Erythema nodosum is a perplexing inflammatory condition that causes painful, red bumps to appear on the skin, most commonly on the shins. While it can be alarming and uncomfortable for patients, erythema nodosum is usually self-limited and resolves on its own within several weeks. However, prompt recognition and appropriate management by healthcare providers are essential for minimizing complications and ruling out underlying causes.
This article provides a comprehensive overview of erythema nodosum, including its clinical presentation, etiology, diagnostic approach, and treatment strategies. By understanding the key features and management principles of this condition, clinicians can provide optimal care for patients presenting with these distinctive skin lesions. The goal is to alleviate symptoms, identify and address any triggering factors, and ensure a favorable prognosis for those affected by erythema nodosum.
What is Erythema Nodosum?
Erythema nodosum (EN) is a common acute nodular septal panniculitis, characterized by the sudden onset of erythematous, firm, solid, deep nodules or plaques that are painful on palpation and mainly localized on extensor surfaces of the legs. These nodules are characterized by a typical histological appearance regardless of the etiology, marked by acute inflammation of the dermo-hypodermic junction and interlobular septa of the hypodermic fat, evolving without necrosis or sequelae.
Erythema nodosum is an acute or recurrent hypersensitivity reaction to a variety of antigens with a clear female predominance that may be associated with several different stimuli or pathological conditions. It presents as tender red nodules on the anterior shins, and less commonly on the thighs and forearms. The nodules are usually bilateral and symmetrical.
EN is the most common clinical form of acute nodular hypodermis. It occurs more often in women between 25 and 40 years but can be observed at any age. Compared to men, women are affected three to six times more. It is rare without sex predominance in the pediatric population.
The nodules of erythema nodosum are usually found symmetrically on the shins. They can be as big around as a penny or a lime, and may be tender and swollen off and on for a few weeks. The nodules can take 1-2 months to heal completely, and may look like bruises as they fade. They usually do not leave scars, but sometimes a small pit in the skin may remain where the fat layer has been injured.
Besides the characteristic skin lesions, more than 50% of patients with EN also complain of systemic symptoms such as:
- Low-grade fever
- Fatigue
- Joint and muscle pain
- Swollen ankles
- Hilar adenopathy
The joint pain and swelling may resolve in a few days, but the pain can persist for a few months. There is usually no joint destruction, and the synovial fluid is sterile.
In summary, erythema nodosum is an inflammatory disorder of the subcutaneous fat characterized by tender, red nodules that typically appear on the shins. It has a female predominance and is associated with a variety of triggers, most commonly infections like streptococcal pharyngitis. The nodules of EN are self-limiting but can be recurrent. Prompt recognition and treatment of any underlying cause is key to management.
Symptoms of Erythema Nodosum
The hallmark of erythema nodosum is tender, erythematous, subcutaneous nodules that typically are located symmetrically on the anterior surface of the lower extremities. The nodules are usually bilateral and symmetrical.
Appearance of Nodules
The nodules of erythema nodosum are usually found symmetrically on the shins. They can be as big around as a penny or a lime, and may be tender and swollen off and on for a few weeks. The nodules can take 1-2 months to heal completely, and may look like bruises as they fade. They usually do not leave scars, but sometimes a small pit in the skin may remain where the fat layer has been injured.
Systemic Symptoms
Besides the characteristic skin lesions, more than 50% of patients with EN also complain of systemic symptoms such as:
- Low-grade fever
- Fatigue
- Joint and muscle pain
- Swollen ankles
- Hilar adenopathy
The joint pain and swelling may resolve in a few days, but the pain can persist for a few months. There is usually no joint destruction, and the synovial fluid is sterile.
In summary, the key symptoms of erythema nodosum include painful, red nodules on the shins that may take weeks to months to resolve completely. Systemic symptoms like fever, fatigue, joint pain, and swollen ankles are also commonly reported. Prompt recognition of these signs is important for diagnosing and managing the underlying cause of erythema nodosum.
Causes of Erythema Nodosum
Erythema nodosum can be triggered by a variety of factors, including infections, medications, and underlying medical conditions. In many cases, the exact cause remains unknown (idiopathic). Some of the most common identifiable causes of erythema nodosum include:
Infections
Streptococcal infections, particularly streptococcal pharyngitis, are the most common infectious cause of erythema nodosum, accounting for 28-48% of cases. Other bacterial infections such as tuberculosis, yersiniosis, salmonellosis, campylobacter gastroenteritis, and mycoplasma pneumonia have also been associated with erythema nodosum.
Viral infections like infectious mononucleosis, hepatitis B and C, and human immunodeficiency virus (HIV) can also trigger erythema nodosum. Fungal infections, including coccidioidomycosis, histoplasmosis, and blastomycosis, have been implicated in some cases, particularly in endemic regions.
Medications
Various medications have been reported to cause erythema nodosum in 3-10% of cases. The most commonly associated drugs include:
- Antibiotics (e.g., sulfonamides, penicillins)
- Oral contraceptives
- Bromides and iodides
- TNF-alpha inhibitors
Some vaccines, such as those for tetanus, diphtheria, and acellular pertussis, BCG, hepatitis B, human papillomavirus, malaria, rabies, smallpox, typhoid, and cholera, have also been linked to the development of erythema nodosum.
Underlying Medical Conditions
Several systemic diseases can present with erythema nodosum as a manifestation:
- Sarcoidosis: Erythema nodosum is associated with sarcoidosis in 11-25% of cases and may be part of Löfgren’s syndrome, which includes bilateral hilar adenopathy.
- Inflammatory bowel disease: Crohn’s disease and ulcerative colitis can cause erythema nodosum in 1-4% of cases.
- Behçet’s disease: Up to 50% of patients with Behçet’s syndrome may develop erythema nodosum.
- Pregnancy: Erythema nodosum occurs in 2-5% of pregnancies, possibly due to hormonal changes.
- Malignancies: Although rare, erythema nodosum may be a sign of underlying malignancies such as lymphoma, leukemia, or solid tumors.
Other conditions that have been associated with erythema nodosum include systemic lupus erythematosus, rheumatoid arthritis, and Sjögren’s syndrome.
In summary, erythema nodosum is a reactive process that can be triggered by various infectious agents, medications, and systemic diseases. A thorough evaluation is essential to identify the underlying cause and guide appropriate management. However, in many cases, the etiology remains idiopathic despite extensive investigations.
Diagnosis of Erythema Nodosum
The diagnosis of erythema nodosum is primarily based on clinical presentation and histopathological findings. A thorough medical history and physical examination are essential to identify the underlying cause. The initial work-up should include a detailed assessment of symptoms, recent medications, and any potential triggers.
Physical Examination
The clinical examination allows specifying the characteristics of the nodules:
- 10 to 40 mm in diameter
- Warm and firm on palpation, which accentuates their painful character
- Mobile in relation to the deep planes
Edema of the ankles is often present. Hilar adenopathy may also occur and be confused with sarcoidosis.
Laboratory Tests
The initial diagnostic work-up should aim to identify common etiologies. Laboratory tests and imaging must be guided by the clinical findings. However, the etiology may vary depending on factors such as race and geographic location of the patient. These factors also determine the laboratory tests and imaging studies that must be requested.
We suggest that an initial laboratory work-up should include:
- Complete blood count
- Erythrocyte sedimentation rate
- C-reactive protein
- Antistreptolysin O titer
- Throat swab culture
A pregnancy test must be done in all women of child-bearing age. Additional tests may be performed based on clinical suspicion:
- Sputum acid-fast bacilli smear, mycobacterial culture, and tuberculin skin test or interferon-γ release assay in TB endemic regions and with abnormal chest x-rays
- Stool examination, culture, and coproparasitoscopic stool study if diarrhea, abdominal pain, or other gastrointestinal discomfort is present
Leukocytosis, an elevated C-reactive protein level, an accelerated erythrocyte sedimentation rate, the presence of prolonged fever, cough, sore throat, diarrhea, arthritis, non-relapsing EN, and an abnormal chest x-ray were predictors of secondary EN, while recurrent EN predicted primary EN.
Imaging Studies
Chest radiography should be performed as part of the initial workup to exclude sarcoidosis and tuberculosis and to document hilar adenopathy.
If the initial work-up is inconclusive, further laboratory testing and imaging studies should be performed. No test abnormalities specific to EN have been described. Unfortunately, in most cases, no specific etiology can be found; therefore, these patients are considered as idiopathic or primary EN.
Treatment of Erythema Nodosum
The treatment of erythema nodosum typically focuses on managing symptoms and addressing the underlying cause, if identified. Treatment options include medications, lifestyle modifications, and monitoring for potential complications.
Medications
Several medications can help alleviate the symptoms of erythema nodosum:
- Nonsteroidal anti-inflammatory drugs (NSAIDs): NSAIDs like ibuprofen or naproxen can help reduce pain, swelling, and inflammation associated with erythema nodosum lesions. However, caution should be exercised in patients with inflammatory bowel disease, as NSAIDs may exacerbate their symptoms.
- Corticosteroids: In severe cases or when NSAIDs are ineffective, oral corticosteroids may be prescribed to reduce inflammation. Intralesional corticosteroid injections can be used for particularly painful or persistent nodules.
- Potassium iodide: Potassium iodide solution, taken orally, has been shown to provide symptomatic relief in some cases of erythema nodosum. However, it should be used with caution in patients with thyroid disorders.
Lifestyle Modifications
In addition to medications, certain lifestyle changes can help manage erythema nodosum:
- Rest: Patients should be advised to rest and elevate the affected limbs to reduce swelling and discomfort.
- Compression stockings: Wearing compression stockings can help minimize swelling and provide support to the affected areas.
- Avoiding triggers: If a specific trigger, such as a medication or an allergen, has been identified, patients should be advised to avoid exposure to prevent future episodes.
Potential Complications
While erythema nodosum is usually self-limiting, it is essential to monitor for potential complications:
- Underlying conditions: Erythema nodosum can be a manifestation of various underlying conditions, such as infections, inflammatory disorders, or malignancies. Prompt identification and treatment of the underlying cause are crucial to prevent further complications.
- Recurrence: Some patients may experience recurrent episodes of erythema nodosum. In such cases, a thorough evaluation for an underlying chronic condition should be conducted.
- Post-inflammatory hyperpigmentation: As the erythema nodosum lesions heal, they may leave behind areas of hyperpigmentation, which can be cosmetically concerning for some patients. Reassurance and counseling may be necessary.
In summary, the treatment of erythema nodosum involves a combination of medications to manage symptoms, lifestyle modifications to promote healing, and monitoring for potential complications. Identifying and treating any underlying conditions is essential for the successful management of erythema nodosum.
Prognosis and Outlook
The prognosis for patients with erythema nodosum is generally good, with most cases resolving spontaneously within a few weeks to months. However, there is a small risk of recurrence, especially if the underlying cause is not identified and treated.
The skin lesions of erythema nodosum often take several weeks to months to resolve completely. During the healing process, the nodules may change in appearance, turning from bright red to a bruise-like purple or yellowish color before fading away. In most cases, the lesions heal without leaving any scars or permanent changes in skin pigmentation.
While the skin manifestations of erythema nodosum are self-limited, it is crucial to identify and address any underlying conditions to prevent future episodes and potential complications. If an associated disorder, such as streptococcal infection, sarcoidosis, or inflammatory bowel disease, is found, appropriate treatment should be initiated to manage the condition and reduce the risk of recurrence.
In rare cases, erythema nodosum can be persistent or recurrent, particularly when the underlying cause is not effectively treated or if the condition is idiopathic. These chronic or recurrent cases may require long-term management with medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs), potassium iodide, or corticosteroids, to control symptoms and prevent new lesions from developing.
Overall, with proper diagnosis, treatment of associated conditions, and supportive care, most patients with erythema nodosum can expect a favorable outcome with complete resolution of the skin lesions and no long-term complications.
Conclusion
Erythema nodosum is a perplexing yet manageable inflammatory condition that requires prompt recognition and appropriate care from healthcare providers. By understanding the key clinical features, potential triggers, and diagnostic approach, clinicians can effectively identify and treat this condition, minimizing complications and ensuring a favorable prognosis for affected patients. While the exact cause may remain elusive in some cases, addressing any underlying disorders and providing supportive care are essential for successful management.
With proper treatment and monitoring, most patients with erythema nodosum can expect complete resolution of their symptoms within a few weeks to months. Although recurrence is possible, particularly in idiopathic cases, the overall outlook for individuals affected by this condition is positive. By staying informed and proactive in their approach, healthcare providers can play a crucial role in helping patients navigate the challenges of erythema nodosum and achieve optimal outcomes.