Erythema Nodosum

Epidemiology and Etiology

Epidemiology:

• Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion nodosum (EN) is most common in women in their 2nd–4th decades.
• Women are affected 3–6 times more often than men. 
• All ages and racial groups can be affected.
• Most common form of panniculitis ( inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of subcutaneous fat)

Etiology:

• Half of cases have an unknown etiology.
• Infection is the most commonly identified cause, especially streptococcal infection, but other bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology, as well as fungi Fungi A kingdom of eukaryotic, heterotrophic organisms that live parasitically as saprobes, including mushrooms; yeasts; smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi, commonly known as molds, refer to those that grow as multicellular colonies. Mycology and viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology, are known etiologic agents, including coronavirus disease 2019 Coronavirus disease 2019 Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly affects the respiratory system but can also cause damage to other body systems (cardiovascular, gastrointestinal, renal, and central nervous systems). ( COVID-19 COVID-19 Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly affects the respiratory system but can also cause damage to other body systems (cardiovascular, gastrointestinal, renal, and central nervous systems). ) (rare).
• Drugs: oral contraceptives, penicillin Penicillin Rheumatic Fever, sulfonamides Sulfonamides A group of compounds that contain the structure so2nh2. Sulfonamides and Trimethoprim, others
• Inflammatory bowel disease
• Malignancy Malignancy Hemothorax: hematologic malignancies and carcinoma
• Miscellaneous: pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care, sarcoidosis Sarcoidosis Sarcoidosis is a multisystem inflammatory disease that causes noncaseating granulomas. The exact etiology is unknown. Sarcoidosis usually affects the lungs and thoracic lymph nodes, but it can also affect almost every system in the body, including the skin, heart, and eyes, most commonly. Sarcoidosis, others

Pathophysiology

An immune-mediated reaction to various antigens results in subcutaneous fat inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation.

• Type IV hypersensitivity reaction Type IV hypersensitivity reaction Type IV hypersensitivity reaction, or delayed-type hypersensitivity, is a cell-mediated response to antigen exposure. The reaction involves T cells, not antibodies, and develops over several days. Presensitized T cells initiate the immune defense, leading to tissue damage. Type IV Hypersensitivity Reaction ( delayed-type hypersensitivity Delayed-type hypersensitivity Type IV hypersensitivity reaction, or delayed-type hypersensitivity, is a cell-mediated response to antigen exposure. The reaction involves T cells, not antibodies, and develops over several days. Presensitized T cells initiate the immune defense, leading to tissue damage. Type IV Hypersensitivity Reaction) to various antigens is considered to be the main immunologic mechanism, but other pathways may be involved, including immune complex deposition in subcutaneous fat.
• Causes erythematous, tender nodules, typically on the shins, but other areas may be involved
• Histology shows septal panniculitis without primary vasculitis, a mixed inflammatory infiltrate including eosinophils, Meischer’s “radial” granulomas Granulomas A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. Sarcoidosis in the early stages (such as histiocyte aggregates surrounding extracellular clefts with neutrophils Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. Innate Immunity: Phagocytes and Antigen Presentation at the periphery), and multinucleated giant cells Giant cells Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In aids, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. Giant Cell Arteritis in the later stages. Secondary vasculitis Vasculitis Inflammation of any one of the blood vessels, including the arteries; veins; and rest of the vasculature system in the body. Systemic Lupus Erythematosus may be seen if there are dense neutrophil infiltrates.

Clinical Presentation

• Prodromal symptoms may precede the eruption of skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions lesions and include:
  • Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia
  • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
  • Malaise Malaise Tick-borne Encephalitis Virus
  • Arthralgia Arthralgia Pain in the joint. Rheumatic Fever/ arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis 
• Characteristic skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions lesions:
  • Erythematous, tender nodules on both shins
    • Nonulcerated
    • Immobile
    • Slightly raised
    • Typically 2–5 cm
  • Develop over several days
    • Usually self-resolve without scarring Scarring Inflammation within 8 weeks of presentation
    • Bruising or residual hyperpigmentation Hyperpigmentation Excessive pigmentation of the skin, usually as a result of increased epidermal or dermal melanin pigmentation, hypermelanosis. Hyperpigmentation can be localized or generalized. The condition may arise from exposure to light, chemicals or other substances, or from a primary metabolic imbalance. Malassezia Fungi may occur during resolution.
  • Less common sites of nodules:
    • Ankles
    • Thighs
    • Buttocks
    • Calves
    • Face

Diagnosis and Management

Diagnosis

• Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion nodosum is usually diagnosed clinically by history and physical examination.
  • An acute onset of tender nonulcerated nodules or plaques on both shins is typical.
  • Skin biopsy Skin Biopsy Secondary Skin Lesions should be reserved for confirming the diagnosis if there are atypical lesions or the patient is immunosuppressed.
• Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship should be evaluated for underlying disease.
  • Thorough history and physical examination should include:
    • Medication history
    • Travel history
    • Review of respiratory, gastrointestinal, and constitutional symptoms Constitutional Symptoms Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis
    • Examination of the throat Throat The pharynx is a component of the digestive system that lies posterior to the nasal cavity, oral cavity, and larynx. The pharynx can be divided into the oropharynx, nasopharynx, and laryngopharynx. Pharyngeal muscles play an integral role in vital processes such as breathing, swallowing, and speaking. Pharynx: Anatomy and tonsils Tonsils Tonsillitis (to rule out streptococcal infection)
  • Laboratory workup may include:
    • CBC
    • Erythrocyte sedimentation rate Erythrocyte Sedimentation Rate Soft Tissue Abscess ( ESR ESR Soft Tissue Abscess) and/or C-reactive protein (CRP)
    • Throat Throat The pharynx is a component of the digestive system that lies posterior to the nasal cavity, oral cavity, and larynx. The pharynx can be divided into the oropharynx, nasopharynx, and laryngopharynx. Pharyngeal muscles play an integral role in vital processes such as breathing, swallowing, and speaking. Pharynx: Anatomy culture and antistreptolysin-O (ASO) titers 
    • Tuberculin Tuberculin A protein extracted from boiled culture of tubercle bacilli (Mycobacterium tuberculosis). It is used in the tuberculin skin test (tuberculin test) for the diagnosis of tuberculosis infection in asymptomatic persons. Type IV Hypersensitivity Reaction skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions test/interferon-gamma release assay 
    • Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care test
  • Imaging may include chest radiographs.

Management

• Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion nodosum is self-limiting Self-Limiting Meningitis in Children and usually resolves within 8 weeks.
  • Symptomatic treatment includes:
    • Rest and leg Leg The lower leg, or just “leg” in anatomical terms, is the part of the lower limb between the knee and the ankle joint. The bony structure is composed of the tibia and fibula bones, and the muscles of the leg are grouped into the anterior, lateral, and posterior compartments by extensions of fascia. Leg: Anatomy elevation
    • Venous compression Compression Blunt Chest Trauma by stocking (if tolerated)
    • Analgesics, such as nonsteroidal anti-inflammatory drugs ( NSAIDs NSAIDS Primary vs Secondary Headaches)
    • Potassium iodide Potassium iodide An inorganic compound that is used as a source of iodine in thyrotoxic crisis and in the preparation of thyrotoxic patients for thyroidectomy. Antithyroid Drugs (inhibits neutrophil chemotaxis Chemotaxis The movement of leukocytes in response to a chemical concentration gradient or to products formed in an immunologic reaction. Leukocyte Adhesion Deficiency Type 1 and generation of reactive oxygen species Reactive oxygen species Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include singlet oxygen; superoxides; peroxides; hydroxyl radical; and hypochlorous acid. They contribute to the microbicidal activity of phagocytes, regulation of signal transduction and gene expression, and the oxidative damage to nucleic acids; proteins; and lipids. Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD))
    • If infectious causes can be ruled out, systemic glucocorticoid therapy ( prednisone Prednisone A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. Immunosuppressants 20 mg/day for 7–10 days) can improve both pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and the appearance of erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion nodosum.
• The underlying causes should also be identified and treated.

Differential Diagnosis

• Nodular vasculitis Vasculitis Inflammation of any one of the blood vessels, including the arteries; veins; and rest of the vasculature system in the body. Systemic Lupus Erythematosus: a lobular panniculitis frequently associated with tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis. Often occurs on the posterior calves with ulcerated, draining nodules. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship would be expected to have a positive tuberculin Tuberculin A protein extracted from boiled culture of tubercle bacilli (Mycobacterium tuberculosis). It is used in the tuberculin skin test (tuberculin test) for the diagnosis of tuberculosis infection in asymptomatic persons. Type IV Hypersensitivity Reaction skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions test.
• Subcutaneous infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease: may be due to a bacterial, fungal, or mycobacterial infection. Often occurs on the legs/feet with fluctuant Fluctuant Dermatologic Examination, ulcerated, draining lesions. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship would be expected to have systemic signs of infection.
• Cutaneous polyarteritis nodosa Polyarteritis nodosa A form of necrotizing non-granulomatous inflammation occurring primarily in medium-sized arteries, often with microaneurysms. It is characterized by muscle, joint, and abdominal pain resulting from arterial infarction and scarring in affected organs. Polyarteritis nodosa with lung involvement is called churg-strauss syndrome. Vasculitides: characterized by painful subcutaneous nodules on the legs. However, these nodules are also associated with livedo racemosa, necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage, and ulcerations. Histology shows segmental necrotizing medium artery vasculitis Vasculitis Inflammation of any one of the blood vessels, including the arteries; veins; and rest of the vasculature system in the body. Systemic Lupus Erythematosus. 
• Pancreatic panniculitis: These nodules differ in that they are fluctuant Fluctuant Dermatologic Examination and ulcerative with oily fluid drainage. They often heal with scarring Scarring Inflammation. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship would be expected to have symptoms of pancreatitis Pancreatitis Inflammation of the pancreas. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of chronic pancreatitis. The two most common forms of acute pancreatitis are alcoholic pancreatitis and gallstone pancreatitis. Acute Pancreatitis including fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever and abdominal pain Abdominal Pain Acute Abdomen. Laboratory results would reveal elevated lipase Lipase An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. Malabsorption and Maldigestion and amylase Amylase A group of amylolytic enzymes that cleave starch, glycogen, and related alpha-1, 4-glucans. Digestion and Absorption.
• Alpha-1 antitrypsin Alpha-1 antitrypsin Plasma glycoprotein member of the serpin superfamily which inhibits trypsin; neutrophil elastase; and other proteolytic enzymes. Alpha-1 Antitrypsin (AAT) Deficiency deficiency: This genetic defect Genetic Defect Ion Channel Myopathy may be associated with subcutaneous nodules or plaques that frequently ulcerate and drain. 
  

Clinical Relevance

• EN can offer clues to the presence of a serious underlying treatable disease, such as streptococcal infection, sarcoidosis Sarcoidosis Sarcoidosis is a multisystem inflammatory disease that causes noncaseating granulomas. The exact etiology is unknown. Sarcoidosis usually affects the lungs and thoracic lymph nodes, but it can also affect almost every system in the body, including the skin, heart, and eyes, most commonly. Sarcoidosis, tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis, and coccidioidomycosis Coccidioidomycosis Coccidioidomycosis, commonly known as San Joaquin Valley fever, is a fungal disease caused by Coccidioides immitis or Coccidioides posadasii. When Coccidioides spores are inhaled, they transform into spherules that result in infection. Coccidioidomycosis is also a common cause of community-acquired pneumonia and can cause severe disease in the immunocompromised. Coccidioides/Coccidioidomycosis.
• EN may have prognostic value in a few situations because it is associated with the following:
  • A lower incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of disseminated disease in coccidioidomycosis Coccidioidomycosis Coccidioidomycosis, commonly known as San Joaquin Valley fever, is a fungal disease caused by Coccidioides immitis or Coccidioides posadasii. When Coccidioides spores are inhaled, they transform into spherules that result in infection. Coccidioidomycosis is also a common cause of community-acquired pneumonia and can cause severe disease in the immunocompromised. Coccidioides/Coccidioidomycosis
  • A less aggressive form of sarcoidosis Sarcoidosis Sarcoidosis is a multisystem inflammatory disease that causes noncaseating granulomas. The exact etiology is unknown. Sarcoidosis usually affects the lungs and thoracic lymph nodes, but it can also affect almost every system in the body, including the skin, heart, and eyes, most commonly. Sarcoidosis (Lofgren syndrome triad of EN, hilar lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy, and acute arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis/periarthritis)
• EN may precede or be coincident with an acute flare of inflammatory bowel disease