- Published on
Infectious Disease - Erythema Nodosum
ERYTHEMA NODOSUM
FUNDAMENTALS OVERVIEW
Erythema nodosum is the most prevalent form of panniculitis. The clinical presentation includes inflammatory, painful, nodular lesions. The lesions are predominantly situated on the lower limbs.
EPIDEMIOLOGY
Incidence • The highest incidence is observed between the ages of 18 and 34 years. The annual incidence rate of biopsy-confirmed erythema nodosum in hospitalized patients aged 14 years and older was estimated at 52 occurrences per million individuals. • Predominantly observed in females.
Prevalence • 2.4 cases per 1,000 individuals annually. • Seasonal aggregation of sarcoidosis presenting with erythema nodosum has also been documented. Clustering peaked in August, September, and October.
RISK FACTORS: Genetics Particular human leukocyte antigens, HLA-B8 and HLA-DR3, were identified as correlated with the occurrence of erythema nodosum in sarcoidosis.
PATHOPHYSIOLOGY
Erythema nodosum can be classified as a type IV delayed hypersensitivity reaction to many antigens.
CAUSES
Multiple etiological variables have been linked to erythema nodosum: Bacterial infections: Streptococcal infections (Group A beta-hemolytic Streptococcus) are the most prevalent infectious etiologies of erythema nodosum, along with mycobacterial infections (Hansen's bacillus, tuberculosis), brucellosis, cat-scratch disease, and Yersinia enterocolitica. Syphilis, along with infections caused by Salmonella spp. (S. enteritidis and S. typhi), Mycoplasma spp., Chlamydia spp. (including C. psittaci, C. pneumoniae, and C. trachomatis), Neisseria meningitidis, N. gonorrhoeae, Francisella tularensis, and Rickettsiae spp., may also induce erythema nodosum. • Viral infections: Cytomegalovirus (CMV), Epstein-Barr virus (EBV), Human Immunodeficiency Virus (HIV), Hepatitis B virus (HBV), Herpes Simplex Virus (HSV) • Fungal infections: Coccidioidomycosis, aspergillosis, histoplasmosis • Protozoal infections: Amebiasis, toxoplasmosis, giardiasis • Pharmacological agents: Sulphonamides, sulfones, bromides, oral contraceptives • Malignancies: Hodgkin’s disease, non-Hodgkin’s lymphoma, leukemia, pancreatic carcinoma, colon adenocarcinoma • Other pathological conditions: Sarcoidosis, Adamantiades–Behcet’s disease, Crohn’s disease, ulcerative colitis, Sweet’s syndrome, lupus erythematosus, Sjögren’s syndrome • Gestation • Idiopathic (likely the predominant etiology)
DIAGNOSIS HISTORY
• Diligent medical history acquisition is critically significant. • Abrupt emergence of painful, erythematous nodules and elevated plaques typically found on the shins, ankles, and knees. • Erythema nodosum frequently presents with fever ranging from approximately 38–39°C, along with exhaustion and joint pain. • Generally self-resolving within several weeks.
PHYSICAL EXAM • Erythematous, sensitive red nodules and elevated plaques situated on the shins, ankles, knees, and infrequently on the extensor surfaces of the arms, neck, or face. Initially, the nodules exhibit a vivid red hue and are elevated; however, within a few days, they flatten and assume a livid red or purplish tint. Ultimately, they transition to a yellow or greenish hue and frequently resemble a pronounced bruise (“erythema contusiformis”). The nodules resolve without atrophy or scarring. Ulceration is never noticed.
DIAGNOSTIC TESTS AND INTERPRETATION LAB • Complete blood count • Erythrocyte sedimentation rate • Antistreptolysin O titer • Rapid antigen test for streptococcus • Polymerase chain reaction for streptococcal DNA detection • Throat culture • Urinalysis • Intradermal tuberculin test Chest radiograph (tuberculosis, bilateral hilar lymphadenopathy [Lofgren’s syndrome])
Diagnostic Procedures and Additional Methods
• Evaluate stool culture and parasite examination if abdominal pain, bloating, or diarrhea is present. • Conduct a punch biopsy of the skin. • Perform a transbronchial lung biopsy for histological confirmation of sarcoidosis. • Execute a biopsy of the gastrocnemius muscle, as myopathy is frequently observed in Lofgren’s syndrome. • Administer an interferon-γ release assay. • Consider colonoscopy to exclude inflammatory bowel disease. Pathological Observations The histopathologic hallmark is the presence of "Miescher's radial granulomas." It comprises discrete, distinct nodular clusters of histiocytes surrounding a central cleft. Additionally, infiltration of polymorphonuclear leukocytes is another histopathological observation.
DIFFERENTIAL DIAGNOSIS • Erythema induratum of Bazin: – Histopathological distinctions: Erythema induratum of Bazin mostly presents as lobular panniculitis, in contrast to erythema nodosum, which predominantly exhibits septal panniculitis. The nodules of erythema induratum of Bazin are primarily situated on the posterior aspect of the legs, exhibit greater persistence, and may also present with ulceration. • Dermatological manifestations of superficial thrombophlebitis: The lesions are predominantly situated on the lateral aspects of the legs and present as firm, irregular, fibrotic cords or plaques. The biopsy indicates minimal to no signs of inflammatory infiltration, suggesting a vasculitic rather than a panniculitic disease. • Lyme disease • Etiologies of panniculitis (e.g., systemic lupus erythematosus [SLE], acute pancreatitis)
TREATMENT MEDICATION
Initial Line Erythema nodosum is predominantly self-limiting, resolving in most individuals within several weeks. Treatment must be tailored to the underlying condition. • Symptomatic management may involve nonsteroidal anti-inflammatory medications (NSAIDs): Indomethacin 100–150 mg daily, naproxen 500 mg daily. Avoid NSAIDs if the etiology is inflammatory bowel illness. • Steroids may be administered in severe situations when infectious etiologies or malignancies have been excluded. • Prednisone administered at a dosage of 1 mg/kg, gradually reduced over many days. • Potassium iodide: The maximum dosage for adults is 300 mg administered three times daily. Nonetheless, significant secondary hyperthyroidism may arise. • Hydroxychloroquine (specifically for persistent erythema nodosum; 200 mg bi-daily). Colchicine (effective for erythema nodosum linked to Adamantiades–Behcet’s illness; 1–2 mg daily, administered in two doses). Erythema nodosum leprosum: Evidence exists supporting the efficacy of thalidomide and clofazimine. Furthermore, a markedly reduced incidence of mild side events was observed with a low-dose thalidomide regimen in comparison to a high-dose regimen . Second Line: Infliximab is indicated for erythema nodosum linked to inflammatory bowel illness.
SUPPLEMENTARY THERAPY
General Measures: • Bed rest • Consistent elevation • Compression
CONTINUING TREATMENT OUTLOOK • Most cases cure within 3 to 4 weeks. • Recurrence is infrequent, however more prevalent in idiopathic cases of erythema nodosum and in those associated with upper respiratory tract infections (either streptococcal or non-streptococcal).
COMPLICATIONS • Optic nerve neuritis has been documented in a patient during an acute episode of erythema nodosum.
ERYTHEMA NODOSUM
FUNDAMENTALS OVERVIEW
Erythema nodosum is the most prevalent form of panniculitis. The clinical presentation includes inflammatory, painful, nodular lesions. The lesions are predominantly situated on the lower limbs.
EPIDEMIOLOGY
Incidence • The highest incidence is observed between the ages of 18 and 34 years. The annual incidence rate of biopsy-confirmed erythema nodosum in hospitalized patients aged 14 years and older was estimated at 52 occurrences per million individuals. • Predominantly observed in females.
Prevalence • 2.4 cases per 1,000 individuals annually. • Seasonal aggregation of sarcoidosis presenting with erythema nodosum has also been documented. Clustering peaked in August, September, and October.
RISK FACTORS: Genetics Particular human leukocyte antigens, HLA-B8 and HLA-DR3, were identified as correlated with the occurrence of erythema nodosum in sarcoidosis.
PATHOPHYSIOLOGY
Erythema nodosum can be classified as a type IV delayed hypersensitivity reaction to many antigens.
CAUSES
Multiple etiological variables have been linked to erythema nodosum: Bacterial infections: Streptococcal infections (Group A beta-hemolytic Streptococcus) are the most prevalent infectious etiologies of erythema nodosum, along with mycobacterial infections (Hansen's bacillus, tuberculosis), brucellosis, cat-scratch disease, and Yersinia enterocolitica. Syphilis, along with infections caused by Salmonella spp. (S. enteritidis and S. typhi), Mycoplasma spp., Chlamydia spp. (including C. psittaci, C. pneumoniae, and C. trachomatis), Neisseria meningitidis, N. gonorrhoeae, Francisella tularensis, and Rickettsiae spp., may also induce erythema nodosum. • Viral infections: Cytomegalovirus (CMV), Epstein-Barr virus (EBV), Human Immunodeficiency Virus (HIV), Hepatitis B virus (HBV), Herpes Simplex Virus (HSV) • Fungal infections: Coccidioidomycosis, aspergillosis, histoplasmosis • Protozoal infections: Amebiasis, toxoplasmosis, giardiasis • Pharmacological agents: Sulphonamides, sulfones, bromides, oral contraceptives • Malignancies: Hodgkin’s disease, non-Hodgkin’s lymphoma, leukemia, pancreatic carcinoma, colon adenocarcinoma • Other pathological conditions: Sarcoidosis, Adamantiades–Behcet’s disease, Crohn’s disease, ulcerative colitis, Sweet’s syndrome, lupus erythematosus, Sjögren’s syndrome • Gestation • Idiopathic (likely the predominant etiology)
DIAGNOSIS HISTORY
• Diligent medical history acquisition is critically significant. • Abrupt emergence of painful, erythematous nodules and elevated plaques typically found on the shins, ankles, and knees. • Erythema nodosum frequently presents with fever ranging from approximately 38–39°C, along with exhaustion and joint pain. • Generally self-resolving within several weeks.
PHYSICAL EXAM • Erythematous, sensitive red nodules and elevated plaques situated on the shins, ankles, knees, and infrequently on the extensor surfaces of the arms, neck, or face. Initially, the nodules exhibit a vivid red hue and are elevated; however, within a few days, they flatten and assume a livid red or purplish tint. Ultimately, they transition to a yellow or greenish hue and frequently resemble a pronounced bruise (“erythema contusiformis”). The nodules resolve without atrophy or scarring. Ulceration is never noticed.
DIAGNOSTIC TESTS AND INTERPRETATION LAB • Complete blood count • Erythrocyte sedimentation rate • Antistreptolysin O titer • Rapid antigen test for streptococcus • Polymerase chain reaction for streptococcal DNA detection • Throat culture • Urinalysis • Intradermal tuberculin test Chest radiograph (tuberculosis, bilateral hilar lymphadenopathy [Lofgren’s syndrome])
Diagnostic Procedures and Additional Methods
• Evaluate stool culture and parasite examination if abdominal pain, bloating, or diarrhea is present. • Conduct a punch biopsy of the skin. • Perform a transbronchial lung biopsy for histological confirmation of sarcoidosis. • Execute a biopsy of the gastrocnemius muscle, as myopathy is frequently observed in Lofgren’s syndrome. • Administer an interferon-γ release assay. • Consider colonoscopy to exclude inflammatory bowel disease. Pathological Observations The histopathologic hallmark is the presence of "Miescher's radial granulomas." It comprises discrete, distinct nodular clusters of histiocytes surrounding a central cleft. Additionally, infiltration of polymorphonuclear leukocytes is another histopathological observation.
DIFFERENTIAL DIAGNOSIS • Erythema induratum of Bazin: – Histopathological distinctions: Erythema induratum of Bazin mostly presents as lobular panniculitis, in contrast to erythema nodosum, which predominantly exhibits septal panniculitis. The nodules of erythema induratum of Bazin are primarily situated on the posterior aspect of the legs, exhibit greater persistence, and may also present with ulceration. • Dermatological manifestations of superficial thrombophlebitis: The lesions are predominantly situated on the lateral aspects of the legs and present as firm, irregular, fibrotic cords or plaques. The biopsy indicates minimal to no signs of inflammatory infiltration, suggesting a vasculitic rather than a panniculitic disease. • Lyme disease • Etiologies of panniculitis (e.g., systemic lupus erythematosus [SLE], acute pancreatitis)
TREATMENT MEDICATION
Initial Line Erythema nodosum is predominantly self-limiting, resolving in most individuals within several weeks. Treatment must be tailored to the underlying condition. • Symptomatic management may involve nonsteroidal anti-inflammatory medications (NSAIDs): Indomethacin 100–150 mg daily, naproxen 500 mg daily. Avoid NSAIDs if the etiology is inflammatory bowel illness. • Steroids may be administered in severe situations when infectious etiologies or malignancies have been excluded. • Prednisone administered at a dosage of 1 mg/kg, gradually reduced over many days. • Potassium iodide: The maximum dosage for adults is 300 mg administered three times daily. Nonetheless, significant secondary hyperthyroidism may arise. • Hydroxychloroquine (specifically for persistent erythema nodosum; 200 mg bi-daily). Colchicine (effective for erythema nodosum linked to Adamantiades–Behcet’s illness; 1–2 mg daily, administered in two doses). Erythema nodosum leprosum: Evidence exists supporting the efficacy of thalidomide and clofazimine. Furthermore, a markedly reduced incidence of mild side events was observed with a low-dose thalidomide regimen in comparison to a high-dose regimen . Second Line: Infliximab is indicated for erythema nodosum linked to inflammatory bowel illness.
SUPPLEMENTARY THERAPY
General Measures: • Bed rest • Consistent elevation • Compression
CONTINUING TREATMENT OUTLOOK • Most cases cure within 3 to 4 weeks. • Recurrence is infrequent, however more prevalent in idiopathic cases of erythema nodosum and in those associated with upper respiratory tract infections (either streptococcal or non-streptococcal).
COMPLICATIONS • Optic nerve neuritis has been documented in a patient during an acute episode of erythema nodosum.
0 Comments
