Erythema Nodosum

Definition:

• A common acute nodular septal panniculitis characterized by the sudden onset of erythematous, firm, solid, deep nodules or plaques, painful on palpation, mainly on the extensor surfaces of the legs. It features acute inflammation of the dermo-hypodermic junction and interlobular septa of the hypodermic fat without necrosis or sequelae.

Etiology:

• Idiopathic: No obvious cause found in about 30% to 50% of cases.
• Infections:
  • Bacterial: Streptococcal infections (most common), tuberculosis, leprosy, Yersinia, salmonella, campylobacter, mycoplasma pneumonia, tularemia, cat scratch disease, leptospirosis, brucellosis, psittacosis, chlamydia.
  • Viral: Infectious mononucleosis, hepatitis B and C, HIV, herpes simplex virus, Epstein-Barr virus, para vaccinia.
  • Fungal: Coccidioidomycosis, histoplasmosis, blastomycosis.
  • Parasitic: Amebiasis, giardiasis.
• Noninfectious:
  • Drugs: Antibiotics (penicillins, sulfonamides), oral contraceptives, bromides, iodides, TNF-alpha inhibitors.NSAIDS
  • Malignancies: Leukemia, lymphoma, occult malignancies.
  • Inflammatory Bowel Disease: Crohn’s disease, ulcerative colitis.
  • Miscellaneous: Sarcoidosis (Lofgren syndrome), pregnancy, Whipple disease, Behcet disease.

Epidemiology:

• More common in women aged 25-40, but can occur at any age. Women are affected 3-6 times more than men. Rare in pediatric populations without sex predominance. Incidence varies with ethnic and geographical differences due to etiological factors. Familial cases are often infection-related.

Pathophysiology:

• A nonspecific cutaneous reaction to various antigens, likely immunologically mediated through a type IV delayed hypersensitivity response. Possible mechanisms include immune complex deposition in subcutaneous fat venules, production of oxygen free radicals, TNF-alpha, and granuloma formation.

Histopathology:

• Skin biopsy is typically not required for diagnosis but can be useful in atypical cases. It shows lymphohistiocytic infiltration of interlobular septa, sparing fat lobules and vessels.

Clinical Presentation:

• Prodromal Phase: Fever, joint pain, abdominal pain, often with nasopharyngeal infection.
• Stade Phase:
  • Quick onset in 1-2 days with fever
  • persistent joint pain
  • appearance of nodules primarily on the shins and knees.
  • Nodules
    • bilateral & symmetrical
    • oval, round or arciform
    • warm
    • firm
    • painful
    • found on the anterior lower legs, knees and arms and rarely on the face and neck.
    • initially bright to deep red. 
    • Pain worsens with standing, leading to a preference for lying down with raised legs.
    • Ankle edema and hilar adenopathy may be present.
• Regressive Phase: Spontaneous resolution over 4-8 weeks, with nodules fading without necrosis, ulceration, or scarring. Recurrence is possible.

Associated Symptoms:

• Over 50% of patients report joint and muscle pain, with occasional joint swelling and morning stiffness. The pain may last for months but typically does not cause joint destruction.

Diagnosis:

• Primarily clinical, based on history and physical examination.
• Complementary tests may be needed for etiological diagnosis
• Appropriate tests may include:
  • Complete blood count with differential, C-reactive protein levels (infectious and inflammatory causes)
  • Chest X-ray (tuberculosis and sarcoidosis)
  • Throat swab and anti-streptolysin O and streptodornase serology (streptococcal infection)
  • Viral serology (preferably two samples at four-week intervals)
  • Stool culture and evaluation for ova and parasites in patients with gastrointestinal symptoms
  • Mantoux test or QuantiFERON gold
  • Deep incisional or excisional skin biopsy

Treatment and Management:

• Rest: Extended rest and possibly work stoppage.
• Symptomatic Treatment: Analgesics and venous compression to reduce pain. Steroidal anti-inflammatory drugs and colchicine may be prescribed.
  • Systemic corticosteroids (1 mg/kg daily until resolution of erythema nodosum) may be prescribed if infection, sepsis, and malignancy have been ruled out.
  • Oral potassium iodide as a supersaturated solution (400–900 mg/day) may be prescribed for one month if available
• Etiologic Treatment: Antibiotics for streptococcal infections or anti-tuberculosis treatment as needed. In Löfgren syndrome, pulmonary radiographic monitoring is recommended.
• Interdisciplinary Care: Consultation with dermatologists or rheumatologists if diagnosis is uncertain. Pharmacists should review patient medications to avoid those that may cause EN.

Prognosis:

• Generally favorable, with spontaneous resolution. Recurrence is possible, but skin lesions typically do not scar or change pigmentation.

Pearls and Other Issues:

• EN is benign and self-limiting, but identifying and treating the underlying cause is crucial for resolution. Optimal care involves collaboration among healthcare providers to avoid unnecessary procedures and ensure appropriate management.