Erythema nodosum leprosum: nature and extent of the cutaneous microvascular alterations

Skin biopsy specimens from four patients with erythema nodosum leprosum, when examined as Epon-embedded, 1-micron sections, exhibited a necrotizing vasculitis involving capillaries, venules, and small-to-medium arteries and veins. In the superficial dermis, affected venules and capillaries showed endothelial cell enlargement and focal necrosis associated with perivascular infiltrates of lymphocytes. In the deep dermis and subcutaneous tissue, affected venules, arterioles, and arteries exhibited endothelial cell necrosis and matted fibrin in the vessel walls associated with perivascular infiltrates of neutrophils. Throughout the dermis, mononuclear phagocytes with vacuoles containing numerous fragmented organisms were observed. By electron microscopy, electron-dense material resembling immune complexes was observed in the walls of these vessels. These observations support the concept that erythema nodosum leprosum is an immune complex-mediated necrotizing vasculitis involving capillaries, arterioles, arteries, venules, and veins.     

Erythema nodosum-like lesions in Behçet''s syndrome: a histopathologic study of 30 cases

Thirty patients who fulfilled the criteria for complete and incomplete types of Behçet's syndrome were studied to determine the histopathologic changes of erythema nodosum-like lesions. Lymphocytic vasculitis was observed in 12 (40%) of the cases, but it was only focal in areas of severe lymphocytic inflammation and only mild in degree. No diffuse vasculitis was seen. It is our opinion that the observed lymphocytic vasculitis is only secondary to moderate or severe lymphocytic inflammation. Twelve cases (40%) revealed septal panniculitis, 10 cases (33%) demonstrated lobular panniculitis with moderate to marked inflammation and fat cell necrosis, and 8 cases (27%) showed mild and nonspecific inflammation in the panniculus. Therefore, there is a spectrum of histopathologic changes of erythema nodosum-like lesions in Behçet's syndrome, similar to that of erythema nodosum secondary to other systemic disorders.     

Fluctuating facial edema as a rare manifestation of cutaneous polyarteritis nodosa: Case report and review of the literature

Polyarteritis nodosa (PAN) is a necrotizing vasculitis. The clinical manifestations are determined by the location of the compromised arteries. Cutaneous PAN can present as nodular lesions similar to erythema nodosum, palpable purpura, livedo reticularis, and ulceration. It often affects the lower limbs but other anatomical sites can also be involved. However, concomitant facial edema is an extremely rare manifestation. It has been more than 20 years since the last case report describing this unusual presentation of PAN. Furthermore, our patient is the first case presenting with hemifacial edema fluctuating every second or third day due to PAN confirmed by skin biopsy.     

Yersiniosis

A survey was undertaken about bacteriologic, epidemiologic and clinical features of infections caused by Yersinia. Yersinia enterocolitica and Yersinia pseudotuberculosis are gram negative rods of the enterobacteriaceae family. The number of cases of these infections has increased considerably in the past few years. Erythema nodosum often occurs after an enteritic infection by Yersinia. Other skin manifestations are erythema exsudativum multiforme, erythema figuratum and "drug-eruption-like exanthema". Moreover, Yersinia-arthritis may occur. In one particular case a Reiter-syndrome was described. The mechanism whereby Yersinia induce skin lesions is unknown. Prognosis is good. Therapy of choice for infections caused by Yersinia are tetracyclines.     

Immunological evaluation of erythema nodosum in tularaemia

During two tularaemia outbreaks in the Bursa region of Turkey in 1991, a total of 98 patients were diagnosed and evaluated. Thirteen of these patients had erythema nodosum, which is accepted as a secondary skin manifestation. The patients with erythema nodosum, 21 patients without any skin lesions, and 20 healthy controls were studied. Comparable elevations of levels of IgG, IgA, and IgM were detected in the two tularaemia groups. There was no difference in complement C3c and C4 levels between the groups. All of the patients with erythema nodosum had elevated circulating immune complex (CIC) levels, when compared with the patients without skin lesions and the control group. The acute phase response (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) of the erythema nodosum group was significantly higher than the patients with normal skin, and healthy controls (P> 0.001). Serum transferrin levels were significantly decreased in both of the tularaemia groups (P>0.001). Serum soluble interleukin-2 receptor levels (SIL-2R) were significantly elevated in both tularaemia groups (P>0.001), and the elevation was more marked in the erythema nodosum group (P> 0.05). Histopathologicai evaluation of biopsies from two patients with erythema nodosum showed dermal oedema, a perivascular lymphocytic infiltrate, and panniculitis. No immunoglobulin or complement deposits were detected on immunofluorescence. Erythema nodosum in the course of tularaemia is associated with many immunological changes, although it is not clear whether these findings are related to the increased tissue response, or whether they play a role in the pathogenesis of the erythema nodosum.     

Acute infectious id panniculitis/panniculitic bacterid: a distinctive form of neutrophilic lobular panniculitis

Background: Lobular panniculitis encompasses lupus profundus, atypical lymphocytic lobular panniculitis, erythema induratum and subcutaneous Sweet’s syndrome, while septal panniculitis includes erythema nodosum and fibrosing dermal processes of burn out necrobiosis lipoidica and morphea profundus. Panniculitis may represent a sign of systemic disease and/or a modified immune response to hematogenously disseminated antigen. Methods: We describe 10 cases of sterile neutrophilic dominant lobular panniculitis that represented an id reaction to non‐tuberculous stimuli. Results: Four males and six females had sudden tender non‐ulcerated lower extremity nodules with preceding non‐tuberculous infectious triggers. Three also had upper extremity lesions. Biopsies showed dominant neutrophilic infiltrate with subcutaneous microabscesses (7), extravascular granulomatous infiltrates (5), thrombotic microangiopathy (5) and necrotizing vasculitis (5). Stains evaluating microbial pathogens were negative. Lesions resolved with antibiotic treatment and/or abscess drainage; no case recurred. Medical histories included atopic diathesis (4), primary antiphospholipid antibody syndrome (1), ulcerative colitis (1) and acute lymphocytic leukemia (1). Serologies showed polyclonal hypergammaglobulinemia, cold agglutinins and cryofibrinogens. Conclusions: We propose the term acute infectious id panniculitis for cases of neutrophilic lobular panniculitis triggered by non‐tuberculous infectious stimuli. This course may be self‐limited. Microvascular cofactors and/or procoagulant states may be pathogenetically important. Recognizing this entity may circumvent the need for an exhaustive evaluation for other causes of neutrophilic lobular panniculitis.     

结节性红斑与硬结性红斑皮损原位抗原研究

采用ＰＡＰ法对结节性红斑、慢性游走性结节性红斑、硬红斑及结节性血管炎４种疾病共３５例的原位抗原进行检测。结果在血管的检出例数分别为１１／１２，８／８，８／８，６／７；在胶原纤维表面的检出例数分别为１１／１２，７／８，８／８，６／７；所有病例表皮角朊细胞内均能检出；在血管腔内与血管腔外的红细胞表面的检出例数除慢性游走性结节性红斑为５／８外，其余病种均能检出。提示结节性红斑等４种疾病均为存在免疫复合物     

HLA-DR expression on keratinocytes is a common feature of diseased skin

Biopsy specimens from 185 patients with 52 different skin disorders were investigated by indirect immunofluorescence staining for the presence of HLA-DR bearing keratinocytes and their association with an underlying inflammatory infiltrate and in particular with activated (HLA-DR-positive, Leu-4-positive) T lymphocytes. HLA-DR expression on keratinocytes was demonstrated in 38 dermatoses, including lymphocytic vasculitis, lupus erythematosus, morphea, vitiligo, lichen planus, cutaneous T-cell lymphoma, various infectious dermatoses, allergic contact dermatitis, granulomatous dermatoses, Sweet's syndrome, lichen sclerosus and erythema nodosum. In 27 of these this had not previously been reported. Occurrence of HLA-DR on keratinocytes was invariably linked to the presence of a lymphocytic infiltrate containing numerous activated T-cells (Leu-4 +, HLA-DR +) whereas such infiltrates were not accompanied by HLA-DR expression on keratinocytes in all the dermatoses investigated, as in pseudolymphoma and erythema anulare centrifugum. However, HLA-DR positive keratinocytes were consistently absent in skin disorders lacking any significant lymphocytic infiltration (e.g. leukocytoclastic vasculitis, bullous autoimmune dermatoses, genodermatoses and mastocytosis). Although it has been suggested that HLA-DR-positive keratinocytes are involved in various immune responses of the skin, their exact functional significance is, as yet, unknown.     

Takayasu's disease with cutaneous involvement

Takayasu's arteritis (TA) is a chronic inflammatory and fibrosing arteriopathy that can also involve cutaneous vessels. The disease typically presents with a prepulseless phase that overlaps or is followed by the characteristic pulseless stage. In both phases of TA, cutaneous manifestations may be present. Lesions considered to be 'specifically' associated with TA have been described most frequently simulating erythema nodosum, erythema induratum and pyoderma gangrenosum. We report 2 Caucasian patients with TA and nodular cutaneous lesions. Nine skin biopsies from these patients were studied. A necrotizing vasculitis was present in 5 biopsies. We review those patients with TA and well-documented cutaneous manifestations in the English literature, with special interest in nodular lesions, the most frequent cutaneous manifestation of TA in Caucasian patients. Biopsies from lesions with similar morphology frequently show different histological findings.     

Kutane Vaskulitiden

Vasculitis is characterized by an inflammatory reaction of vessel walls with damage to the dependent tissues. Forms of vasculitis which frequently have skin changes include leukocytoclastic angiitis (LcV), Henoch-Schönlein purpura (HSP), cutaneous polyarteriitis nodosum (cPAN), erythema elevatum et diutinum (EED) and urticarial vasculitis (UV). In other forms of vasculitis, systemic manifestations predominate but there are a variety of skin changes. Kawasaki disease (MK), cryoglobulinemic vasculitis (kV), Wegener granulomatosis (WG), Churg-Strauss syndrome (CSS) and microscopic polyangitis (MPA) belong to this group. The causes of vasculitis are heterogeneous. Triggers include infections, drugs, collagen vascular diseases, autoimmune diseases and lymphoproliferative disorders. Idiopathic vasculitis, particularly LcV and EED, occur only once and have a self-limited course. The diagnostic work up depends on the clinical picture and includes inflammatory markers, circulating immune complexes, different types of cryoglobulins and anti-neutrophilic cytoplasmic antibodies, collagen vascular disease specific autoantibodies and additional hematological studies. Vasculitis can manifest in many organs and requires a thorough work up specifically in cases where WG, MPA, CSS and PAN are under consideration.     

Lymphocytic vasculitis: is it a specific clinicopathologic entity?

Seventy-one biopsy specimens taken at the Mayo Clinic from June 1977 through May 1981 demonstrated lymphocytic vasculitis. All specimens met the criteria for lymphocytic vasculitis, defined as (1) a predominantly lymphocytic infiltrate that involves and surrounds blood vessel walls, (2) fibrinoid necrosis of blood vessel walls, and (3) endothelial cell hyperplasia. Other histologic findings such as thrombosis, extravasation of erythrocytes, ulceration, epidermal infarction, and evidence of nuclear dust were seen only occasionally. Hypocomplementemia and other serologic abnormalities were very rare, even when lymphocytic vasculitis was extensive. The clinical diagnoses varied, with drug reaction (12 patients) and chronic urticaria (10 patients) being most frequent. In 32 cases, no specific diagnosis could be made at the time of dermatologic dismissal. In the remaining 39 cases, the diagnoses were varied and no definite clinical categories can be applied to them. We also observed typical lymphocytic vasculitis in some cases of other clinical entities, such as nodular scabies, erythema multiforme, and urticarial vasculitis, and so forth. We conclude that lymphocytic vasculitis is probably not a specific clinicopathologic entity but is more likely a reactive process, secondary to severe lymphocytic inflammation in the skin.     

Propylthiouracil-induced ANCA-positive erythema nodosum treated with thalidomide

Background Propylthiouracil (PTU), one of the mainstays of antithyroid therapy drugs, can lead to antineutrophil cytoplasmic antibody (ANCA) positivity and skin lesions. PTU‐induced ANCA‐positive vasculitis is rare and even more rare is erythema nodosum. Objective To report a case of a 57‐year‐old woman with hyperthyroidism who developed myeloperoxidase (MPO)‐ANCA erythema nodosum after PTU treatment for 11 months. Methods Skin biopsy demonstrated septal panniculitis without vasculitis. PTU‐induced ANCA‐positive erythema nodosum was made. Results With discontinuation of PTU and initiation of thalidomide, skin lesions resolved completely in three weeks, and after three months, the titers of MPO‐ANCA and perinuclear‐ANCA (p‐ANCA) had decreased remarkably. At 14‐month follow‐up, the patient was asymptomatic, but low levels of ANCA titers persisted. Conclusions This report indicated that ANCA positive erythema nodosum could develop following PTU treatment. Thalidomide has been proven to be helpful and averted the adverse effects from systemic corticosteroids and other immunosuppressive drugs in this patient.     

Circulating immune complexes and necrotizing vasculitis]

55 patients with necrotizing and with various forms of lymphocytic vasculitis were investigated for the presence of vascular deposits of immunoglobulins (Ig) and C3 by immunofluorescence testing of skin biopsies and with a 125I-Clq-binding assay for the presence of circulating immune complexes. Vascular deposits of Ig and C3 were found frequently both in patients with necrotizing and with lymphocytic vasculitis. In contrast, C1q binding activity was found almost exclusively in sera of patients with systemic necrotizing vasculitis. With one exception, all sera with C1q binding activity were from patients with vascular deposits of Ig and C3. The implications of these findings for our understanding of the development of system involvement in necrotizing vasculitis are discussed.     

Erythema nodosum and erythema induratum (nodular vasculitis): diagnosis and management

Erythema nodosum is the most common type of panniculitis; it may be due to a variety of underlying infectious or otherwise antigenic stimuli. The pathogenesis remains to be elucidated, but both neutrophilic inflammation and granulomatous inflammation are implicated. Beyond treating underlying triggers, therapeutic options consist mainly of nonsteroidal anti‐inflammatory drugs, symptomatic care, potassium iodide, and colchicine. Erythema induratum (nodular vasculitis) is a related but distinctly different clinicopathologic reaction pattern of the subcutaneous fat. It is classically caused by an antigenic stimulus from Mycobacterium tuberculosis but may be associated with several other underlying disorders. After appropriate antimicrobial treatment in tuberculous cases, therapy for erythema induratum is similar to options for erythema nodosum.     

Eosinophilic panniculitis: a clinicopathologic study

Study of 18 patients with biopsy diagnoses of eosinophilic panniculitis revealed diverse patterns of systemic disease, including Wells' syndrome, vasculitis, atopy, and erythema nodosum as well as localized panniculitis. Significant associated diseases included psychiatric illness, 6 (drug dependency, 4); atopy, 5 (asthma, 3); malignancies, 5; immune complex vasculitis, 4; thyroid disease, 2; Wells' eosinophilic cellulitis, 2; glomerulonephritis and sarcoidosis, 1 each. The skin lesions varied from urticarial papules and plaques to purpura, pustules, and ulcerative lesions but always included a nodular subcutaneous component, frequently as a presenting complaint. Eosinophilic panniculitis is a non-specific finding that can signify localized disease, such as an insect bite or injection lipophagic granuloma in a drug-dependent patient, or systemic lymphoma or immune reactive disease. Eosinophilic panniculitis in erythema nodosum is perhaps its most confusing presentation.     

Erythema nodosum

Erythema nodosum is the most frequent clinicopathologic variant of panniculitis. The process is a cutaneous reaction that may be associated with a wide variety of disorders, including infections, sarcoidosis, rheumatologic diseases, inflammatory bowel diseases, medications, autoimmune disorders, pregnancy, and malignancies. Histopathologically, erythema nodosum is the stereotypical example of a mostly septal panniculitis with no vasculitis. The composition of the inflammatory infiltrate in the septa varies with age of the lesion. Treatment of erythema nodosum should be directed to the underlying associated condition, if identified.     

Erythema nodosum in association with newly diagnosed hairy cell leukemia and group C streptococcus infection

Erythema nodosum is an inflammatory reaction of the skin characterized by tender erythematous patches or nodules, usually located on the lower extremities. This report illustrates an association of erythema nodosum with a rare malignancy and an uncommon infectious agent in humans. There are many diseases associated with erythema nodosum; we propose that hairy cell leukemia and group C streptococcus be considered among this list.     

TREATMENT OF ERYTHEMATOUS DERMATOSES WITH POTASSIUM IODIDE

Forty-seven patients with various erythematous dermatoses were treated with systemic administration of potassium iodide. There were fifteen patients with erythema nodosum, ten with nodular vasculitis, fourteen with erythema multiforme, and eight with Sweet's syndrome. Potassium iodide was dramatically effective in a substantial number of cases. In responsive patients, improvement of the cutaneous changes was evident within a few days. The effect of the drug was impressive in patients with lesional tenderness, joint pains, and/or high fever. Relief of these subjective symptoms occurred within twenty-four hours. The possible mode of the action of potassium iodide and pathogenesis of erythematous dermatoses were also discussed.     

Type II lepra reaction: an unusual presentation

Ulcers with maculo-papular rash are an unusual presenting feature of leprosy. They occur as result of neuropathy, type-2 lepra reaction or Lucio's phenomenon. The hall mark of type-2 reaction is erythema nodosum. Very rarely it manifests as ulcerative skin lesions. We describe one such unusual case of a young male who presented with multiple ulcers and maculo-papular rash over the legs, chest and abdomen. In addition to this, he had fever, heart murmur, pulmonary infiltrates, neuropathy, and deranged liver function. A clinical differential diagnosis of infective endocarditis and systemic nectrozing vasculitis was made. Skin biopsy showed dense inflammation with lepra bacilli consistent with type-2 lepra reaction.     

Allergic granulomatosis (Churg-Strauss syndrome)

Allergic granulomatosis is a rare life-threatening systemic disorder of unknown origin, which represents a variant of systemic necrotizing vasculitis affecting medium-sized arteries and venules. Histologically, allergic granulomatosis is characterized by vascular and extravascular necrotizing palisading granulomas with prominent eosinophilia (Churg-Strauss granulomas). The clinical criteria include atopy with severe allergic asthma, pronounced peripheral eosinophilia, and nodular infiltrates of the skin and internal organs (Churg-Strauss granulomas). The internal organs most commonly involved are the lungs, gastrointestinal tract and, less often, the peripheral nerves, heart, and kidneys. Associated symptoms include fever, arthralgias and skin rashes, such as erythema multiforme, necrotizing venolitis, fixed drug eruption, and urticaria. Allergic granulomatosis shares common features with Wegener's granulomatosis and polyarteritis nodosa and may be related to the latter condition; overlap syndromes are a well-known occurrence. Similar to the other manifestations of systemic necrotizing vasculitis, immune complexes have been detected in fresh lesions and are suspected of being the basic pathogenetic findings. The causative antigens are likely to be respiratory antigens. The prognosis of untreated allergic granulomatosis is poor (mortality of approximately 50% within the first year). Systemic corticosteroids and cyclophosphamide are effective; complete remissions following cyclophosphamide treatment have been reported.