Erythema nodosum may be accompanied by systemic symptoms of arthralgia and fever, particularly in adults [4]. These may be the initial presentation.

Erythema nodosum is an inflammation of subcutaneous fat layers [2]. The lesions are deep, tender nodules most commonly seen on the shins, but may occur on any part of the body [2] [6]. They are usually more palpable than visible [2].

The lesions of erythema nodosum begin as red, tender nodules with poorly defined borders [2]. They vary in size from 2 to 6 cm. Lesions last about 2 weeks with new lesions appearing for months [2]. Lesions heal without any scaring [2].

Fifty percent of patients with erythema nodosum also have generalized arthralgia which usually precedes the rash [2]. Erythema, swelling, and tenderness of any joint, sometimes with effusions, may occur. Ankles, knees, and wrist are the most common sites. Joint and leg pain and stiffness may last for up to 6 months. Synovial fluid and rheumatoid factor are negative and there are no damaging changes to the joints [2] [4].

The relapse rate has been reported to be as high as 74% in idiopathic erythema nodosum [4], but rarely in patients whose disease is secondary to an underlying disease [4] [7].

• Fever

  Because of its nonspecific clinical presentation, Q fever with erythema nodosum is probably underestimated. Q fever should be evocated when facing unexplained erythema nodosum even if there is not other typical clinical manifestation of Q fever. [ncbi.nlm.nih.gov]

  Fungal infections Coccidioidomycosis (San Joaquin Valley fever) is the most common cause of erythema nodosum in the American Southwest. [emedicine.medscape.com]

• Malaise

  Erythema nodosum leprosum (ENL) is characterized by tender erythematous nodules, accompanied by fever, malaise, arthralgia, and systemic complications. [ncbi.nlm.nih.gov]

• Hodgkin Lymphoma

  We describe a patient with advanced Hodgkin lymphoma with B symptoms, preceded by erythema nodosum of the left shin by 12 weeks. This dermatologic entity cleared after the treatment for Hodgkin lymphoma, suggesting a true paraneoplastic reaction. [ncbi.nlm.nih.gov]

  Erythema nodosum is the most frequent dermatologic symptom in inflammatory bowel diseases, and it is strongly associated with Crohn disease. [11, 12] Hodgkin disease and lymphoma Erythema nodosum associated with non-Hodgkin lymphoma may precede the diagnosis [emedicine.medscape.com]

• Fatigue

  Erythema nodosum is often associated with a distressing symptomatology, including painful subcutaneous nodules, polyarthropathy, and significant fatigue. [ncbi.nlm.nih.gov]

  Snapshot A 25-year-old woman with a history of sarcoidosis presents with fever, fatigue, and joint pain over the past week. Yesterday, she developed a bruise-like and raised painful rash on her shins despite having no recent trauma to the area. [medbullets.com]

  When the nodules first appear, many patients may experience fatigue, fever, arthritic symptoms, headache, conjunctivitis, and gastrointestinal distress. In most cases, the nodules disappear after a few weeks without any scarring. [perridermatology.com]

  Valley fever (an immune reaction to a fungal infection, such as coccidiomycosis or histoplasmosis) Inflammatory bowel disease, such as ulcerative colitis or Crohn's disease Other symptoms that can be seen with E. nodosum include fever, joint aches, fatigue [sharecare.com]

• High Fever

  At the initial visit, she showed high fever of 40 C, injection of the oropharynx, cervical lymphadenopathy, and red-purple cutaneous nodules, particularly on the lower limbs. She complained of severe pain in the neck and cutaneous lesions. [ncbi.nlm.nih.gov]

  Bullous and ulcerative ENL: Rare cases of unusual ENL reactions have been reported and are characterized by superficial bullous ulcerative cutaneous lesions associated with high fever, malaise and edema. [dermatologyadvisor.com]

  One month later, the patient consulted in the Emergency Department for asthenia, malaise, high fever, and arthralgias that did not improve with non-steroidal antiinflammatory drugs (NSAIDs). [longdom.org]

• Epigastric Pain

  A woman in her thirties presented with a 3-week history of jaundice, malaise, itching, nausea, decreased appetite, weight loss, dark orange urine and intermittent non-radiating epigastric pain. [ncbi.nlm.nih.gov]

• Benign Paroxysmal Positional Vertigo

  González-Gay, Benign Paroxysmal Positional Vertigo and Clinical Test of Sensory Interaction and Balance in Ankylosing Spondylitis, Otology & Neurotology, 10.1097/MAO.0b013e3182016534, 32, 2, (278-283), (2011). Neil Cox, J. L. Jorizzo, J. F. [doi.org]

• Arthritis

  But patients with only arthritis compared to patients with EN and arthritis did not show a significant difference in C allele frequency (p 0.270; OR 0.64, CI: 0.29-1.42). [ncbi.nlm.nih.gov]

  […] to demonstrate the aseptic reactive nature of the arthritis. [academic.oup.com]

  Further testing revealed that thalidomide also has a significant anti-inflammatory effect in the treatment of rheumatoid arthritis and… Read More [britannica.com]

• Arthralgia

  Although arthralgia and AGPB can be recognized together, EN and Achilles tendinitis are rare manifestations seen in patients with AGPB. In this case report, we suggest arthralgia, EN, and Achilles tendinitis could coexist with AGPB. [ncbi.nlm.nih.gov]

  A majority of patients with erythema nodosum also have arthralgia, painful joints, and stiffness. What causes erythema nodosum? The cause of erythema nodosum s is not fully understood. [symptoma.com]

  arthralgias 5 days later, but no subcutaneous nodules Zimmer et al. [11] F, 59 ALM (lymph node, lung, liver, bone) V Painful nodules in arms and legs 7 days Mild arthralgias Septolobular neutrophilic panniculitis Etoricoxib No Resolution in 4 weeks Shina [longdom.org]

• Eruptions

  Convert to ICD-10-CM : 695.2 converts directly to: 2015/16 ICD-10-CM L52 Erythema nodosum Clinical Information An erythematous eruption commonly associated with drug reactions or infection and characterized by inflammatory nodules that are usually tender [icd9data.com]

  Skin manifestations are uncommon including transient punctiform rashes, purpuric, or maculopapular eruptions. Erythema nodosum have seldom been reported. [ncbi.nlm.nih.gov]

  Diagnosis There are a few other skin eruptions that mimic erythema nodosum, so the physician may have to perform a biopsy to sort them out. [medical-dictionary.thefreedictionary.com]

  In 30% of cases of idiopathic erythema nodosum, eruptions may last more than 6 months. Erythema nodosum is self-limited and resolves without sequelae. Erythema nodosum may occur at any age. [symptoma.com]

• Exanthema

  L, 680-709) Infections Bacterial skin disease Staphylococcus (Staphylococcal scalded skin syndrome, Impetigo, Boil, Carbuncle) · Strep (Impetigo) · Corynebacterium (Erythrasma) Viral skin disease Wart · Molluscum contagiosum · Erythema infectiosum · Exanthema [wikidoc.org]

• Furunculosis

  The patient was diagnosed initially and treated as a case of furunculosis with poor clinical response. The skin biopsy showed features consistent with subacute nodular panniculitis. [ncbi.nlm.nih.gov]

• Foot Ulcer

  Amos Lal, Jamal Akhtar and Alwyn Rapose, A Rare Cause of Painful Nonhealing Foot Ulcers, Infectious Diseases in Clinical Practice, 10.1097/IPC.0000000000000651, 26, 6, (371-373), (2018). Alisa Brandon, Asfandyar Mufti and R. [doi.org]

There are no specific tests for erythema nodosum. The following laboratory studies may be helpful:

• Throat culture to exclude group A beta-hemolytic streptococcal infection.
• Complete blood count: Increased white blood count, with preponderance of neutrophils and bands [2] [4]. 
• Erythrocyte sedimentation rates: Significantly elevated in 76% of patients [4] [8].
• Anti-streptolysin-O titer: Elevated with streptococcal infections (10%), but normal levels do not exclude streptococcal infection [8]. 
• Stool analysis to exclude infection by Yersinia, Salmonella, and Campylobacter organisms.

Imaging 

• Chest radiographs to exclude sarcoidosis and tuberculosis and to identify hilar adenopathy [8].
• X-rays of the joints are generally normal, showing no bony deformities or effusions [4].

Other tests

Intradermal skin tests for tuberculosis, Yersinia, and coccidioidomycosis. Positive tuberculin test occurred in almost 50% of cases [2] [8].

Procedures

• Deep skin biopsy, including the hypodermis, shows inflammation [6]. It is only recommended for diagnostically difficult cases. 
• Blood cultures

• Bilateral Hilar Adenopathy

  SARCOIDOSIS Sarcoidosis causes up to one fourth of erythema nodosum cases. 2, 4, 7 Radiographic imaging often reveals bilateral hilar adenopathy, with one study reporting chest radiography or computed tomography findings of bilateral hilar adenopathy [aafp.org]

  Loefgren’s syndrome, a specific variant of sarcoidosis, describes the triad of bilateral hilar adenopathy, erythema nodosum, and polyarthralgia or polyarthritis. Uncommon Findings: Cutaneous ulceration is extremely rare. [rheumaknowledgy.com]

• Elevated Sedimentation Rate

  Elevated Sedimentation Rate (ESR) was 37 mm/hr (normal range for women 0-29 mm/hr). Erythema nodosum (EN) was highest on the differential diagnosis, and the patient was referred to Dermatology for clinical confirmation of the diagnosis. [ijcrimedicine.com]

• Coxiella Burnetii

  Serological testing for Coxiella burnetii was positive. Treatment consisted with doxycycline for 2 weeks. Evolution was favorable. The patient completely recovered and had no evidence of skin lesion 1 month later. [ncbi.nlm.nih.gov]

Most cases of erythema nodosum are self-limited and require only treatment of the symptoms using non-steroidal anti-inflammatory medications (NSAIDs), cool compresses, elevation, and bed rest [2]. Activity should be restricted in the acute phase when pain and swelling are significant [4].

If a drug reaction is suspected, it should be eliminated. Corticosteroids may be effective but are not usually necessary or recommended [6]. Oral corticosteroids are effective, but only temporarily [2]. Associated adverse effects of these drugs restrict their use to severe cases for short term use. Recurrence of erythema nodosum following discontinuation of treatment is common, and underlying infectious disease may be worsened [6].
Intralesion corticosteroids can be effective some cases [2].
Oral saturated solution of potassium iodide and colchicine, in patients unresponsive to non-steroidal anti-inflammatory drugs, have been shown to be effective [2]. Treatment of the underlying trigger is imperative and may result in rapid resolution of erythema nodosum [2].

Erythema nodosum is generally benign and resolves without complications. The duration of symptoms can be extensive, lasting up to six months.

Erythema nodosum is one of a group of common inflammatory diseases of the hypodermis [6]. Its etiology is unknown, but it is considered to be a hypersensitivity reaction to a systemic trigger [6].

Erythema nodosum is itself a self-limited, benign disorder but can be due to a serious underlying disease that triggers its appearance. Triggers include granulomatous diseases, malignancy (lymphoma and leukemia), inflammatory bowel diseases, and severe infections [5].

The condition usually begins abruptly with flulike symptoms: fever, malaise, and general aches. These symptoms are followed by the painful rash within 1-2 days [7]. Arthralgia may precede or accompany the rash. In cases associated with infection lesions heal in 1-2 months. Those due to active disease may last up to 6 months. In 30% of cases of idiopathic erythema nodosum, eruptions may last more than 6 months [7]. Erythema nodosum is self-limited and resolves without sequelae [7].

Erythema nodosum may occur at any age. Peak incidence is between the ages of 18-34 years, but varies with etiology [7] [8].
Incidence rates vary widely by country, with a median rate of 2.4 cases per 10,000 per year [1]. Erythema nodosum occurs more often in women, with a male-to-female ratio of 1:4 [2] [7].

It has been theorized that erythema nodosum is due to a T-cell mediated response between common antigens and the skin [3], suggesting that genetic factors play a role in determining who will develop these cutaneous symptoms [3].

The most common causes of erythema nodosum are streptococcal infection, tuberculosis, and sarcoidosis [7] [9]. There are many other causes associated with the disorder, they include [7] [10]:

• Bacterial infections: Streptococcal, tuberculosis [3] [2], mycoplasma pneumonia, lymphogranuloma venereum, Salmonella, Yersinia enterocolitica and Campylobacter infection [2]. 
• Fungal infections: Coccidioidomycosis (the most common fungal cause in Southwest America), histoplasmosis, and blastomycosis [2]. 
• Drug reactions: Sulfonamides, halide agents, gold, sulfonylureas, and oral contraceptives [2]. Drug-induced erythema nodosum is rare [6].
• Gastrointestinal pathologies such as: Ulcerative colitis and Crohn disease [5]. With these underlying diseases the eruption usually resolves when the disease subsides [2].
• Hodgkin disease and lymphoma
• Sarcoidosis 
• Pregnancy: Some patients develop erythema nodosum during pregnancy, most frequently during the second trimester [6]. 

In erythema nodosum, approximately 50% of cases are idiopathic, where no definite etiology is found. Of the remaining cases, the most common etiologies are primary tuberculosis (18%) [6] [10], post-streptococcal infection (16%), sarcoidosis (12%), inflammatory bowel diseases (IBD) (4%), Behçet's disease (2%), and pregnancy (2%) [7]. The numbers differ significantly in the pediatric population with 55 % due to infectious diseases (half from streptococcal infections) and 22% from non-infectious inflammatory diseases [3]. None of the reported cases were from tuberculosis and only 22% of the patients had no associated disease [3].

Since inflammatory bowel disease often presents with erythema nodosum, the presence of this symptom should prompt healthcare providers to suspect an underlying inflammatory disease [4].

There is no clear means of preventing erythema nodosum since the exact cause is not known. Prevention of the underlying triggers for the disease may decrease its incidence. Prevention of streptococcal infections, tuberculosis, enterobacterial infections may be helpful.

Treatment and control of inflammatory diseases such as inflammatory bowel disease and Crohn disease may decrease the occurrence and recurrence of erythema nodosum, as well.

Erythema nodosum (EN) refers to an erythematous, nodular eruption that usually occurs on the extensor surfaces of the lower legs [1]. It is generally an acute episodic condition, though chronic or recurrent erythema nodosum may occur [2].

Erythema nodosum is thought to be a hypersensitivity reaction triggered by some systemic diseases or drugs. It is, however, idiopathic in 50% of cases [1] [3] [4].

Erythema nodosum is a self-limited disorder. Recovery is complete with no further complications or sequelae. Treatment is symptomatic for this disorder. However, treatment of the triggering mechanism, if known, needs to be instituted first [5].

What is erythema nodosum?

Erythema nodosum is an acute nodular rash causing red, tender raised areas on the anterior shins and occasionally on other surfaces of the body. It is a benign disorder and resolves within 2 weeks to several months without complications. However, though not serious itself, it may be triggered by serious underlying conditions such as: tuberculosis, strep infections, inflammatory bowel disease, drug reactions, or malignancy.

What are the symptoms?

The primary symptom of erythema nodosum is the distinctive nodular rash. It may be accompanied by flu-like symptoms, fever and malaise. A majority of patients with erythema nodosum also have arthralgia, painful joints, and stiffness.

What causes erythema nodosum?

The cause of erythema nodosum s is not fully understood. It is thought to be a hypersensitivity reaction triggered by an immune response to an antigen. This causes inflammation of the hypodermal fatty layer of the subcutaneous tissue.

Who gets erythema nodosum?

Anyone of any age can get erythema nodosum, though it is most frequent in people age 18 to 35 years. It occurs 2 to 4 times more often in women than men.

How is it diagnosed?

There is no specific test for erythema nodosum. It is diagnosed by the clinical symptoms, primarily the characteristic lesions, and patient history. Certain blood tests help to confirm the diagnosis. A biopsy of the lesions can confirm the diagnosis in some cases.

How is erythema nodosum treated?

Erythema nodosum is treated with non-steroidal anti-inflammatory medications, ibuprofen, aspirin, and naproxen, bed rest and cool compresses. In patients who do not respond to this treatment corticosteroids may be used. Treatment of the underlying trigger, if known, is essential in the treatment of this disorder.

What are the complications?

There are no significant complications to erythema nodosum, though because of its long duration and the need for rest and decreased activity it does interfere with daily activities and quality of life. The underlying disease triggering erythema nodosum may have significant complications and even be life threatening.

1. Nguyen GC, Torres EA, Regueiro M, et al. Inflammatory bowel disease characteristics among African Americans, Hispanics, and non-Hispanic Whites: characterization of a large North American cohort. Am J Gastroenterol. 2006;101(5):1012-23.
2. Lebwohl M, Lebwohl O. Cutaneous Manifestations of Inflammatory Bowel Disease. Inflam Bowel Diseases. 1998; 4(2): 142-149.
3. Kakourou T, Drosatou P, Psychou F, Aroni K, Nicolaidou P. Erythema nodosum in children: a prospective study. Jour Am Acad Dermatol. 2001;44(1):17-21. 
4. Faulkes RE. Upper limb erythema nodosum: the first presentation of Crohn’s disease. Clinical Case Reports. 2013; 10(1002/ccr3.87): 1-2.
5. Bottone EJ. Yersinia enterocolitica: the charisma continues. Clin Microbiol Rev. 1997;10(2):257-76.
6. Bergler-Czop B, Lis-Swiety A, Kaminska-Winciorek G, Brzezinska-Wcisło L. Erythema nodosum caused by ascariasis and Chlamydophila pneumoniae pulmonary infection: a case report. FEMS Immunol Med Microbiol. 2009; 57:236–238.
7. Mert A, Ozaras R, Tabak F, Pekmezci S, Demirkesen C, Ozturk R. Erythema nodosum: an experience of 10 years. Scand J Infect Dis. 2004;36(6-7):424-7.
8. Puavilai S, Sakuntabhai A, Sriprachaya-Anunt S, Rajatanavin N, Charuwichitratana S. Etiology of erythema nodosum. J Med Assoc Thai. 1995;78(2):72-5.
9. Hassink RI, Pasquinelli-Egli CE, Jacomella V, Laux-End R, Bianchetti MG. Conditions currently associated with erythema nodosum in Swiss children. Eur J Pediatr. 1997;156(11):851-3.
10. Mert A, Ozaras R, Tabak F, Ozturk R. Primary tuberculosis cases presenting with erythema nodosum. Jour of Dermatol. 2004;31(1):66-8.