Erythema Nodosum (Clinical)

Epidemiology and Etiology

Epidemiology^[1‒4]

• 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 EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum) 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 Panniculitis General term for inflammation of adipose tissue, usually of the skin, characterized by reddened subcutaneous nodules. Erythema Nodosum ( 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 Subcutaneous fat Fatty tissue under the skin throughout the body. Erythema Nodosum)
• 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 has decreased with the use of antibiotics to approximately 1‒5 per 100,000

Etiology^[2‒6]

• Half of cases have an unknown etiology ( idiopathic Idiopathic Dermatomyositis).
• 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:
  • Streptococcal 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 (the most commonly identified etiology)
  • 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, 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, 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 parasites
• 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 Subcutaneous fat Fatty tissue under the skin throughout the body. Erythema Nodosum 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 (septal panniculitis Panniculitis General term for inflammation of adipose tissue, usually of the skin, characterized by reddened subcutaneous nodules. Erythema Nodosum).^[1‒3]

• 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.
• Other pathways may be involved, including immune complex deposition in subcutaneous fat Subcutaneous fat Fatty tissue under the skin throughout the body. Erythema Nodosum.
• Often occurs in association with granulomatous disease Granulomatous disease A defect of leukocyte function in which phagocytic cells ingest but fail to digest bacteria, resulting in recurring bacterial infections with granuloma formation. When chronic granulomatous disease is caused by mutations in the cybb gene, the condition is inherited in an X-linked recessive pattern. When chronic granulomatous disease is caused by cyba, ncf1, ncf2, or ncf4 gene mutations, the condition is inherited in an autosomal recessive pattern. Common Variable Immunodeficiency (CVID) (e.g., 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, TB TB 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)
• Expression of adhesion Adhesion The process whereby platelets adhere to something other than platelets, e.g., collagen; basement membrane; microfibrils; or other ‘foreign’ surfaces. Coagulation Studies molecules and inflammatory mediators, including high levels of cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response and growth factors, in both 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 and serum
• Causes erythematous, tender nodules, typically on the shins Shins Erythema Nodosum, but other areas may be involved

Clinical Presentation

Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may present with:^[1,2,5,7]

• 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 Shins Erythema Nodosum
    • 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 Calves Erythema Nodosum
    • Forearms Forearms Part of the upper extremity in humans and primates extending from the elbow to the wrist. Bowen Disease and Erythroplasia of Queyrat
    • Face

Diagnosis and Management

Diagnostic and management criteria may vary depending on practice location. The following information on diagnosis and management is based on US and UK medical society recommendations.

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. Acute onset of tender nonulcerated nodules or plaques on both shins Shins Erythema Nodosum is typical. 

Skin biopsy Skin Biopsy Secondary Skin Lesions:^[1‒3,5]

• Reserved for confirming the diagnosis when:
  • There are atypical lesions or a nonclassic presentation
  • Patient is immunosuppressed
• Obtaining the biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma:
  • Should be either a deep incisional or excisional biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma
  • Include a generous portion of subcutaneous fat Subcutaneous fat Fatty tissue under the skin throughout the body. Erythema Nodosum
• Histology shows:^[1,7]
  • Septal panniculitis Panniculitis General term for inflammation of adipose tissue, usually of the skin, characterized by reddened subcutaneous nodules. Erythema Nodosum without primary 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 mixed inflammatory infiltrate including eosinophils Eosinophils Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. Innate Immunity: Phagocytes and Antigen Presentation
  • Miescher’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)
  • 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 neutrophilic infiltrates.

Evaluate for an underlying cause:^[1‒3,5,7]

• 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:
    • Neutrophilia/increased bands → bacterial infection
    • Atypical lymphocytosis Lymphocytosis WBCs develop from stem cells in the bone marrow and are called leukocytes when circulating in the bloodstream. Lymphocytes are 1 of the 5 subclasses of WBCs. Lymphocytosis is an increase in the number or proportion of the lymphocyte subclass of WBCs, often as a result of an immune response to infection (known as reactive lymphocytosis). Lymphocytosis → mononucleosis Mononucleosis Infectious mononucleosis (IM), also known as “the kissing disease,” is a highly contagious viral infection caused by the Epstein-Barr virus. Its common name is derived from its main method of transmission: the spread of infected saliva via kissing. Clinical manifestations of IM include fever, tonsillar pharyngitis, and lymphadenopathy. Mononucleosis
    • Eosinophilia Eosinophilia Abnormal increase of eosinophils in the blood, tissues or organs. Autosomal Dominant Hyperimmunoglobulin E Syndrome → allergic disease, chlamydial and parasitic 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
    • Pancytopenia Pancytopenia Deficiency of all three cell elements of the blood, erythrocytes, leukocytes and platelets. Aplastic Anemia or leukocytosis Leukocytosis A transient increase in the number of leukocytes in a body fluid. West Nile Virus → leukemia
  • Erythrocyte sedimentation rate Erythrocyte Sedimentation Rate Soft Tissue Abscess ( ESR ESR Soft Tissue Abscess) and/or C-reactive protein (CRP) → elevated levels potentially suggest:
    • Widespread 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
    • Systemic disease
    • Active bacterial infection
  • 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 Antistreptolysin Antibodies specific to streptolysins which indicate streptococcal infections. Postinfectious Glomerulonephritis O (ASO) titers to rule out streptococcal infection
  • 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 
  • Stool exam:
    • Consider a stool culture and ova and parasite test if there are GI symptoms (e.g., diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea).
    • Consider evaluation for inflammatory bowel disease.
  • 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, which may show evidence 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 (e.g., bilateral 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)
  • 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 (e.g., unilateral 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
  • Other pulmonary 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
  • Lymphoma Lymphoma A general term for various neoplastic diseases of the lymphoid tissue. Imaging of the Mediastinum

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:^[1‒4,7]

• 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)
  • First-line drugs for pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways control
  • Potential options:
    • Ibuprofen Ibuprofen A nonsteroidal anti-inflammatory agent with analgesic properties used in the treatment of rheumatism and arthritis. Nonsteroidal Antiinflammatory Drugs (NSAIDs)
    • Naproxen Naproxen An anti-inflammatory agent with analgesic and antipyretic properties. Both the acid and its sodium salt are used in the treatment of rheumatoid arthritis and other rheumatic or musculoskeletal disorders, dysmenorrhea, and acute gout. Nonsteroidal Antiinflammatory Drugs (NSAIDs)
    • Indomethacin Indomethacin A non-steroidal anti-inflammatory agent (nsaid) that inhibits cyclooxygenase, which is necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. Nonsteroidal Antiinflammatory Drugs (NSAIDs)
• 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. Nonalcoholic Fatty Liver Disease
  • Dosing:
    • Initial: 300‒900 mg daily^[1,7]
    • Tapered to 150 mg/day^[1]
    • Optimal duration is unclear.
  • Use with caution in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy disease
  • Contraindicated in 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 or in those who are breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding^[1]

Antiinflammatory medications:^[1,7]

• Used in cases of severe, recurrent, and/or recalcitrant disease to improve pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and/or appearance of lesions
• Specialty consultation should be considered in cases requiring additional medical therapy.
• 2nd-line option: corticosteroids Corticosteroids Chorioretinitis
  • Systemic: prednisone Prednisone A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. Immunosuppressants 20‒60 mg daily for 7‒10 days, followed by a taper
  • Intralesional: triamcinolone Triamcinolone A glucocorticoid given, as the free alcohol or in esterified form, orally, intramuscularly, by local injection, by inhalation, or applied topically in the management of various disorders in which corticosteroids are indicated. Glucocorticoids acetonide 5 mg/mL
  • Ensure that underlying infection (e.g., TB TB 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) has been ruled out.
• Additional options:
  • Tetracyclines Tetracyclines Tetracyclines are a class of broad-spectrum antibiotics indicated for a wide variety of bacterial infections. These medications bind the 30S ribosomal subunit to inhibit protein synthesis of bacteria. Tetracyclines cover gram-positive and gram-negative organisms, as well as atypical bacteria such as chlamydia, mycoplasma, spirochetes, and even protozoa. Tetracyclines:
    • Minocycline Minocycline A tetracycline analog, having a 7-dimethylamino and lacking the 5 methyl and hydroxyl groups, which is effective against tetracycline-resistant staphylococcus infections. Tetracyclines 100 mg twice daily
    • Tetracycline Tetracycline A naphthacene antibiotic that inhibits amino Acyl tRNA binding during protein synthesis. Drug-Induced Liver Injury 500 mg 2–4 times daily
    • Doxycycline 100 mg daily
  • Erythromycin Erythromycin A bacteriostatic antibiotic macrolide produced by streptomyces erythreus. Erythromycin a is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50s ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. Macrolides and Ketolides 500 mg 4 times daily
  • Dapsone Dapsone A sulfone active against a wide range of bacteria but mainly employed for its actions against Mycobacterium leprae. Its mechanism of action is probably similar to that of the sulfonamides which involves inhibition of folic acid synthesis in susceptible organisms. It is also used with pyrimethamine in the treatment of malaria. Antimycobacterial Drugs 50‒75 mg daily
  • Hydroxychloroquine Hydroxychloroquine A chemotherapeutic agent that acts against erythrocytic forms of malarial parasites. Hydroxychloroquine appears to concentrate in food vacuoles of affected protozoa. It inhibits plasmodial heme polymerase. Immunosuppressants 200 mg twice daily
  • Colchicine Colchicine A major alkaloid from colchicum autumnale l. And found also in other colchicum species. Its primary therapeutic use is in the treatment of gout. Gout Drugs 1‒2 mg daily (especially for Behçet disease)
  • Tumor Tumor Inflammation necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage factor ( TNF TNF Tumor necrosis factor (TNF) is a major cytokine, released primarily by macrophages in response to stimuli. The presence of microbial products and dead cells and injury are among the stimulating factors. This protein belongs to the TNF superfamily, a group of ligands and receptors performing functions in inflammatory response, morphogenesis, and cell proliferation. Tumor Necrosis Factor (TNF))-α inhibitors (consider in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with IBD after infection/ TB TB 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 has been ruled out):
    • Etanercept Etanercept A recombinant version of soluble human tnf receptor fused to an IgG Fc fragment that binds specifically to tumor necrosis factor and inhibits its binding with endogenous tnf receptors. It prevents the inflammatory effect of tnf and is used to treat rheumatoid arthritis; psoriatic arthritis and ankylosing spondylitis. Immunosuppressants
    • Adalimumab Adalimumab A humanized monoclonal antibody that binds specifically to tnf-alpha and blocks its interaction with endogenous tnf receptors to modulate inflammation. It is used in the treatment of rheumatoid arthritis; psoriatic arthritis; Crohn’s disease and ulcerative colitis. Disease-Modifying Antirheumatic Drugs (DMARDs)

Identify and manage the underlying cause, such as:^[1‒4,7]

• Appropriate antimicrobials for 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
• Discontinuing potential offending medications (if possible)
• Cancer treatment (e.g., chemotherapy Chemotherapy Osteosarcoma) for malignancies

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 ( erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion induratum of Bazin): a lobular panniculitis Panniculitis General term for inflammation of adipose tissue, usually of the skin, characterized by reddened subcutaneous nodules. Erythema Nodosum 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 Calves Erythema Nodosum 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 Panniculitis General term for inflammation of adipose tissue, usually of the skin, characterized by reddened subcutaneous nodules. Erythema Nodosum: 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, typically affecting the lower trunk and proximal extremities. This condition may be associated with emphysema Emphysema Enlargement of air spaces distal to the terminal bronchioles where gas-exchange normally takes place. This is usually due to destruction of the alveolar wall. Pulmonary emphysema can be classified by the location and distribution of the lesions. Chronic Obstructive Pulmonary Disease (COPD) or hepatic dysfunction.
• Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion nodosum leprosum: a type 2 Type 2 Spinal Muscular Atrophy leprosy Leprosy Leprosy, also known as Hansen’s disease, is a chronic bacterial infection caused by Mycobacterium leprae complex bacteria. Symptoms primarily affect the skin and peripheral nerves, resulting in cutaneous manifestations (e.g., hypopigmented macules) and neurologic manifestations (e.g., loss of sensation). Leprosy reaction (an immune-mediated severe multisystem complication of leprosy Leprosy Leprosy, also known as Hansen’s disease, is a chronic bacterial infection caused by Mycobacterium leprae complex bacteria. Symptoms primarily affect the skin and peripheral nerves, resulting in cutaneous manifestations (e.g., hypopigmented macules) and neurologic manifestations (e.g., loss of sensation). Leprosy) that presents with widespread groups of tender subcutaneous nodules and/or erythematous plaques, primarily located on the face and extensor surfaces of the extremities. Systemic symptoms may also be present

Clinical Relevance

• EN EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum 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 EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum 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 ( Löfgren syndrome LöFGRen syndrome An acute presentation of sarcoidosis lasting weeks to months that usually resolves spontaneously without treatment and is seen typically in younger adults. Sarcoidosis triad of EN EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum, 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 EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum may precede or be coincident with an acute flare of inflammatory bowel disease