, I will need people who can help me sort through articles in languages I don’t know, like Portuguese, Spanish, German, Polish, and Japanese. I also want to have some important English articles about EN summarized in other languages.

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Looking for a very old thesis

Hello! I am a university student from North Carolina State University in the US. I am doing a literature review of a disease called erythema nodosum, not for my studies but because I actually have...

Here is an online ad I placed on the Leeds craigslist to see if anyone who lived near the University of Leeds would be willing to help me learn more about an old medical school thesis from 1924. Of course, I offered to pay them. 

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Life with Chronic EN

What does life look like for someone with severe, chronic* erythema nodosum? 

Erythema nodosum is generally considered a painful but minor health problem. Most of the time, it clears up on its own with a few weeks of rest. But in a small number of cases, erythema nodosum can become chronic. Often, patients with chronic EN have other chronic illnesses, like inflammatory bowel disease or rheumatoid arthritis, and the symptoms for both diseases flare at the same time, however some chronic EN patients have no other health problems. 

Although it never threatens the internal organs and only rarely leaves a scar, chronic erythema nodosum can be debilitating. I asked the members of a Facebook support group for EN patients to describe their experiences with chronic EN, and below are some of the responses (published with permission). Some describe mobility issues, others talk about uninformed doctors and friends. Many describe the isolation that comes with having a rare disease; several moms have to tell their children not to hug them. 

It’s important to remember that most erythema nodosum, even chronic erythema nodosum, does not usually get this bad. I have gotten to know some of these people over the last year, and many of them do not have access to adequate treatment for their disease. In contrast, my chronic EN is annoying, but well-managed. 

If you have chronic erythema nodosum and it is affecting your quality of life, you are not alone. Thanks to all of the people who sent in testimonials: if you would like me to add your story, write me here. 

Chronic erythema nodosum, described by patients: 

"It depresses me that I cannot even walk without pain or do simple everyday tasks anymore. I have to pick my leg up to get in and out of my car. I constantly apologize to family and friends because I miss events, and they have to watch me struggle just getting around the house. Seeing the toll it takes on my husband to watch me barely make it up the stairs.... that hurts just as much as the pain in my legs." -Ashlyn K.

"I don't want to sit in front of a doctor reading from the Internet. I want a doctor that will refer me to a specialist. My legs and feet are swollen and it's a drain on my energy levels. It makes me feel like a lazy old lady. I'm 44." -Natasha C. 

"I hate not being able to walk or stand up. Relying on crutches to get around flare ups that last years, not 6 weeks like doctors say they will. Not being able to run around the park with my children. Hoovering the floor and having to sit down for a rest. Not being able to hug my children because the pain is unbearable and I get the EN nodules all over my body. I get a flare up when I knock myself instead of a bruise, so I am afraid to do normal things." -Poppy P. 

"I'm having a chat with a friend as I type this, a friend who insisting on visiting for a coffee and a chat AFTER I explained how unwell I am and that I am not up to visitors. Now I'm feeling guilty and yes, a little angry at their insistence. When my EN flares with my other autoimmune conditions, just managing basic essential things like showering and toileting is hard enough. Having to deal with visitors and feeling the need to entertain them is way too much to take on board. What's even harder is restraining your frustration and temper when expectations are put on you during you bad times." -Trudi B.

"I remember a New Year’s party when I was 18 years old. I couldn't walk from one street to another without being in agony, and I got so upset over it and my swollen legs that I sat alone and cried. I was 18 years old, I should have been partying with everyone else!" -Caroline R. 

"My erythema nodosum experience: telling hubby not to hold my hand because my wrist is the joint of the day that is flared up. Explaining to people in restaurants why it's hard to stand because my knees flare. Yelling at my pugs because they love me and rub against my extremely painful lower legs. I turn into (forgive the wording) a Super Bitch. I can't sleep long and I can't stay awake when I want. Whenever I see a 99.3 on my thermometer I get sick to my stomach because I know what's coming. I can't plan anything because every 6 to 8 weeks I’ll be in bad shape once again for who knows how long." -Melanie L. 

"My chronic EN is oppressive, it can crush my spirit, and it can make me depressed. I suffer severely with joint pain and stiffness whenever I have colitis issues, sinusitis, or seasonal allergies. I've had EN flares (that can go on for up to two years at a time) since a bout of strep in 1989. It even struck me during my honeymoon from the stress of the wedding and planning." -Jacquie, founder of the EN Facebook group

"As a very active mother, grandmother and outdoorsy person, my life has changed tremendously since I first got EN, and it has only gotten worse since becoming chronic. It hurts to walk, it hurts to move and it hurts to pick up and hold my grandkids. I feel horrible all over most of the time now, and I have to spend a lot of time "resting" in bed. I have a Harley that sits in our garage now, and I haven't gotten on a bike since my first EN flare up four years ago, after having ridden a bike for 40+ years. I've become that person I swore I never would, one that hobbles, hurts and feels like I complain too much about how miserable I am. Thankfully I have a supporting family who sees and understands my pain and frustration. I get rid of the EN, and lo and behold, it's right back again. A true life changer for our family. I'm sick of being sick!" -Jill W.  

"My EN experience is just pain. It's like having been hit with a baseball bat in the shins over and over. The hobbling, the needing help up the stairs, the aching deep within your joints and the purple hideous lumps. I have a 4-year old, a 3-year old, and a 6 month old, and I have to tell them not to touch me because I squeal from the sensation." –Sky 

"As a mum of three young girls, I find the fatigue, nodule pain and joint pain the most difficult. All I want to do is play with my babies, but I'm stuck sitting in a chair, sore and frustrated." -Emma B. 

"I'm sick and tired of being sick and tired. And I'm so tired of dealing with pain every day. I can't do the things I used to and I feel like I let my family down because of this. -Kristen M. 

"As I read everyone's comments, I find myself in tears, and I realize I am not alone. In 20 years I had never met anyone else with EN, and then I found this group. The constant physical and emotional pain is draining. It's hard hearing "You're so young to be limping around!" and "You're always sick! But you don't look sick." I wear jeans in the summer, because people stare, and trying to explain a condition people don't understand is frustrating. But then you can't have anything touch your skin so you just stay home. As I get older my flare ups have gotten worse, and so has all that goes with it. Most people wouldn't understand the excitement of seeing bruises form on my legs, but that means my flare-up is coming to an end. But these days, bruises form and new nodules begin; it's never ending. I try to remind myself to not pity myself, and that it could be worse, but some days it's hard to put that smile on my face and be there for everyone else. I am just so glad I found this group; now I don't feel so alone in my EN struggles." -Bonnie M.

* There is some disagreement about how to classify the different variants of erythema nodosum, and researchers have named many sub-types (some of which you can read about on our Types page). Chronic erythema nodosum cases generally fall into two categories: either new nodules form every once in a while and the condition never seems to go away entirely, or they come in big flares, then heal up, then flare again. The first type, which is what I have, is what medical researchers mean when they say “chronic erythema nodosum” – and it tends to be less debilitating. The second type would probably be called a chronic case of classical erythema nodosum… but that’s a mouthful. 

In any case, they are both considered to be erythema nodosum, and they last for a long time. That’s what I mean when I say “chronic erythema nodosum.” 

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Research Update: The library found a very interesting book for me this week. It was a collection of medical journals from 1913. The articles about EN were interesting, but I also liked the vintage illustrations. 

Because the book was so old and fragile, I couldn’t take it out of the library. I had to scan the articles I needed. 

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Updated trigger list

I have updated the “Triggers” page of this website to list many documented triggers I have found in medical literature. They’re organized into three parts: 

very common triggers

uncommon but well documented triggers 

triggers that aren’t well documented 

My next step will be to find online links for all of these case studies so that anyone can read about them. 

For the most current list, visit enodosum.com/triggers. 

Below are all of the conditions very commonly associated with erythema nodosum according to peer-reviewed medical literature:

Streptococcal infections (like strep throat)

Sarcoidosis

Tuberculosis (TB)

Inflammatory bowel diseases (like Crohn’s or Ulcerative Collitis)

Taking oral contraceptives

Taking some antibiotics

Yersinia  

Behcet's disease

Tularemia

Pregnancy

Cancer (especially lymphoma and leukemia)

Coccidioidomycosis (Valley fever)

Below are conditions represented by a small collection of case studies:

Granulomatis mastitis

Brucellosis

Bartonella (Cat-scratch disease)

Chlamydia

Histoplasmosis

Kerion celsei or tinea capitis

Salmonella

Acne fulminans

Tularemia

Lupus

Takayasu arteritis

Hepatitis B & C and Hep B vaccine

Sweet's syndrome (usually also reactive)

Below are conditions which are represented by single case studies, unofficially associated with erythema nodosum, or informally reported to me by other patients. I may move items to the top list if I find more information:

Mononucleosis (Mono)

Allergy to the Orf virus

HIV

Campylobacter

Coccidioides immitis

B. burgdoferi

Blastomycosis

Lymphogranuloma venereum

Leptospirosis

Milker's Nodules (Parapox)

Mima-Herellea

Syphilis

Mycoplasma

Pasteurella pseudotuberculosis

Psittacosis

Antiphospholipid antibody syndrome

Blastomycosis  

Chlamydophila pneumenae

Shigella

Toxoplasmosis

Myelodysplastic syndrome

Nodular cystic fat necrosis

H. cinaedi

H. Pylori

Q fever (Coxiella)

Ringworm

Lyme disease

Bronchitis

Bronchiolitis

Giardia

BRAF-inhibitor therapy

Acupuncture reaction

Allergy to tattoo ink

Jellyfish stings

Pigmentary epitheliopathy

References coming soon. Most cases are indexed in the NCBI database: https://www.ncbi.nlm.nih.gov/

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Ornate “Ex Libris” stamps and bookplates from old medical textbooks 

I am now one century into my literature review! I have collected the full text (or at least abstract) of basically every english-language article and book written about erythema nodosum before January 1, 1900. 

Most modern medical discoveries are published in research journals well before finding their way into books, but it hasn’t always been that way. Between 1809, when Willan first described the disease, and 1900, the majority of the discussions of erythema nodosum were in long books. 

While looking through these old books, I couldn’t help noticing all of the beautiful bookplates and library stamps from various science libraries around the world. The photos above are my favorite examples. Sometimes the inscriptions tell stories about who donated the book; about when, and why, it changed hands. 

Most of these old books were digitized by the Google Library project; you can tell by the watermark below each page. By marking the digital copies of these texts, Google is continuing a long tradition of tagging the works passing through their “library.” 

Eventually I would like to share the data I’m collecting with any researcher or patient who needs it. Maybe I should get a stamp of my own! 

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What does EM mean?

In medical texts, abbreviations can get very complicated. The abbreviation for erythema nodosum is EN. Sometimes in medical texts, writers might use the abbreviation EN and EM together. This can get confusing. There are three things that EM might mean in context of erythema nodosum. 

Erythema Multiforme Another rash in the “erythema” family is erythema multiforme, or EM. If you see the letters EM in a medical text about rare skin issues, they might be talking about erythema multiforme. The two diseases share some triggers, but they look different and occur on different parts of the body. Very rarely, patients have had both at the same time. 

Extraintestinal Manifestations Erythema nodosum is a common symptom of bowel diseases like ulcerative colitis and Crohn’s disease. They can have symptoms in the intestines, or outside of the intestines. Symptoms that appear in the intestines are called intestinal manifestations, while symptoms that appear in other parts of the body like the eyes or skin are called extraintestinal manifestations, or EM for short. 

Erythema Migrans This is where it gets very complicated. Erythema migrans (EM) can mean two things. Most commonly, it is the shortened version of erythema chronicum migrans, the “bull’s eye” rash that appears around an infected tick bite. Erythema chronicum migrans is often the first symptom of Lyme disease. 

A completely separate disease called stomatitis erythema migrans, or oral erythema migrans, is a harmless tongue condition, and has nothing to do with lyme disease. It is occasionally abbreviated as EM. I doubt it would be mentioned in a text on erythema nodosum. 

Erythema nodosum migrans, the variant of erythema nodosum that includes “central clearing,” is never abbreviated as EM. Instead, people shorten it to ENM. 

References:  Medscape - Erythema Multiforme Medicina Clinica - Extraintestinal manifestations in inflammatory bowel disease Wikipedia - Erythema chronicum migrans  JAAD - An unusual presentation of Vilanova disease 

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Are there EN support groups?

Yes. I found three erythema nodosum-specific support groups online, as well as forums for people who have EN because of other chronic diseases. Below are some links to active groups and forums online: 

Erythema Nodosum Support Group Active since 2003, this group is by far the oldest and largest. Founded initially because the moderator of another EN group used their platform to advertise shark oil, this Yahoo group has amassed hundreds of volunteered patient case studies and rare triggers. Membership requires a Yahoo account and an application. 

Erythema Nodosum (EN) Facebook group  Although not quite as old as the Yahoo group, many people find Facebook much easier to use, and this group is very active. Other patients are quick to comment supportive messages and post helpful, if occasionally unsound, advice. 

For People Who Have Erythema Nodosum  Here is another Facebook group, although it may not be active anymore.  Looking for a trigger-specific forum? 

If you have Crohn’s or other kinds of IBD, there are many threads about EN at crohnsforum.com. Healing Well has several disease-specific forum threads: Lyme and EN, Crohn’s and EN, and Rheumatoid Arthritis and EN 

There is a forum for people who have EN and fibromyalgia. If you are pregnant and looking to connect with other moms, you might like EN and Pregnancy at NetMums. There even a forum for dealing with EN when you love to run over at Runner’s World: Erythema Nodosum for runners 

Remember: anyone can post in these groups. Some of the advice given on these websites is completely unscientific, and might even be dangerous. Talk to a doctor before trying strange supplements you found online. 

And let me know if you want your group to be added to this list. 

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Does Erythema Nodosum Only Appear on the Shin Bone?

What parts of the body can erythema nodosum cover?  

When I first showed up at a student health clinic with swollen ankles and painful splotches covering both legs, the doctors there considered erythema nodosum, but then decided against it, since I had nodules not only on my shins but on my feet and calves. They weren’t sure about it, but they thought erythema nodosum only occurred on hard, bony areas. 

Good thing they asked for a dermatologist’s opinion! It’s a common misconception, but erythema nodosum can sometimes appear on soft parts of your body. While it does seem to crop up more on shins, ankles, and elbows, it has also been seen on calves, thighs, and feet. A few articles have described it as appearing on the trunk, or even on the neck and face. 

Medical definitions usually mention a tendency for nodules to appear over the shin bones, but erythema nodosum is not exclusive to that area. 

Even in 1905 doctors had figured this out.  In his book Nodal Fever, Dr. Alfred Lendon wrote: 

“The extensor aspects of the limbs are undoubtedly more favourite sites for the nodes than the flexor, but the relationship of the nodes to the subcutaneous bony surfaces has, I think, been too strongly insisted upon; they are in no sense, of course, periosteal lesions, and I have pointed out many a time nodes seated on the outer aspects of the legs, quite free of the edges of the tibiae.” 

Basically, while they are more common on the shin side of the leg, they don’t need to grow on bones. 

That is where this question could have stopped. Yes, EN nodules can spread to soft tissues. But in researching this question, I came across a mystery. 

The famous German dermatologist Dr. Otto Braun-Falco wrote the following passage in a popular medical textbook: 

“While erythema nodosum can appear above the knees and even on the arms, such a pattern should raise the question of other types of panniculitis.” (For example, the look-alikes discussed here.) 

So why are definitions these days so much broader? Why do some peer-reviewed journal articles list the neck and face as sites for EN nodules?

In fact, I have not been able to find a case of erythema nodosum appearing on the trunk or face since the 1970s. Even in the 1998 study by Bernard Cribier, which involved 129 patients, there was not a single case of trunk, neck, or face involvement. I also have never seen a photograph of EN outside the legs and arms. 

Despite this, the laundry list of “legs, arms, trunk, neck and face” are in many official descriptions of EN. When I try to dig into citations, they usually point to a single article from 1999 called “Diagnosis: erythema nodosum or not?” which in turn references an 1860 medical dictionary definition of EN. 

On the other hand, a quick search of the terms “erythema nodosum,” “face,” and “neck” turns up many articles about Sweet’s syndrome, another type of rash which can look like EN on the legs but can spread all over the body. Could this be another case of mistaken identity? Sweet’s syndrome was only described in 1964 after all. Even if the missing article has evidence that EN was seen on someone’s face, this is obviously an area that needs further research. 

In conclusion, yes, EN can appear on soft tissues of the legs and arms... but I have not seen evidence that it can spread to the trunk, neck, or face. 

Edit (9/14/2016): Several readers of this blog wrote in after this post, saying they have had erythema nodosum nodules on their trunks and necks. I have even received some photos. None of them describe a biopsy being done on these trunk or neck nodules, possibly because a leg nodule biopsy was already highly suggestive of EN. 

My concern still stands: EN has been seen multiple times with other rashes, some of them similar in appearance. Has anyone, ever, positively biopsied EN rashes on the trunk or neck? Have they been documented in a clinical setting? 

References:  Dermatology (Braun-Falco et al, 2000) (full text online)  Erythema nodosum and associated diseases. A study of 129 cases (Cribier et al, 1998)  Nodal Fever (Alfred Austin Lendon, 1905) An Acute Febrile Neutrophilic Dermatosis (R.D. Sweet, 1964)

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What is a Prodrome?

According to Wikipedia, a prodrome is “an early symptom (or set of symptoms) that might indicate the start of a disease before specific symptoms occur.” 

For example, people with Parkinson’s disease often lose their sense of smell before getting any other symptoms. Loss of smell is a prodromal symptom for Parkinson’s. Sometimes prodromal symptoms can be a clue about what to expect in the future, but they are usually not very specific. 

Erythema nodosum (EN) often has a prodromal stage. One to three weeks before the EN nodules actually appear, you might experience a low fever, a cough, weight loss, joint pains, and a generally uneasy, sick feeling. 

Since EN is often caused by tuberculosis and strep throat, this makes sense! Those diseases make you feel terrible. But the prodromal stage can happen no matter what is causing your EN, even if you don’t have another illness. According to American Family Physician, it can occur “regardless of etiology.” 

Doctors have written about this prodromal period since at least 1905, but it lacks a specific explanation. Since EN nodules are probably a hypersensitivity reaction, it’s not surprising that they would come along with other undesirable immune responses. 

Fun fact: do you have IBD or Behçet’s? Erythema nodosum could actually be a prodromal symptom for your disease flares. 

Okay, maybe that’s not so fun. 

References:  Wikipedia - Prodrome  Smell Loss and Parkinson’s Disease  International Journal of Clinical Practice (EN and Behçet’s) American Family Physician (EN as a sign of systemic disease)  Dermatology Online Journal (A Review)  Wikipedia - Hypersensitivity 

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The Case of Kary R., Watercolor, Helen de Reyher

Watercolors from the book Nodal Fever by Dr. Alfred Austin Lendon, published in 1905. The patient, “Katy R.” had a chronic bowel disease, as did all of her siblings. Lendon described her EN as the longest-running case he had seen, with new nodes cropping up for 21 days straight. 

The first watercolor shows angry red splotches on her shins, with some on her knees. The second watercolor shows the healing stage, where her legs appear to be covered in big, fading bruises. The last sketch shows her legs mostly healed. 

Nodal Fever is out of copyright and free to download from Google Books. It is interesting to read such a thorough account of what doctors in 1905 knew about the disease. I will warn you that the author was very wrong about a few things... like the ethics of giving tuberculosis to children.