Materiały źródłowe

• #1 Erythema Nodosum – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK470369/

  Erythema nodosum (EN) is a common acute nodular septal panniculitis, characterized by the sudden onset of erythematous, firm, solid, deep nodules or plaques that are painful on palpation and mainly localized on extensor surfaces of the legs. […] Erythema nodosum is an acute or recurrent hypersensitivity reaction to a variety of antigens with a clear female predominance that may be associated with several different stimuli or pathological conditions. […] EN is the result of a nonspecific cutaneous reaction to various antigens. The mechanism involved would be immunologically mediated. Numerous direct and indirect evidence supports the notion of type IV delayed hypersensitivity response to many antigens. It is postulated that the pathogenesis may be due to the deposition of immune complexes in the venules of subcutaneous fat, the production of oxygen free radicals, TNF-alpha, and granuloma formation. However, this hypothesis is not accepted by all authors.

• #2 Erythema Nodosum: A Practical Approach and Diagnostic Algorithm

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7938036/

  Erythema nodosum is considered a hypersensitivity response to a variety of antigenic stimuli. […] It has been proposed that EN may be the result of the formation of immune complexes and their deposition in the venules of the septae of the subcutaneous fat. […] Evidence of circulating immune complexes in early lesions supports the suggestion that the antigen, antibody, and complement play a significant role in the pathogenesis and circulating immune complexes may contribute to tissue injury. […] However, some authors have reported a lack of circulating immune complexes in uncomplicated EN, and a type IV delayed hypersensitivity reaction has been proposed. […] Several adhesion molecules and inflammatory mediators are involved in the development of the lesions. […] Expression of adhesion molecules, such as E-selectin, P-selectin, platelet endothelial cell adhesion molecule, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1, on endothelial cells in patients with EN has been observed.

• #2 Erythema Nodosum: A Sign of Systemic Disease | AAFP

  https://www.aafp.org/pubs/afp/issues/2007/0301/p695.html

  Erythema nodosum is a nonspecific cutaneous reaction pattern to a variety of antigens, with many immune-mediated mechanisms implicated. […] Most direct and indirect evidence supports the involvement of a type IV delayed hypersensitivity response to numerous antigens. […] Erythema nodosum represents an inflammation of the septa in the subcutaneous fat tissue: a septal panniculitis. […] A neutrophilic infiltrate around proliferating capillaries results in septal thickening in early lesions that may be associated with hemorrhage. […] Actinic (Miescher’s) radial granulomas are a characteristic finding. […] Erythema nodosum is not associated with vasculitis, although small vessel inflammation and hemorrhage can occur.

• #3 Erythema Nodosum – Dermatologic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/dermatologic-disorders/hypersensitivity-and-reactive-skin-disorders/erythema-nodosum

  Erythema nodosum is a specific form of panniculitis characterized by tender, red or violet, palpable, subcutaneous nodules on the shins and occasionally other locations. […] Etiology of erythema nodosum is unknown, but an immunologic reaction is suspected because erythema nodosum is frequently accompanied by other disorders. […] Up to about 50% of cases of erythema nodosum are idiopathic. […] Diagnosis of erythema nodosum is usually by clinical appearance and can be confirmed by incisional wedge biopsy of a nodule when necessary. […] A diagnosis of erythema nodosum should prompt evaluation for causes. […] Erythema nodosum almost always resolves spontaneously (typically over about 3 to 6 weeks). […] If an underlying disorder is identified, it should be treated.

• #3 Erythema Nodosum | Concise Medical Knowledge

  https://www.lecturio.com/concepts/erythema-nodosum/

  An immune-mediated reaction to various antigens results in subcutaneous fat inflammation. […] 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, Meischers radial granulomas, and multinucleated giant cells. Secondary vasculitis may be seen if there are dense neutrophil infiltrates.

• #4 Erythema nodosum – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/dermatology/erythema-nodosum-3/

  Erythema nodosum (EN) is the most common form of panniculitis. EN is generally viewed as a cutaneous reactive process that can be seen as an isolated, idiopathic condition (sometimes referred to as primary EN), or more often as a skin sign of another disease (secondary EN). […] The underlying disease often depends on the regional and seasonal setting in which the patient presents; in areas of endemic tuberculosis, for instance, TB may be a more likely trigger for EN than sarcoidosis; conversely, most cases are seen early in the calendar year, when streptococcal infections are most prevalent. […] Although numbers vary, generally in half of the patients with EN, an underlying etiology can be determined (infections, medications, systemic diseases, as noted elsewhere). The actual cause of the septal inflammation itself, though, remains uncertain. Many feel that the panniculitis is a form of a type IV delayed hypersensitivity reaction in response to a triggering antigen. The wide range of associated diseases and potential antigens suggests EN is a nonspecific inflammatory reaction pattern, potentially in response to multiple stimuli. […] Overall, EN likely represents a cutaneous reaction pattern of septal inflammation and panniculitis due to an array of triggering factors and stimuli that set off an inflammatory cascade leading to early neutrophil activation and progressive fibrosis.

• #5 Erythema Nodosum: A Practical Approach and Diagnostic Algorithm

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7938036/

  Erythema nodosum is considered a hypersensitivity response to a variety of antigenic stimuli. […] It has been proposed that EN may be the result of the formation of immune complexes and their deposition in the venules of the septae of the subcutaneous fat. […] Evidence of circulating immune complexes in early lesions supports the suggestion that the antigen, antibody, and complement play a significant role in the pathogenesis and circulating immune complexes may contribute to tissue injury. […] However, some authors have reported a lack of circulating immune complexes in uncomplicated EN, and a type IV delayed hypersensitivity reaction has been proposed. […] Several adhesion molecules and inflammatory mediators are involved in the development of the lesions. […] Expression of adhesion molecules, such as E-selectin, P-selectin, platelet endothelial cell adhesion molecule, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1, on endothelial cells in patients with EN has been observed.

• #6 Erythema nodosum

  https://escholarship.org/uc/item/4829t6rn

  Erythema nodosum is considered to be a hypersensitivity response to a wide variety of inciting factors. […] The variability of possible antigenic stimuli that can induce erythema nodosum indicates that this disorder is a cutaneous reactive process and that the skin has limited responses to different provoking agents. Erythema nodosum probably results from the formation of immune complexes and their deposition in and around venules of the connective tissue septa of the subcutaneous fat. […] Circulating immunocomplexes and complement activation have been recorded in patients with erythema nodosum. […] Histopathologic features in fully developed lesions also suggest a delayed hypersensitivity mechanism and direct immunofluorescence studies have shown deposits of immunoglobulins in the blood vessel walls of the septa of subcutaneous fat.

• #7 Erythema Nodosum – Rheumatology – Diseases – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.II.16.25.

  Erythema nodosum refers to inflammatory nodular lesions in the subcutaneous tissue characterized histologically by septal inflammation. Immune complexes are thought to play a role in the pathogenesis. […] Diagnosis is based on clinical features. A skin biopsy is performed in exceptional cases, for instance, when the condition needs to be differentiated from idiopathic panniculitis (Weber-Christian disease). […] Differential diagnosis also includes all the conditions that may cause erythema nodosum (see Definition, Etiology, Pathogenesis, above).

• #8 Erythema nodosum – Wikipedia

  https://en.wikipedia.org/wiki/Erythema_nodosum

  Erythema nodosum is probably a delayed hypersensitivity reaction to a variety of antigens. […] Although circulating immune complexes have been demonstrated in patients with inflammatory bowel disease, they have not been found in idiopathic or uncomplicated cases.

• #9 Erythema nodosum

  https://escholarship.org/uc/item/4829t6rn

  However, other authors failed to demonstrate circulating immunocomplexes in patients with erythema nodosum, and a type IV delayed hypersensitivity reaction may also play an important role in the pathogenesis of the disorder. […] Early lesions of erythema nodosum are histopathologically characterized by a neutrophilic inflammatory infiltrate involving the septa of the subcutaneous tissue. […] Recent investigations have demonstrated that patients suffering from erythema nodosum had a fourfold higher percentage of reactive oxygen intermediates (ROI) produced by activated neutrophils in their peripheral blood compared with healthy volunteers. […] Furthermore, the percentage of ROI-producing cells in patients with erythema nodosum correlated with the clinical severity. […] These data support that ROI might play a role in the pathogenesis of erythema nodosum.

• #10 Erythema nodosum – Cancer Therapy Advisor

  https://www.cancertherapyadvisor.com/home/decision-support-in-medicine/hospital-medicine/erythema-nodosum/

  Erythema nodosum has long been considered a hypersensitivity response to a wide variety of inciting factors. […] The large variability of potential antigenic triggers that can induce EN suggests that this disorder is a cutaneous reactive process. […] A delayed type of hypersensitivity reaction is suggested based on histopathologic features and despite the fact that direct immunofluorescence studies have shown the very occasional finding of immunoglobulin/immunoreactant deposits in the blood vessel walls of the septa in the subcutaneous fat, an immune complex-mediated vasculitis is not considered likely. […] It is probable that EN represents a nonspecific hypersensitivity reaction that involves a delayed type of hypersensitivity mechanism in addition to a type 3 component. […] Neutrophils are numerous in early lesions and produce reactive oxygen intermediates; these intermediates are suspected to provoke inflammation and tissue damage.

• #11 Erythema Nodosum: A Practical Approach and Diagnostic Algorithm

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7938036/

  Early lesions are characterized by a neutrophilic inflammatory infiltrate in which activated neutrophils might cause oxidative tissue damage and inflammation owing to the production of reactive oxygen intermediates. […] High levels of cytokines and growth factors, mainly involved in neutrophil recruitment and activation, have been reported both in the skin (mainly interleukin [IL]-6, IL-8, IL-12, interferon-, granulocyte colony-stimulating factor and monocyte chemoattractant protein-1) and serum (mainly IL-6, IL-8, IL-12, tumor necrosis factor-, interferon-, granulocyte colony-stimulating factor, and monocyte chemoattractant protein-1) of patients with EN. […] Increased acute-phase reactants have been detected in patients with EN.

• #12 Erythema nodosum

  https://escholarship.org/uc/item/4829t6rn

  However, other authors failed to demonstrate circulating immunocomplexes in patients with erythema nodosum, and a type IV delayed hypersensitivity reaction may also play an important role in the pathogenesis of the disorder. […] Early lesions of erythema nodosum are histopathologically characterized by a neutrophilic inflammatory infiltrate involving the septa of the subcutaneous tissue. […] Recent investigations have demonstrated that patients suffering from erythema nodosum had a fourfold higher percentage of reactive oxygen intermediates (ROI) produced by activated neutrophils in their peripheral blood compared with healthy volunteers. […] Furthermore, the percentage of ROI-producing cells in patients with erythema nodosum correlated with the clinical severity. […] These data support that ROI might play a role in the pathogenesis of erythema nodosum.

• #13

  https://journals.lww.com/idoj/fulltext/2014/05030/role_of_tetracycline_in_recalcitrant_erythema.16.aspx

  Erythema nodosum is a type of septal panniculitis. The possible mechanism of action of tetracycline is analyzed. Tetracycline should be considered as a logical option in recalcitrant erythema nodosum. […] Authors have postulated that tetracycline prevents lipolysis and fat necrosis. A possible role of reactive oxygen species in the pathogenesis of EN has been suggested. Tetracyclines have the ability to scavenge reactive oxygen species. This might be the one of the possible ways by which our patient showed improvement with tetracycline.

• #14 Erythema nodosum

  https://escholarship.org/uc/item/4829t6rn

  However, other authors failed to demonstrate circulating immunocomplexes in patients with erythema nodosum, and a type IV delayed hypersensitivity reaction may also play an important role in the pathogenesis of the disorder. […] Early lesions of erythema nodosum are histopathologically characterized by a neutrophilic inflammatory infiltrate involving the septa of the subcutaneous tissue. […] Recent investigations have demonstrated that patients suffering from erythema nodosum had a fourfold higher percentage of reactive oxygen intermediates (ROI) produced by activated neutrophils in their peripheral blood compared with healthy volunteers. […] Furthermore, the percentage of ROI-producing cells in patients with erythema nodosum correlated with the clinical severity. […] These data support that ROI might play a role in the pathogenesis of erythema nodosum.

• #15 Erythema nodosum in a quiescent phase of ulcerative colitis | The Foot and Ankle Online Journal

  https://faoj.org/2019/12/31/erythema-nodosum-in-a-quiescent-phase-of-ulcerative-colitis/

  Erythema nodosum is inflammation of subcutaneous fat tissue. It presents secondary to many etiologies such as infection, drugs, malignancy, and inflammatory bowel disease. […] Erythema nodosum (EN) is the most common type of septal panniculitis, which is inflammation of subcutaneous fat tissue. EN can be idiopathic or could be a sign of an underlying systemic disease such as infection, drugs, pregnancy, malignancy, and inflammatory conditions such as sarcoidosis and inflammatory bowel disease. […] Erythema nodosum is a form of panniculitis, inflammation of subcutaneous fat tissue. Most cases occur between the ages of 20 and 45 and are 3 to 6 times more common in women than men. EN is a delayed-hypersensitivity reaction and is thought to result from the formation of immune complexes and their deposition in venules of the subcutaneous fat. Histopathologically, neutrophilic inflammatory infiltrate involving the septa of the subcutaneous tissue has been noted along with a fourfold higher percentage of reactive oxygen intermediates produced by activated neutrophils.

• #16 Erythema Nodosum: A Practical Approach and Diagnostic Algorithm

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7938036/

  Erythema nodosum is considered a hypersensitivity response to a variety of antigenic stimuli. […] It has been proposed that EN may be the result of the formation of immune complexes and their deposition in the venules of the septae of the subcutaneous fat. […] Evidence of circulating immune complexes in early lesions supports the suggestion that the antigen, antibody, and complement play a significant role in the pathogenesis and circulating immune complexes may contribute to tissue injury. […] However, some authors have reported a lack of circulating immune complexes in uncomplicated EN, and a type IV delayed hypersensitivity reaction has been proposed. […] Several adhesion molecules and inflammatory mediators are involved in the development of the lesions. […] Expression of adhesion molecules, such as E-selectin, P-selectin, platelet endothelial cell adhesion molecule, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1, on endothelial cells in patients with EN has been observed.

• #17 Erythema Nodosum: A Practical Approach and Diagnostic Algorithm

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7938036/

  Early lesions are characterized by a neutrophilic inflammatory infiltrate in which activated neutrophils might cause oxidative tissue damage and inflammation owing to the production of reactive oxygen intermediates. […] High levels of cytokines and growth factors, mainly involved in neutrophil recruitment and activation, have been reported both in the skin (mainly interleukin [IL]-6, IL-8, IL-12, interferon-, granulocyte colony-stimulating factor and monocyte chemoattractant protein-1) and serum (mainly IL-6, IL-8, IL-12, tumor necrosis factor-, interferon-, granulocyte colony-stimulating factor, and monocyte chemoattractant protein-1) of patients with EN. […] Increased acute-phase reactants have been detected in patients with EN.

• #18 Erythema Nodosum in Children: A Narrative Review and a Practical Approach

  https://www.mdpi.com/2227-9067/9/4/511

  Erythema nodosum (EN) is the most frequent form of panniculitis in children. […] The pathogenesis of EN is not fully understood, although several authors consider EN a delayed-type hypersensitivity reaction due to exposure to different antigens (both internal and external). The mechanism may involve immune complex deposition in the septal venules of the subcutaneous fat. […] EN is, in fact, the prototype of septal panniculitis without primary vasculitis: septa of subcutaneous adipose tissue appear thickened and infiltrated by inflammatory cells. Early lesions demonstrate predominant septal edema with prevalent neutrophils and eosinophils infiltrate, resulting in the reactive oxygen species formation; this is followed by a mild infiltrate of activated T lymphocytes CD4 with tumor necrosis factor (TNF) α production. Subsequently, a shift to an infiltrate of lymphocytes, macrophages, histiocytes, and multinucleated giant cells occurs; they aggregate themselves surrounding a cleft-like virtual space or small blood vessels, determining the so-called “Miescher radial granuloma” which is the pathognomonic EN feature. […] High levels of interleukins (IL) (IL-6, IL-8, IL-12) and growth factors (TNF-α, interferon-γ, granulocyte colony-stimulating factor and monocyte chemoattractant protein-1) mainly involved in neutrophil recruitment and activation, have been reported in the skin and serum of EN patients.

• #19 Erythema nodosum

  https://escholarship.org/uc/item/4829t6rn

  Patients with erythema nodosum associated with sarcoidosis produce an uncommon tumor necrosis factor, TNF- II. […] These patients showed a nucleotide exchange, (G-A) at position -308 in the human TNF- gene promoter, whereas patients with erythema nodosum without underlying sarcoidosis displayed a similar allele frequency compared with controls. […] These results support the notion that erythema nodosum in association with sarcoidosis might be pathogenetically linked to altered TNF- production due to a genetic promoter polymorphism. […] In contrast, other authors have found that the proinflammatory cytokine pattern showed increased interleukin-6 serum concentrations both in infectious and non infectious disease-related erythema nodosum, whereas a minor involvement of TNF was found in these patients.

• #20 Erythema Nodosum in Children: A Narrative Review and a Practical Approach

  https://www.mdpi.com/2227-9067/9/4/511

  Erythema nodosum (EN) is the most frequent form of panniculitis in children. […] The pathogenesis of EN is not fully understood, although several authors consider EN a delayed-type hypersensitivity reaction due to exposure to different antigens (both internal and external). The mechanism may involve immune complex deposition in the septal venules of the subcutaneous fat. […] EN is, in fact, the prototype of septal panniculitis without primary vasculitis: septa of subcutaneous adipose tissue appear thickened and infiltrated by inflammatory cells. Early lesions demonstrate predominant septal edema with prevalent neutrophils and eosinophils infiltrate, resulting in the reactive oxygen species formation; this is followed by a mild infiltrate of activated T lymphocytes CD4 with tumor necrosis factor (TNF) α production. Subsequently, a shift to an infiltrate of lymphocytes, macrophages, histiocytes, and multinucleated giant cells occurs; they aggregate themselves surrounding a cleft-like virtual space or small blood vessels, determining the so-called “Miescher radial granuloma” which is the pathognomonic EN feature. […] High levels of interleukins (IL) (IL-6, IL-8, IL-12) and growth factors (TNF-α, interferon-γ, granulocyte colony-stimulating factor and monocyte chemoattractant protein-1) mainly involved in neutrophil recruitment and activation, have been reported in the skin and serum of EN patients.

• #21 Erythema nodosum pathology

  https://dermnetnz.org/topics/erythema-nodosum-pathology

  Erythema nodosum is the most common form of panniculitis. […] Erythema nodosum histologically represents the prototype of a septal panniculitis. The classic histopathologic presentation of erythema nodosum is that of a septal panniculitis with a mixed cellular infiltrate of lymphocytes, histiocytes, giant cells, and occasional eosinophils and a characteristic absence of vasculitis. […] Early lesions may be difficult to diagnose on histopathologic features alone. Sections may show oedematous septa containing a prominent mixed inflammatory infiltrate, and minimal fibrosis. As the lesions evolve, there is neutrophilic infiltration followed by chronic infiltrates, granulomas and septal fibrosis. […] Small vessel vasculitis (or venulitis) may be seen in early lesions.

• #22 Erythema Nodosum: A Sign of Systemic Disease | AAFP

  https://www.aafp.org/pubs/afp/issues/2007/0301/p695.html

  Erythema nodosum is a nonspecific cutaneous reaction pattern to a variety of antigens, with many immune-mediated mechanisms implicated. […] Most direct and indirect evidence supports the involvement of a type IV delayed hypersensitivity response to numerous antigens. […] Erythema nodosum represents an inflammation of the septa in the subcutaneous fat tissue: a septal panniculitis. […] A neutrophilic infiltrate around proliferating capillaries results in septal thickening in early lesions that may be associated with hemorrhage. […] Actinic (Miescher’s) radial granulomas are a characteristic finding. […] Erythema nodosum is not associated with vasculitis, although small vessel inflammation and hemorrhage can occur.

• #23 Erythema Nodosum in Children: A Narrative Review and a Practical Approach

  https://www.mdpi.com/2227-9067/9/4/511

  Erythema nodosum (EN) is the most frequent form of panniculitis in children. […] The pathogenesis of EN is not fully understood, although several authors consider EN a delayed-type hypersensitivity reaction due to exposure to different antigens (both internal and external). The mechanism may involve immune complex deposition in the septal venules of the subcutaneous fat. […] EN is, in fact, the prototype of septal panniculitis without primary vasculitis: septa of subcutaneous adipose tissue appear thickened and infiltrated by inflammatory cells. Early lesions demonstrate predominant septal edema with prevalent neutrophils and eosinophils infiltrate, resulting in the reactive oxygen species formation; this is followed by a mild infiltrate of activated T lymphocytes CD4 with tumor necrosis factor (TNF) α production. Subsequently, a shift to an infiltrate of lymphocytes, macrophages, histiocytes, and multinucleated giant cells occurs; they aggregate themselves surrounding a cleft-like virtual space or small blood vessels, determining the so-called “Miescher radial granuloma” which is the pathognomonic EN feature. […] High levels of interleukins (IL) (IL-6, IL-8, IL-12) and growth factors (TNF-α, interferon-γ, granulocyte colony-stimulating factor and monocyte chemoattractant protein-1) mainly involved in neutrophil recruitment and activation, have been reported in the skin and serum of EN patients.

• #24 Erythema Nodosum pathogenesis and clinical findings | Calgary Guide

  https://calgaryguide.ucalgary.ca/erythema-nodosum-pathogenesis-and-clinical-findings/erythema-nodosum/

  Erythema Nodosum pathogenesis and clinical findings […] Septal Fibrosis made of inflammatory cells, such as T lymphocytes, histocytes and eosinophils […] Antigenic Stimuli / Bacteria / Viruses / Chemical Agents all could trigger the following process: Phase 1. Neutrophils Infiltrate the fibrous septa between fat lobules in the subcutaneous fat Phase 2. Neutrophils release reactive oxygen species, leading to oxidative tissue damage and inflammation Phase 3. Opening of inter-endothelial junction and the migration of more inflammatory cells into the septal venules, including macrophages, histocytes, and eosinophils Phase 4. Macrophages secrete inflammatory cytokines, which stimulates the proliferation of more helper T cells (Th1) Phase 5. Th1 cells secrete more cytokines, leading to the further release of Th1 cytokines and mediating the immune complexes deposition in the septal venules of the subcutaneous fat (panniculitis). The Th1 immune reaction is called Type IV Delayed Hypersensitivity Reaction Phase 6. Activated macrophages produce hydrolytic enzymes and transform into multi-nucleated giant cells, called Mieschers Radial Granulomas. These consist of small, well defined aggregations of small histocytes arranged radially around a small cleft of variable shapes in the septal venules of the subcutaneous fat

• #25 Erythema nodosum pathology

  https://dermnetnz.org/topics/erythema-nodosum-pathology

  Erythema nodosum is the most common form of panniculitis. […] Erythema nodosum histologically represents the prototype of a septal panniculitis. The classic histopathologic presentation of erythema nodosum is that of a septal panniculitis with a mixed cellular infiltrate of lymphocytes, histiocytes, giant cells, and occasional eosinophils and a characteristic absence of vasculitis. […] Early lesions may be difficult to diagnose on histopathologic features alone. Sections may show oedematous septa containing a prominent mixed inflammatory infiltrate, and minimal fibrosis. As the lesions evolve, there is neutrophilic infiltration followed by chronic infiltrates, granulomas and septal fibrosis. […] Small vessel vasculitis (or venulitis) may be seen in early lesions.

• #26 77 Erythema Nodosum and Other Forms of Panniculitis | Plastic Surgery Key

  https://plasticsurgerykey.com/77-erythema-nodosum-and-other-forms-of-panniculitis/

  Septal panniculitis without vasculitis is the hallmark histopathological feature of erythema nodosum. There is inflammation and thickening of the fibrous septa of the subcutaneous fat. The inflammatory infiltrate varies with the stage of the lesion, ranging from neutrophils in early lesions to lymphocytes, giant cells and granulation tissue in late-stage lesions.

• #27 Erythema Nodosum pathogenesis and clinical findings | Calgary Guide

  https://calgaryguide.ucalgary.ca/erythema-nodosum-pathogenesis-and-clinical-findings/erythema-nodosum/

  Erythema Nodosum pathogenesis and clinical findings […] Septal Fibrosis made of inflammatory cells, such as T lymphocytes, histocytes and eosinophils […] Antigenic Stimuli / Bacteria / Viruses / Chemical Agents all could trigger the following process: Phase 1. Neutrophils Infiltrate the fibrous septa between fat lobules in the subcutaneous fat Phase 2. Neutrophils release reactive oxygen species, leading to oxidative tissue damage and inflammation Phase 3. Opening of inter-endothelial junction and the migration of more inflammatory cells into the septal venules, including macrophages, histocytes, and eosinophils Phase 4. Macrophages secrete inflammatory cytokines, which stimulates the proliferation of more helper T cells (Th1) Phase 5. Th1 cells secrete more cytokines, leading to the further release of Th1 cytokines and mediating the immune complexes deposition in the septal venules of the subcutaneous fat (panniculitis). The Th1 immune reaction is called Type IV Delayed Hypersensitivity Reaction Phase 6. Activated macrophages produce hydrolytic enzymes and transform into multi-nucleated giant cells, called Mieschers Radial Granulomas. These consist of small, well defined aggregations of small histocytes arranged radially around a small cleft of variable shapes in the septal venules of the subcutaneous fat

• #28 Erythema nodosum

  https://escholarship.org/uc/item/4829t6rn

  The reason the anterior aspects of the legs are so susceptible for the development of lesions of erythema nodosum is unknown. […] Some authors have proposed that there is no other site on the skin surface where the combination of a relatively sparse arterial supply is associated with a venous system subject to gravitational effects and cooling and a lymphatic system which is hardly rich enough to meet the requirements of any increase in fluid load and which has no mechanical stimulus. […] The skin of the shins has no underlying muscle pump and receives little in the way of massage. […] All these local anatomic factors would favor the location of the lesions of erythema nodosum on the shins.

• #29 Erythema nodosum – Cancer Therapy Advisor

  https://www.cancertherapyadvisor.com/home/decision-support-in-medicine/hospital-medicine/erythema-nodosum/

  Regardless of the exact mechanism, a wide variety of triggering factors has been linked to erythema nodosum. […] The reason that the anterior aspects of the legs are so susceptible for lesions is unknown. […] Some authors have proposed that there is no other site on the skin surface that has a combination of a relatively sparse arterial supply associated with a venous system subject to gravitational effects and cooling as well as a lymphatic system that is hardly efficient enough to meet the requirements of any increase in fluid load.

• #30 Erythema nodosum

  https://escholarship.org/uc/item/4829t6rn

  The reason the anterior aspects of the legs are so susceptible for the development of lesions of erythema nodosum is unknown. […] Some authors have proposed that there is no other site on the skin surface where the combination of a relatively sparse arterial supply is associated with a venous system subject to gravitational effects and cooling and a lymphatic system which is hardly rich enough to meet the requirements of any increase in fluid load and which has no mechanical stimulus. […] The skin of the shins has no underlying muscle pump and receives little in the way of massage. […] All these local anatomic factors would favor the location of the lesions of erythema nodosum on the shins.

• #31 Erythema nodosum – Cancer Therapy Advisor

  https://www.cancertherapyadvisor.com/home/decision-support-in-medicine/hospital-medicine/erythema-nodosum/

  Erythema nodosum has long been considered a hypersensitivity response to a wide variety of inciting factors. […] The large variability of potential antigenic triggers that can induce EN suggests that this disorder is a cutaneous reactive process. […] A delayed type of hypersensitivity reaction is suggested based on histopathologic features and despite the fact that direct immunofluorescence studies have shown the very occasional finding of immunoglobulin/immunoreactant deposits in the blood vessel walls of the septa in the subcutaneous fat, an immune complex-mediated vasculitis is not considered likely. […] It is probable that EN represents a nonspecific hypersensitivity reaction that involves a delayed type of hypersensitivity mechanism in addition to a type 3 component. […] Neutrophils are numerous in early lesions and produce reactive oxygen intermediates; these intermediates are suspected to provoke inflammation and tissue damage.

• #32

  https://link.springer.com/article/10.1007/s40257-021-00592-w

  Erythema nodosum is the most common form of panniculitis and is characterized by tender erythematous nodules mainly in the lower limbs on the pretibial area. The exact cause of erythema nodosum is unknown, although it appears to be a hypersensitivity response to a variety of antigenic stimuli. […] Although the etiology is mostly idiopathic, ruling out an underlying disease is imperative before diagnosing primary erythema nodosum. Erythema nodosum can be the first sign of a systemic disease that is triggered by a large group of processes, such as infections, inflammatory diseases, neoplasia, and/or drugs. […] Making an accurate diagnosis will allow the physician to treat the underlying cause and determine an optimal therapeutic strategy.

• #33 Erythema Nodosum | SpringerLink

  https://link.springer.com/10.1007%2F978-3-540-29676-8_583

  The exact pathophysiology of EN is unknown. Currently, it is recognized as a delayed hypersensitivity reaction that can be triggered by a wide variety of antigenic stimuli including bacterial, viral, fungal and protozoal infections; drugs; benign and malignant systemic diseases. […] Streptococcal infection and sarcoidosis are the most commonly…

• #34

  https://link.springer.com/article/10.1007/s40257-021-00592-w

  Erythema nodosum is the most common form of panniculitis and is characterized by tender erythematous nodules mainly in the lower limbs on the pretibial area. The exact cause of erythema nodosum is unknown, although it appears to be a hypersensitivity response to a variety of antigenic stimuli. […] Although the etiology is mostly idiopathic, ruling out an underlying disease is imperative before diagnosing primary erythema nodosum. Erythema nodosum can be the first sign of a systemic disease that is triggered by a large group of processes, such as infections, inflammatory diseases, neoplasia, and/or drugs. […] Making an accurate diagnosis will allow the physician to treat the underlying cause and determine an optimal therapeutic strategy.

• #35 Multiple tender, deep nodules on the legs of a seven-year-old boy

  https://www1.racgp.org.au/ajgp/2018/march/multiple-tender-deep-nodules

  Erythema nodosum is generally considered to be a type IV delayed hypersensitivity reaction, resulting from the deposition of immune complexes in the subcutaneous fat. However, the exact mechanism is not fully understood. […] There is a range of potential triggers, with post-streptococcal infection the common identifiable cause. […] Other aetiologies include a range of bacterial, viral and fungal infections, medications (notably including the oral contraceptive), chronic inflammatory conditions such as sarcoidosis and inflammatory bowel disease, pregnancy and, rarely, malignancy. […] However, half of all cases of erythema nodosum have no identifiable cause found.

• #36 Erythema Nodosum – Dermatologic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/dermatologic-disorders/hypersensitivity-and-reactive-skin-disorders/erythema-nodosum

  Erythema nodosum is a specific form of panniculitis characterized by tender, red or violet, palpable, subcutaneous nodules on the shins and occasionally other locations. […] Etiology of erythema nodosum is unknown, but an immunologic reaction is suspected because erythema nodosum is frequently accompanied by other disorders. […] Up to about 50% of cases of erythema nodosum are idiopathic. […] Diagnosis of erythema nodosum is usually by clinical appearance and can be confirmed by incisional wedge biopsy of a nodule when necessary. […] A diagnosis of erythema nodosum should prompt evaluation for causes. […] Erythema nodosum almost always resolves spontaneously (typically over about 3 to 6 weeks). […] If an underlying disorder is identified, it should be treated.

• #37 Panniculitis and erythema nodosum. A clinical and biological correlation

  http://www.scielo.org.co/scielo.php?script=sci_abstract&pid=S0121-81232006000400002&lng=e&nrm=iso&tlng=en

  Objective: to assess the frequency, etiologic factors, clinical patterns, histological types of panniculitis, and to correlate the different histologic patterns with stages of the disease. […] A correlation between the clinical, histological and immunohistochemical findings, according to the stage of the lesions were established. […] Of the 26 studies realized, histologically vasculitis was found in 2 cases, 6 cases were deemed to be in early stages of EN (23%), 12 (46%) were well developed active EN, and 6 (23%) exhibited late stage and in regression. […] In early stages APC (DR, DP, DQ, CD35) and CD45Ro were the dominant types; in active lesions CD45Ro and to a lesser degree APC and macrophages (CD68) were the predominant cell types. […] In late stages CD45Ro lymphocytes were the dominant cell types.

• #38 Erythema Nodosum – Dermatologic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/dermatologic-disorders/hypersensitivity-and-reactive-skin-disorders/erythema-nodosum

  Erythema nodosum is a specific form of panniculitis characterized by tender, red or violet, palpable, subcutaneous nodules on the shins and occasionally other locations. […] Etiology of erythema nodosum is unknown, but an immunologic reaction is suspected because erythema nodosum is frequently accompanied by other disorders. […] Up to about 50% of cases of erythema nodosum are idiopathic. […] Diagnosis of erythema nodosum is usually by clinical appearance and can be confirmed by incisional wedge biopsy of a nodule when necessary. […] A diagnosis of erythema nodosum should prompt evaluation for causes. […] Erythema nodosum almost always resolves spontaneously (typically over about 3 to 6 weeks). […] If an underlying disorder is identified, it should be treated.

• #39

  https://journals.lww.com/jdpa/fulltext/2018/12030/erythema_nodosum__a_review_and_approach_to.4.aspx

  Erythema nodosum is a variant of panniculitis most commonly characterized by tender subcutaneous nodules and plaques on the pretibial surface of the bilateral lower extremities. […] Numerous etiologies have been linked to trigger erythema nodosum, though the pathogenesis of development is poorly understood. […] If identified, treatment should be directed to management of the underlying etiology of erythema nodosum, but supportive measures may be used to improve patient discomfort associated with the classic skin findings.

• #40 Erythema Nodosum – Dermatologic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/dermatologic-disorders/hypersensitivity-and-reactive-skin-disorders/erythema-nodosum

  Erythema nodosum is a specific form of panniculitis characterized by tender, red or violet, palpable, subcutaneous nodules on the shins and occasionally other locations. […] Etiology of erythema nodosum is unknown, but an immunologic reaction is suspected because erythema nodosum is frequently accompanied by other disorders. […] Up to about 50% of cases of erythema nodosum are idiopathic. […] Diagnosis of erythema nodosum is usually by clinical appearance and can be confirmed by incisional wedge biopsy of a nodule when necessary. […] A diagnosis of erythema nodosum should prompt evaluation for causes. […] Erythema nodosum almost always resolves spontaneously (typically over about 3 to 6 weeks). […] If an underlying disorder is identified, it should be treated.

• #41 Erythema nodosum – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/dermatology/erythema-nodosum-3/

  Erythema nodosum (EN) is the most common form of panniculitis. EN is generally viewed as a cutaneous reactive process that can be seen as an isolated, idiopathic condition (sometimes referred to as primary EN), or more often as a skin sign of another disease (secondary EN). […] The underlying disease often depends on the regional and seasonal setting in which the patient presents; in areas of endemic tuberculosis, for instance, TB may be a more likely trigger for EN than sarcoidosis; conversely, most cases are seen early in the calendar year, when streptococcal infections are most prevalent. […] Although numbers vary, generally in half of the patients with EN, an underlying etiology can be determined (infections, medications, systemic diseases, as noted elsewhere). The actual cause of the septal inflammation itself, though, remains uncertain. Many feel that the panniculitis is a form of a type IV delayed hypersensitivity reaction in response to a triggering antigen. The wide range of associated diseases and potential antigens suggests EN is a nonspecific inflammatory reaction pattern, potentially in response to multiple stimuli. […] Overall, EN likely represents a cutaneous reaction pattern of septal inflammation and panniculitis due to an array of triggering factors and stimuli that set off an inflammatory cascade leading to early neutrophil activation and progressive fibrosis.

• #42 Erythema nodosum as a cutaneous manifestation of COVID-19 infection | BMJ Case Reports

  https://casereports.bmj.com/content/13/7/e236613

  Erythema nodosum (EN) is a common dermatological manifestation with many different aetiologies. […] Exact pathogenesis remains unclear, but most evidence supports the involvement of a type IV delayed hypersensitivity response to various antigens. […] EN remains a self-limiting condition and usually resolves within a few weeks, although the exact aetiology frequently remains unidentified and untreated. […] The distinctive feature of our case was this young patient without medical history presenting a cutaneous inflammatory manifestation associated with fever, cough and shortness of breath in the context of a COVID-19 infection. […] Erythema nodosum (EN) is a common cutaneous manifestation with until now no known pathogenesis.

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