Erythema Nodosum - Causes, Clinical Presentation, Diagnosis, and Treatment

Introduction

Erythema nodosum (EN) is a type of skin inflammation characterized by an acute, nodular, red, inflamed eruption on the fatty layer of skin. It is assumed to be a hypersensitivity reaction associated with some systemic conditions, drug therapies, or idiopathic. The inflammatory response follows panniculus. In chronic erythema nodosum, the lesions pop up in different places for weeks to months. However, it may even last for years in another pattern. Chronic erythema nodosum, with a chance of recurrence, can appear with or without an underlying disease.

What Causes Erythema Nodosum?

Erythema nodosum can occur with various underlying infectious and non-infectious conditions. Sometimes, the cause of erythema nodosum remains unknown. As erythema nodosum is a hypersensitivity reaction, about 30 percent to 50 percent of the patients do not have any underlying disease, and the cause remains unknown.

Infectious causes are as follows:

1) Bacterial Infection:

• Streptococcal infection causes streptococcal pharyngitis, which is a common cause.

• Leprosy.

• Tuberculosis.

• Salmonella, Yersinia, Campylobacter gastroenteritis.

• Tularemia.

• Mycoplasma pneumonia.

• Cat scratch disease (Bartonella species).

• Brucellosis.

• Leptospirosis.

• Psittacosis.

• Lymphogranuloma venereum.

• Chlamydia trachomatis.

2) Viral Infection:

• Hepatitis B and Hepatitis C.

• Infectious mononucleosis.

• Human immunodeficiency virus (HIV).

• Epstein-Barr virus (EBV).

• Herpes simplex virus (HSV).

• Para vaccinia.

3) Fungal Infection:

• Coccidioidomycosis.

• Blastomycosis.

• Histoplasmosis.

4) Parasitic Infection:

• Amebiasis.

• Giardiasis.

Non-infectious causes:

1) Drugs:

• Antibiotics - Sulfonamides, Penicillins.

• Miscellaneous drugs - Oral contraceptives, Bromides, Iodides, TNF-alpha inhibitor, Non-steroidal anti-inflammatory drugs, Gold salt, Salicylates.

2) Malignancy:

• Lymphoma.

• Leukemia.

• Occult malignancies.

3) Inflammatory Bowel Disease:

• Ulcerative colitis.

• Crohn disease.

4) Miscellaneous:

• Lofgren syndrome (acute sarcoidosis with a triad of erythema nodosum, polyarthritis, and hilar lymphadenopathy).

• Pregnancy (during the second trimester).

• Behcet’s syndrome.

• Whipple disease.

What Is the Pathophysiology of Erythema Nodosum?

A nonspecific cutaneous reaction to different antigens causes erythema nodosum. It would be an immunologically mediated mechanism. The idea of a type IV delayed hypersensitivity response to several antigens is supported by a wealth of direct and indirect evidence. Pathogenesis is thought to be caused by immune complexes depositing in subcutaneous fat venules, oxygen-free radical creation, TNF-alpha production, and granuloma formation.

Who Is Affected by Erythema Nodosum?

Erythema nodosum is more common in females between 25 and 40 years of age. Both men and women show equal predilection before puberty. Ethnicity, geographical differences, and familial inheritance have triggered the etiological factors.

What Happens in Erythema Nodosum?

Erythema nodosum is a delayed hypersensitivity reaction that affects a nonspecific skin reaction to different antigens. It is an immune-mediated skin reaction where the immune complexes are deposited in the subcutaneous fat venules, producing oxygen free radicals, tumor necrosis factor (TNF-alpha), and granuloma formation.

What Are the Clinical Presentations of Erythema Nodosum?

Erythema nodosum evolves over the period in its clinical presentation as follows:

• Prodromal Phase: The prodromal phase lasts three to six days and is characterized by fever, joint pain, and abdominal pain. It is associated with nasopharyngeal infection and slight changes in general health conditions.

• Stade Phase: The stade phase settles in one or two days and presents with fever, and arthralgia of the prodromal phase continues or increases. A few small, symmetrical, spontaneously painful nodules appear on the extremities of the legs, knees, thighs, and forearms. These nodules are ten to 40 mm in width, mobile, warm, and firm on palpation, resembling a knot. The pain is exacerbated when standing erect. It is accompanied by ankle swelling and hilar adenopathy (characteristic of sarcoidosis).

• Regressive Phase: Each nodule develops as a blue and yellowish hue in ten days that ruptures and completely fades without sequelae. Erythema nodosum does not cause ulceration, permanent scarring, or necrosis. Other most common symptoms of erythema nodosum are joint and muscle pain, morning stiffness and joint swelling, fever, and swollen lymph nodes in the chest.

How Is Erythema Nodosum Diagnosed?

Primary diagnosis of erythema nodosum involves:

• A thorough physical examination.

• A complete history of fever, dysentery, abdominal pain, tuberculous contagion, respiratory problems, and dysphagia should be taken.

• A laboratory and histopathologic investigation usually confirms the lesion.

Other Supporting Investigations Are:

• Complete and differential blood count and C-reactive protein are analyzed if any infection is suspected.

• A Mantoux test, chest X-ray, and interferon-gamma blood test are advised when tuberculosis or Lofgren syndrome is suspected.

• A throat smear culture and rapid serology test, namely anti-streptolysin O and streptodornase, are advised when a streptococcal infection is suspected.

• Two samples of viral serology at four-week intervals are advised when virosis is suspected.

• Stool examination when a history of diarrhea or digestive symptoms is present.

• Cutaneous biopsies, such as excisional or deep incisional skin biopsies, are done in atypical or doubtful cases.

How Is Erythema Nodosum Treated?

• Treatment of erythema nodosum is customized for every patient based on their symptoms. Hence, primary management includes simultaneously identifying and treating the underlying condition with the skin lesions.

• Sometimes, when no underlying cause is diagnosed, the lesion completely resolves in four to six weeks.

• Take enough bed rest to reduce pain and swelling.

• Pain medicines like Ibuprofen may be prescribed if necessary. In addition, venous compression may reduce the pain felt when in an erect standing position.

• Orally or injected anti-inflammatory drugs and cortisone. Colchicine may also be used to reduce inflammation effectively. Injections may be administered for large, painful nodules.

• Antibiotic therapy may be needed with a streptococcal infection or anti-tuberculosis treatment.

What Are the Lesions That Resemble Erythema Nodosum?

Various conditions resemble erythema nodosum.

They are:

• Infectious dermo hypodermitis.

• Periarteritis nodosa and superficial thrombophlebitis.

• Various forms of scleroderma.

• Necrobiosis lipoidica.

• Eosinophilic panniculitis.

• Rheumatoid nodule.

• Cutaneous lupus erythematosus.

• Erythema nodosum leprosum.

• Pancreatic panniculitis.

• Traumatic panniculitis.

• Nodular vasculitis (erythema induratum).

• Lipodermatosclerosis.

• Bacterial, mycobacterial, and fungal infection of the subcutaneous fat.

• Malignant infiltration.

How About the Prevention of Erythema Nodosum?

Erythema nodosum cannot be prevented, but certain steps can be followed to prevent the flare-up of the symptoms.

• Stay away from sick people.

• Avoid medications that promote the disease.

• Refrain from foods that cause diarrhea and loose stools (Irritable bowel Disease).

• Eat a well-balanced diet.

What Is the Prognosis of Erythema Nodosum?

The prognosis of erythema nodosum is usually good. However, one-third of erythema nodosum patients relapse to a chronic or persistent condition lasting six months and sometimes for years. There is no scarring or pigmentation change when the lesion heals.

What Are the Complications of Erythema Nodosum?

The complications of erythema nodosum usually resolve spontaneously. Rarely, mobile encapsulated lipoma or encapsulated fat necrosis.

Conclusion

Erythema nodosum, the most common type of panniculitis, is a painful subcutaneous fat disorder. Generally, it is idiopathic but is also a manifestation of underlying diseases or a reaction to a drug. It is a delayed hypersensitivity response to several antigens. Management is symptom-specific, and treating any underlying disorders present can resolve the lesion.