Doctor123.org

Erythema Nodosum

Doctor123.org

Erythema Nodosum

para>May have repeat outbreaks during pregnancy

Varies geographically depending on the prevalence of disorders associated with EN

Initial Tests (lab, imaging)

Deep-incisional or excisional skin biopsy including subcutaneous tissue; rarely necessary except in atypical cases with ulceration, duration >12 weeks, or absence of nodules overlying lower limbs (3)[C]

Admission Criteria/Initial Stabilization

Occasionally, admission may be needed for the antecedent illness (e.g., tuberculosis).

Monthly follow-up or as dictated by underlying disorder

11 Schwartz RA, Nervi SJ. Erythema nodosum: a sign of systemic disease. Am Fam Physician. 2007;75(5):695-700.22 Cribier B, Caille A, Heid E, et al. Erythema nodosum and associated diseases. A study of 129 cases. Int J Dermatol. 1998;37(9):667-672.33 Requena L, Yus ES. Erythema nodosum. Dermatol Clin. 2008;26(4):425-438.44 S ¡nchez Yus E, Sanz Vico MD, de Diego V. Miescher's radial granuloma. A characteristic marker of erythema nodosum. Am J Dermatopathol. 1989;11(5):434-442.55 Horio T, Imamura S, Danno K, et al. Potassium iodide in the treatment of erythema nodosum and nodular vasculitis. Arch Dermatol. 1981;117(1):29-31.66 Yurdakul S, Mat C, T ¼z ¼n Y, et al. A double-blind trial of colchicine in Beh §et's syndrome. Arthritis Rheum. 2001;44(11):2686-2692.

Rare pediatric variant has lesions only on palms or soles, often unilateral. Typically has a shorter duration in children than adults.

EPIDEMIOLOGY

  • 1 to 5/100,000/year
  • Predominant age: 20 to 30 years
  • Predominant sex: female > male (6:1) in adults

ETIOLOGY AND PATHOPHYSIOLOGY

  • Idiopathic: up to 55%
  • Infectious: 44%. Streptococcal pharyngitis (most common), mycobacteria, mycoplasma, chlamydia, mycoplasma, coccidiodomycosis, rarely can be caused by Campylobacter spp., ricketssiae, Salmonella spp., psittacosis, syphilis
  • Sarcoidosis: 11-25%
  • Drugs: 3-10%. sulfonamides amoxicillin, oral contraceptives, bromides, azathioprine, vemurafenib
  • Pregnancy: 2-5%,
  • Enteropathies: 1-4%. Ulcerative colitis, Crohn disease, Beh §et disease, celiac disease, diverticulitis
  • Rare causes: <1% (1)Fungal: dermatophytes, coccidioidomycosis, histoplasmosis, blastomycosisViral/chlamydial: infectious mononucleosis, lymphogranuloma venereum, paravaccinia, HIVMalignancies: lymphoma/leukemia, sarcoma, myelodysplastic syndromeSweet syndrome
  • Fungal: dermatophytes, coccidioidomycosis, histoplasmosis, blastomycosis
  • Viral/chlamydial: infectious mononucleosis, lymphogranuloma venereum, paravaccinia, HIV
  • Malignancies: lymphoma/leukemia, sarcoma, myelodysplastic syndrome
  • Sweet syndrome

RISK FACTORS

COMMONLY ASSOCIATED CONDITIONS

DIAGNOSIS

HISTORY

  • Often a prodrome 1 to 3 weeks prior to onset of lesions; can consist of malaise, fever, weight loss, cough, and arthralgia
  • Increasingly tender nodules on the legs, usually over the shins
  • Fever, malaise, chills, fatigue
  • Headache
  • Can precede systemic process by weeks

PHYSICAL EXAM

  • Lesions initially present as warm, tender, erythematous firm nodules and become fluctuant, gradually fading to resemble a bruise over 1 to 2 months (erythema contusiformis).
  • Typically pretibial, although can extend proximally to involve thighs or trunk (atypically can involve extensor surface of forearms)
  • Diameter varies from 1 to 10 cm with poor demarcation.

DIFFERENTIAL DIAGNOSIS

  • Nodular vasculitis or erythema induratum (warm ulcerating calf nodules)
  • Superficial thrombophlebitis
  • Cellulitis
  • Weber-Christian disease (violaceous, scarring nodules)
  • Lupus panniculitis
  • Cutaneous polyarteritis nodosa
  • Sarcoidal granulomas
  • Cutaneous T-cell lymphoma
  • EN leprosum (clinically similar to EN but shows vasculitis on histopathology)
  • Subcutaneous infection (including staphylococcus, Sporothrix schenckii, Nocardia brasiliensis, Mycobacterium marinum, Leishmania braziliensis)

DIAGNOSTIC TESTS & INTERPRETATION

  • ESR or C-reactive protein (CRP): often elevated, but can be normal in up to 40% (2)[C]
  • CBC: mild leukocytosis (2)[C]
  • Urine pregnancy test (2)[C]
  • Throat culture, antistreptolysin O titer (2)[C]
  • Blood and/or stool culture, stool ova and parasites (O&P)
  • Tuberculin skin testing (2)[C]
  • Seronegative rheumatoid factor
  • Septal panniculitis without vasculitis
  • Neutrophilic infiltrate in septa of fat tissue early in course
  • Actinic radial (Miescher) granulomas, consisting of collections of histocytes around a central stellate cleft, may be seen.
  • Fibrosis, paraseptal granulation tissue, lymphocytes, and multinucleated giant cells predominate late in course (4)

TREATMENT

  • Condition usually self-limited within 1 to 2 months
  • All medications listed as treatment for EN are off-label uses of the medications. There are no specific FDA-approved medications.

GENERAL MEASURES

  • Mild compression bandages and leg elevation may reduce pain. (Wet dressings, hot soaks, and topical medications are not useful.)
  • Discontinue potentially causative drugs.
  • Treat underlying disease.
  • Indication for treatment is poorly defined in literature; hence, therapy specifically for EN is directed towards symptom management.

MEDICATION

  • NSAIDs:Ibuprofen 400 mg PO q4-6h (not to exceed 3,200 mg/day)Indomethacin 25 to 50 mg PO TIDNaproxen 250 to 500 mg PO BID
  • PrecautionsGI upset/bleeding (avoid in Crohn or ulcerative colitis)Fluid retentionRenal insufficiencyDose reduction in elderly, especially those with renal disease, diabetes, or heart failureMay mask feverNSAIDs can increase cardiovascular (CV) risk.
  • Significant possible interactionsMay blunt antihypertensive effects of diuretics and β-blockersNSAIDs can elevate plasma lithium levels.NSAIDs can cause significant elevation and prolongation of methotrexate levels.
  • Ibuprofen 400 mg PO q4-6h (not to exceed 3,200 mg/day)
  • Indomethacin 25 to 50 mg PO TID
  • Naproxen 250 to 500 mg PO BID
  • GI upset/bleeding (avoid in Crohn or ulcerative colitis)
  • Fluid retention
  • Renal insufficiency
  • Dose reduction in elderly, especially those with renal disease, diabetes, or heart failure
  • May mask fever
  • NSAIDs can increase cardiovascular (CV) risk.
  • May blunt antihypertensive effects of diuretics and β-blockers
  • NSAIDs can elevate plasma lithium levels.
  • NSAIDs can cause significant elevation and prolongation of methotrexate levels.
  • Potassium iodide 400 to 900 mg/day divided BID or TID — 3 to 4 weeks (for persistent lesions); need to monitor for hyperthyroidism with prolonged use; pregnancy class D (5)[B]
  • Corticosteroids for severe, refractory, or recurrent cases in which an infectious workup is negative. Prednisone 1 mg/kg/day for 1 to 2 weeks is the recommended dose/duration. Potential side effects include hyperglycemia, hypertension, weight gain, worsening gastroesophageal reflux disease, mood changes, bone loss, osteonecrosis, and proximal myopathy (1)
  • For EN related to Beh §et disease, one can also consider colchicine 0.6 to 1.2 mg BID. Potential side effects include GI upset and diarrhea (6)[B].

INPATIENT CONSIDERATIONS

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

  • Keep legs elevated
  • Elastic wraps or support stockings may be helpful when patients are ambulating.

DIET

PATIENT EDUCATION

  • Lesions will resolve over a few weeks to months
  • Scarring is unlikely.
  • Joint aches and pains may persist.
  • <20% recur

PROGNOSIS

  • Individual lesions resolve generally within 2 weeks.
  • Total time course of 6 to 12 weeks but may vary with underlying disease.
  • Joint aches and pains may persist for years.
  • Lesions do not scar.
  • Recurrences: occurs over variable periods, averaging several years; seen most often in sarcoid, streptococcal infection, pregnancy, and oral contraceptive use. If medication induced, avoid recurrent exposure.

COMPLICATIONS

  • Vary according to underlying disease
  • None expected from lesions of EN

REFERENCES

ADDITIONAL READING

  • Bartyik K, V ¡rkonyi A, Kirschner A, et al. Erythema nodosum in association with celiac disease. Pediatr Dermatol. 2004;21(3):227-230.
  • Chong TA, Hansra NK, Ruben BS, et al. Diverticulitis: an inciting factor in erythema nodosum. J Am Acad Dermatol. 2012;67(1):e60-e62.
  • Harris T, Henderson MC. Concurrent Sweet's syndrome and erythema nodosum. J Gen Intern Med. 2011;26(2):214-215.
  • Jeon HC, Choi M, Paik SH, et al. A case of assisted reproductive therapy-induced erythema nodosum. Ann Dermatol. 2011;23(3):362-364.
  • Schwartz RA, Nervi SJ. Erythema nodosum: a sign of systemic disease. Am Fam Physician. 2007;75(5):695-700.
  • Then C, Langer A, Adam C, et al. Erythema nodosum associated with myelodysplastic syndrome: a case report. Onkologie. 2011;34(3):126-128.

CODES

ICD10

  • L52 Erythema nodosum
  • A18.4 Tuberculosis of skin and subcutaneous tissue

ICD9

  • 695.2 Erythema nodosum
  • 017.10 Erythema nodosum with hypersensitivity reaction in tuberculosis, unspecified

SNOMED

  • 32861005 Erythema nodosum (disorder)
  • 74610006 Tuberculous erythema nodosum (disorder)
  • 402969008 Erythema nodosum due to streptococcal infection (disorder)
  • 240411003 Erythema nodosum leprosum (disorder)
  • 297940005 Drug-induced erythema nodosum (disorder)
  • 240360007 Yersinia erythema nodosum (disorder)

CLINICAL PEARLS

  • Lesions of EN appear to be erythematous patches, but when palpated, their underlying nodularity is appreciated.
  • Evaluation for a concerning underlying etiology is necessary in EN, but most cases are idiopathic.
  • EN in the setting of hilar adenopathy may be seen with multiple etiologies and does not exclusively indicate sarcoidosis.
  • In patients with a history of Hodgkin lymphoma, EN may be an early sign of recurrence.