Cutaneous manifestations of inflammatory bowel disease: basic characteristics, therapy, and potential pathophysiological associations.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease typically involving the gastrointestinal tract but not limited to it. IBD can be subdivided into Crohn's disease (CD) and ulcerative colitis (UC). Extraintestinal manifestations (EIMs) are observed in up to 47% of patients with IBD, with the most frequent reports of cutaneous manifestations. Among these, pyoderma gangrenosum (PG) and erythema nodosum (EN) are the two most common skin manifestations in IBD, and both are immune-related inflammatory skin diseases. The presence of cutaneous EIMs may either be concordant with intestinal disease activity or have an independent course. Despite some progress in research on EIMs, for instance, ectopic expression of gut-specific mucosal address cell adhesion molecule-1 (MAdCAM-1) and chemokine CCL25 on the vascular endothelium of the portal tract have been demonstrated in IBD-related primary sclerosing cholangitis (PSC), little is understood about the potential pathophysiological associations between IBD and cutaneous EIMs. Whether cutaneous EIMs are inflammatory events with a commonly shared genetic background or environmental risk factors with IBD but independent of IBD or are the result of an extraintestinal extension of intestinal inflammation, remains unclear. The review aims to provide an overview of the two most representative cutaneous manifestations of IBD, describe IBD's epidemiology, clinical characteristics, and histology, and discuss the immunopathophysiology and existing treatment strategies with biologic agents, with a focus on the potential pathophysiological associations between IBD and cutaneous EIMs.

Idiopathic granulomatous mastitis associated with erythema nodosum may indicate a worse prognosis.

INTRODUCTION: Idiopathic granulomatous mastitis (IGM) is a chronic inflammatory breast disease of unknown etiology, and erythema nodosum (EN) is a rare extramammary manifestation of this entity characterized by reddish, tender nodules of the lower legs. We aimed to investigate whether the association of IGM with EN has a role as a prognostic indicator. There are few case reports, and only 1 original article including 12 IGM patients with EN has been reported. METHODS: We present 43 women with IGM coexisting with EN and 43 with a diagnosis of IGM only, who were randomly selected from 610 patients for a control group. To the best of our knowledge, this paper comprises the first comparative study of the coexistence of IGM and EN to be reported in the literature. RESULTS: Our findings show that the association of IGM with EN indicates a more aggressive disease course. White blood cells, erythrocyte sedimentation rate, and C-reactive protein were significantly higher in the EN-positive group (P < .05). Arthralgia, breast feeding, fistula distribution and recurrence distributions were significantly higher in the EN-positive group (P < .05). CONCLUSION: Since fistula distribution and recurrence rates were higher in EN-positive group, association of IGM with EN may be an indictor of a worse prognosis. The present study highlights the importance of dermatological care. All physicians should not neglect questioning breast complaints in patients with EN since EN may be caused by IGM.

Paraprotein associated syndrome treated successfully with chemotherapy.

We report a 50-year-old Caucasian woman who presented with recurrent erythema nodosum, leg swelling, malaise, weight loss and abdominal pain associated with an IgM lambda paraprotein. She was treated with six courses of an anti-CD20 monoclonal antibody and bendamustine chemotherapy over 6 months with a good clinical response.

Erythema nodosum in a patient with multiple sclerosis on dimethyl fumarate.

Erythema nodosum is an uncommon cutaneous hypersensitivity reaction characterized by tender round slightly raised red nodules that become bruise-like and then resolve without scarring. It may be caused by infections, pregnancy, malignancy, systemic illnesses, or idiopathic. Several drugs have been reported in association with erythema nodosum including oral contraceptive pills, penicillin, and sulphonamides. Glatiramer acetate is the only medication used in the treatment of multiple sclerosis that has been reported as a possible cause of erythema nodosum. The association between erythema nodosum and multiple sclerosis or dimethyl fumarate has not been reported in the literature. In this article, we aim to report the first case of a possible association between erythema nodosum and dimethyl fumarate in a multiple sclerosis patient. We hypothesize that dimethyl fumarate may be the cause for the development of erythema nodosum in our patient. The underlying mechanism a possibly related to a delayed hypersensitivity reaction.

Erythema nodosum.

BACKGROUND: Erythema nodosum can be associated with a number of systemic diseases. There is, however, a paucity of information in the pediatric literature on this condition. The purpose of this article is to familiarize pediatricians with the evaluation, diagnosis, and treatment of erythema nodosum. DATA SOURCES: A PubMed search was completed in Clinical Queries using the key terms "erythema nodosum". RESULTS: Clinically, erythema nodosum presents with a sudden onset of painful, erythematous, subcutaneous nodules mainly localized to the pretibial areas. Lesions are usually bilateral and symmetrical, ranging from 1 to 5 cm in diameter. Erythema nodosum may be associated with a variety of conditions such as infection, medications, sarcoidosis, pregnancy, inflammatory bowel disease, vaccination, autoimmune disease, malignancy, and miscellaneous causes. The condition is idiopathic in approximately 50% of cases. The diagnosis is mainly clinical with biopsy reserved for atypical cases. To evaluate for the underlying cause, some basic laboratory screening studies are worthwhile in most cases and include a complete blood cell count, erythrocyte sedimentation rate and/or C-reactive protein, throat swab culture, antistreptococcal O titers, and a chest radiograph. Other tests should be individualized, guided by the history and physical examination results. Most cases of erythema nodosum are self-limited and require no treatment. Bed rest and leg elevation are generally recommended to reduce the discomfort. Nonsteroidal anti-inflammatory drugs are the first-line treatment for pain management. CONCLUSIONS: As erythema nodosum is often a cutaneous manifestation of a systemic disease, a thorough search should be performed to reveal the underlying cause.

Lepra dimorfa lepromatosa conyugal / Lepromatous dimorphic leprosy in spouses

Leprosy is a contagious, chronic infectious disease caused by Mycobacterium leprae. The immune response of the host to this bacillus is variable, determining different clinical forms of the same disease. Between the Lepromatous and Tuberculoid spectra, both stable clinical forms, the Dimorfo type can be presented, with great immunological instability, determining clinical characteristics, according to the pole to which most approaches. Leproatous dimorphic leprosy is characterized by brwn and violet macules, large number of lesions and less definition at its edges, variable sizes and alteration of sensitivity. Conjugal leprosy occurs in very few cases, knowing that intimate contaqct for a long time is an important factor, but has also demonstrated the fundamental role of immunity and genetics to acquire and develop the disease. We present two cases of lepromatous dimorphic leprosy in spouses, with 20 years of cohabitation, in which the same clinical presentation was found. Ths is an infrequent fact, given the low infectivity of the pathogen and the multiple varieties that could occur.

Disease-related and drug-induced skin manifestations in inflammatory bowel disease.

INTRODUCTION: Skin manifestations are common in patients with inflammatory bowel diseases (IBD) and can be part of a concomitant illness with a shared genetic background, an extra-intestinal manifestation of the disease, or a drug side-effect. Areas covered: We provide a practical overview of the epidemiology, pathogenesis, diagnosis, therapeutic approach and prognosis of the most frequent disease-related and drug-induced cutaneous manifestations in IBD, illustrated by cases encountered in our clinical practice. Among the most frequently encountered IBD-related lesions are erythema nodosum, pyoderma gangrenosum and Sweet's syndrome. Common skin manifestations with a strong association to TNF antagonists are local injection site reactions, psoriasiform lesions, cutaneous infections, vasculitides and lupus-like syndromes. In addition, we discuss the relation of thiopurines and TNF antagonists with the risk of skin cancer. Expert commentary: We hope this review will help caretakers involved in the management of IBD patients to recognize the lesions and to manage them in close collaboration with a dedicated dermatologist.

Sarcoidosis aguda: variante de Síndrome de Lõfgren sin eritema nodoso / Acute sarcoidosis: erythema nodosum-free variant of Lõfgren’s Syndrome

El síndrome de Lõfgren, es una variante aguda de la sarcoidosis, que se caracteriza por fiebre, eritema nodoso, adenomegalias hiliares pulmonares y artritis. En general, tiene un curso benigno y autolimitado, que contrasta con las formas crónicas que requieren uso de corticoides y tienen tendencia a la recidiva. Se describe aquí el caso clínico de un paciente joven, de sexo masculino, con artritis pero sin eritema nodoso, lo que dificultó el planteo diagnóstico de síndrome de Lõfgren. Se realiza además una breve descripción comparativa entre la presentación clínica de la sarcoidosis crónica y el síndrome de Lõfgren...

[Effect of Immunovac-VP-4 and Kagocel immunotherapy on cytokine levels in patients with erythema nodosum].

Fixed erythema--a kind of clinical and histopathologic reaction, fixed drug eruption. The purpose of the study--the study of characteristics of the cytokine profile in patients with erythema and the dynamics of the basal levels of proinflammatory and antiinflammatory cytokines during immunotherapy. All 41 patients with fixed erythema at baseline and after treatment was carried out determination of levels of pro-, anti-inflammatory and regulatory cytokines in the serum by ELISA using test systems "Biosource" (Austria). In patients with fixed erythema Immunovac treatment increased serum IFN-gamma (p < 0.05), IL-1beta (p > 0.05), IL-6. While Kagocel led to an increase in IFN-gamma (p < 0.05), IL-1beta, IL-6 and reduction of TGF-beta (p < 0.05). At the same time in patients with fixed erythema basic therapy contributed to the significant increase in TGF-â and decrease in IL-10. Immunovac-VP-4 had the highest activity for the induction of IFN-gamma. Inclusion in the range of therapeutic and prophylactic measures in patients with fixed erythema immunomodulators promotes activation links innate and adaptive immunity triggers mechanisms, thus increasing the antiviral response in patients with erythema.

Panniculitis in children.

This paper will give a comprehensive view of the most frequent panniculitides seen in childhood, with emphasis on the types exclusively found in infancy, and for all other types of panniculitides also found in adults. Aim of this paper is also to analyze the clinical differences between panniculitis in childhood and in adulthood, and to give reliable histopathologic criteria for a specific diagnosis. A review of the literature is here integrated by authors' personal contribution. Panniculitides in children is a heterogeneous group of diseases, as well as in adult life, characterized by inflammation of the subcutaneous fat. Only very few types of panniculitis are exclusively found in childhood, such as Sclerema neonatorum and subcutaneous fat necrosis of the newborn, while the vast majority of the other types may be found both in paediatric age and in adults. Furthermore, this paper will consider in detail panniculitis according to their frequency, such as Erythema nodosum, Lupus panniculitis, Cold panniculitis, panniculitis in Behçet disease, and poststeroid panniculitis. It will also describe rare forms of panniculitis, such as Eosinophilic panniculitis (a pathological entity debated by many authors), Subcutaneous panniculitis T-cell lymphoma, and the different forms of the so call "Lipophagic panniculitis", encompassing respectively the febrile relapsing panniculitis of Weber-Christian disease and the non-relapsing form of Rothmann-Makai disease. For each type of panniculitis considered concise information will be given about epidemiology, etiology, clinical findings, laboratory data, prognosis and therapy, while histopathologic findings will be described in detail.

Etiology and therapeutic management of erythema nodosum during pregnancy: an update.

Erythema nodosum (EN) is the most common form of panniculitis. It is characterized by erythematous, raised, tender nodules that usually occur bilaterally on the extensor surfaces of the lower extremities. EN is associated with many underlying conditions including infection, sarcoidosis, malignancy, and pregnancy. Its underlying etiology, however, is unknown in up to half of cases. Pregnancy is thought to create an optimal background for EN to develop, although the exact mechanisms are unclear. Immune complexes may play a role in the pathogenesis of EN during pregnancy, or EN may be a hypersensitivity reaction to either estrogens or progesterone. EN is a self-limiting process, and non-pharmacologic means such as bed rest and elastic web bandages may be sufficient to control the symptoms. Potassium iodide, systemic and intralesional corticosteroids, non-steroidal anti-inflammatory drugs, salicylates, tumor necrosis factor-α inhibitors, hydroxychloroquine, colchicine, and dapsone are other treatment options available, but some of these drugs are contraindicated in pregnancy while others are considered safe. Before prescribing one of these treatments to a pregnant patient, the patient's obstetrician should be consulted, and a careful risk-benefit analysis should be performed.

Cutaneous sarcoidosis.

Sarcoidosis is a systemic disease with skin manifestations. Skin manifestations are classified as nonspecific if they are not characterized by granulomatous inflammation and specific if the lesions have granulomas histologically. Erythema nodosum is the most common nonspecific skin manifestation, and it portends a good prognosis. Specific skin lesions have a varied clinical appearance, although often they can be distinguished by their yellow translucent character. Despite the potential variable appearance, there are common clinical presentations. Lupus pernio lesions are nodular violaceous specific skin lesions found predominantly on the face associated with scarring and a poor prognosis. Treatment of cutaneous sarcoidosis is primarily done to avoid scarring and cosmetic disfigurement. Local and systemic corticosteroids are the mainstay of treatment for the disease. Corticosteroid-sparing agents used to manage the disease include antimalarials, methotrexate, and tetracycline antibiotics. Tumor necrosis factor-alpha (TNF-alpha) antagonists such as infliximab may have a role in cutaneous sarcoidosis, especially in refractory cases that are resistant to the standard regimens.

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.

[Episcleritis and erythema nodosum in a patient with ulcerative colitis].

A 62-year-old Japanese woman with ulcerative colitis (UC) had episcleritis and erythema nodosum. Oral administration of corticosteroid with granulocytapheresis improved all these diseases. Extraintestinal manifestations such as ocular and skin complications are infrequent, especially in Japan, in patients with UC. Although concurrent onset of episcleritis and erythema nodosum associated with UC is also extremely rare, clinical course in this case suggests a possible association among ulcerative colitis, episcleritis and erythema nodosum.

Erythema nodosum: an evaluation of 100 cases.

OBJECTIVES: In this study, we investigated the clinical features, etiology, and also predictive factors of secondary erythema nodosum (EN) in patients with EN. METHODS: A total of 100 patients (mean age: 37 years) diagnosed with EN between 1993 and 2004 in our clinic were included in the study prospectively. A skin biopsy was performed in 46 of the patients. Patients were considered to have secondary EN when an underlying condition was found, and to have primary EN when no such condition was found. For the diagnosis of the underlying diseases, the pertinent diagnostic criteria and/or diagnostic methods were used. Categorical and continuous variables were compared by using chi-square and Mann-Whitney U tests respectively. Multiple regression analysis was applied to the significantly different variables. RESULTS: The majority of the patients were female (female/male: 6/1) and nearly half (47%) of the cases had a determined etiology. The leading etiology was poststreptococcal (11%), followed in decreasing order by primary tuberculosis (10%), sarcoidosis (10%), Behçet's syndrome (BS) (6%), drugs (5%), inflammatory bowel diseases (IBD) (3%), and pregnancy (2%). Fifteen (15%) patients complained of cough; the diagnosis was primary tuberculosis in eight cases and sarcoidosis in seven. Four patients with arthritis were diagnosed as having BS (in 3) and Crohn's disease (in 1). All the patients were followed for a mean duration of 4.5 years. The nodosities relapsed annually in 62% (33/53) of idiopathic EN patients but in only one (BS) in the secondary EN group. The histology was consistent with EN in all biopsied patients. Our study revealed that fever, leukocytosis, elevated CRP level, accelerated ESR, presence of cough, sore throat, diarrhea, arthritis, and pulmonary pathology were predictors of secondary EN. Recurrence in EN significantly predicted primary EN. All of the patients had bed rest and the majority was given an anti-inflammatory agent (naproxen sodium). The outcomes were usually favorable within 7 days. The patients with an underlying disease were given the specific treatment. CONCLUSION: EN has been associated with numerous diseases. In order to reduce cost and duration of diagnosis, every centre should determine its own most frequent etiologic factors. Predictive variables for secondary EN should also be determined and an optimum management for such patients should be clarified. Our study revealed streptococcal pharyngitis, primary tuberculosis, sarcoidosis, IBD, and BS as the main etiologies of EN.

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. Erythema nodosum typically manifest by the sudden onset of symmetrical, tender, erythematous, warm nodules and raised plaques usually located on the lower limbs. Often the lesions are bilaterally distributed. At first, the nodules show a bright red color, but within a few days they become livid red or purplish and, finally, they exhibit a yellow or greenish appearance, taking on the look of a deep bruise. Ulceration is never seen, and the nodules heal without atrophy or scarring. Histopathologically, erythema nodosum is the stereotypical example of a mostly septal panniculitis with no vasculitis. The septa of subcutaneous fat are always thickened and variously infiltrated by inflammatory cells that extend to the periseptal areas of the fat lobules. The composition of the inflammatory infiltrate in the septa varies with age of the lesion. In early lesions edema, hemorrhage, and neutrophils are responsible for the septal thickening, whereas fibrosis, periseptal granulation tissue, lymphocytes, and multinucleated giant cells are the main findings in late stage lesions of erythema nodosum. A histopathologic hallmark of erythema nodosum is the presence of the so-called Miescher's radial granulomas, which consist of small, well-defined nodular aggregations of small histiocytes arranged radially around a central cleft of variable shape. Treatment of erythema nodosum should be directed to the underlying associated condition, if identified. Usually, nodules of erythema nodosum regress spontaneously within a few weeks, and bed rest is often sufficient treatment. Aspirin, nonsteroidal antiinflammatory drugs, such as oxyphenbutazone, indomethacin or naproxen, and potassium iodide may be helpful drugs to enhance analgesia and resolution. Systemic corticosteroids are rarely indicated in erythema nodosum and before these drugs are administered an underlying infection should be ruled out.