Erythema nodosum



Erythema nodosum


Robert A. Allen


Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports


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(Courtesy of Herbert B. Allen, MD, Drexel University, Philadelphia, PA, USA.)


Erythema nodosum (EN) is a septal panniculitis that presents as tender, erythematous nodules and plaques located primarily on the extensor surfaces of the lower extremities. There is a predilection for females. Numerous etiologies have been implicated, including chronic inflammatory states, infections, reactions to medications, and, rarely, malignancies. There is a tendency towards spontaneous regression, which usually occurs within 6 months after the onset of the first lesions.



Management strategies


Treatment of EN depends on the suspected or documented etiology, if known. Common causes include infections, chronic inflammatory states, and drug reactions. Unfortunately, even after extensive evaluations, many cases are classified as idiopathic.


Infectious agents include, but are not limited to, multiple bacteria, viruses, and fungi. Bacterial and protozoan causes include Streptococcus, Yersinia enterocolitica, Salmonella enteritidis, Giardia lamblia, Shigella, Klebsiella spp., tuberculosis, brucellosis, psittacosis, cat scratch disease, chancroid, tularemia, rickettsiosis, and Campylobacter. Viral causes include hepatitis B, hepatitis C, HIV, and Crimean-Congo hemorrhagic fever. Fungal infectious agents causing blastomycosis, sporotrichosis, coccidioidomycosis, histoplasmosis, nocardiosis, and fungal kerions have also been implicated. Although all these infectious agents have been implicated in various reports, the streptococcus remains the most likely causative agent.


Patients with certain diseases that are characterized by chronic inflammation may develop EN. The most common disease is sarcoidosis but inflammatory bowel disease (Crohn disease and ulcerative colitis), Behçet syndrome, Sweet syndrome, pyoderma faciale, and chronic abscesses have been associated.


Medications are common inciting agents. The most likely cause is oral contraceptive use, but medicines such as iodides, bromides, quinolones, and sulfonamides have been implicated. Lidocaine injections, aromatase inhibitors, all-trans-retinoic acid, propylthiouracil, granulocyte colony-stimulating factor, echinacea supplements, and glatiramer acetate are thought to be causative.


Malignancies such as leukemias, lymphomas, myelodysplastic syndrome, and parathyroid carcinoma have been implicated. In cancer patients it may be difficult to determine the definitive cause of the EN because of the multiple treatments and possible chronic inflammation that can occur.


Skin biopsy is generally not necessary if the history and physical signs are suggestive of EN. The pathology should demonstrate inflammation in the septae between fat lobules of the subcutis. The type of inflammation may vary between acute and chronic inflammation, including multinucleated giant cells. Other findings can include fibrosis, increased thickness of the intralobular septae, and radial arrays of macrophages around blood vessels. A biopsy is usually helpful in ruling out other forms of panniculitis, and if an infectious cause is in the differential diagnosis, some tissue may be sent for culture and stains to look for organisms.


Treatment consists primarily of bed rest, activity reduction, non-steroidal anti-inflammatory agents (NSAIDs), and potassium iodide. Various NSAIDs have been used successfully, including naproxen and indomethacin. Potassium iodide has recently regained popularity but may be difficult to obtain because of stockpiling by national governments. We recommend a supersaturated solution of potassium iodide of five drops three times a day in orange juice to mask the taste. One drop per dose is added each day until clinical effectiveness is achieved. Hypothyroidism can result from long-term use of potassium iodide. Hydroxychloroquine 200 mg twice a day has been used with limited success in EN. Dapsone was successful in a patient who developed EN after starting isotretinoin for acne fulminans. Systemic corticosteroids may also be helpful in refractory cases, or to ‘jump start’ therapy.



Specific investigations












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Aug 7, 2016 | Posted by in Dermatology | Comments Off on Erythema nodosum

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