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PubMed1993

[In vivo and in vitro detection of borrelia infection in morphea-like skin changes with negative Borrelia serology].

No decision has been made yet as to whether or not the origin of the circumscribed scleroderma (morphea) is spirochetal. We describe a morphea-like skin lesion that developed after a tick bite 10 years ago. The histological investigation showed sclerodermal characteristics and necrobiosis lipoidica of the granulomatous type as well. No antibodies directed against Borrelia burgdorferi could be detected absorbance by a flagellin ELISA or by Western blot analysis. The VDRL, TPHA and FTA absorbance test, Warthin-Starry staining, and cultivation of Borrelia from skin biopsies were negative. The application of a nested polymerase chain reaction (PCR), relying on a combination of flagellin-gene-specific primers, demonstrated for the first time the presence of Borrelia DNA in a morphealike skin lesion. Immunohistological examination of the skin by a monoclonal antibody directed against flagellin was positive. Furthermore, in vitro GM-CSF secretion and lymphocyte proliferation upon stimulation with Borrelia-antigen was elevated and decreased significantly after 3 weeks of treatment with tetracyclines. In this case PCR analysis, immunohistochemistry and cellular immune response confirmed an infection with Borrelia, although no serum antibodies against spirochetal antigens could be detected.

Adolescent↗

PubMed1987

Unique mosaicism in Prader-Labhart-Willi syndrome--a contiguous gene or aneuploidy syndrome?

A 16-year-old boy with Prader-Labhart-Willi syndrome (PLWS) had hypotonia, feeding difficulties, failure to thrive, strabismus and bilateral inguinal hernias with cryptorchidism during infancy followed by hyperphagia, marked early-onset obesity with insulin-dependent diabetes mellitus and necrobiosis lipoidica diabeticorum, short stature, hypogonadotropic hypogonadism and some of the facial characteristics of the individuals with the PLWS. IQ is estimated around 90. Cytogenetic studies showed mosaicism: 45,X, t(Y;15) with partial deletion 15 (15pter----15q12); 46,X, t(Y;15), dic (15)(15pter----15q12::15q12----15pter) and 47, X, t(Y;15), dic(15), dic(15). The dic(15) was bisatellited, NOR-positive on both arms and represented inv dup(15). Thus, the 2 lines with the dic(15) showed partial trisomy 15 (15pter----15q12) and partial pentasomy 15 (15pter----15q12), respectively. The cell line ratios were different in lymphocyte and fibroblast cultures. The unique cytogenetic findings in this patient, the reports of a variety of chromosome 15 aberrations in PLWS, as well as aberrations of other chromosomes, suggest that the condition is a contiguous gene syndrome rather than an aneuploidy syndrome.

Adolescent↗

PubMed1979

Annular elastolytic giant cell granuloma. A clinicopathologic study of five cases and a review of similar entities.

Five patients with annular lesions of the face, scalp, and other exposed surfaces were studied using the radial triple zone biopsy technic. Interestingly, one of the patients had necrobiosis lipoidica diabeticorum (NLD) and another had systemic sarcoidosis. Clinically, the lesions were annular patches with erythematous borders and hypopigmented centers. The histopathology of the lesions showed many multinucleated giant cells, (often with prominent asteroid bodies), histiocytes, lymphocytes, scattered epithelioid cells, total lysis of elastic tissue, no necrobiosis, and absence of both mucin and lipid. This entity can be differentiated from granuloma annulare (GA), NLD, and cutaneous sarcoidosis. It is identical with several previously described entities; we propose a more appropriate term: "annular elastolytic giant cell granuloma (AEGCG)."

Adult↗

PubMed1983

Episcleral and orbital pseudorheumatoid nodules.

Pseudorheumatoid nodules are subcutaneous necrobiotic granulomas that are histopathologically similar or identical to those seen with rheumatoid arthritis, granuloma annulare, necrobiosis lipoidica diabeticorum, and systemic lupus erythematosus. Although these nodules are most common in children, they are also seen in adults and are usually located on the extremities and scalp. Eyelid and eyebrow involvement is seen infrequently. We histopathologically verified episcleral and orbital pseudorheumatoid nodules in an adult with eyelid and eyebrow nodules. Pseudorheumatoid nodules must be included in the differential diagnosis of subconjunctival mass lesions that may concomitantly involve the orbit, episclera, and periocular region.

Adult↗

PubMed2006

[Differential diagnosis of rheumatoid granuloma].

Rheumatoid granuloma (RG) is histomorphologically defined as a subcutaneous palisading granuloma with central fibrinoid necrosis. Clinically, it presents as a nodule typically localized at pressure points near the joints. From the rheumatic pathological point of view, the main diagnostic challenge is the differentiation of RG from granuloma anulare, especially if clinical information on the site of removal, known diseases, duration of illness, medication and existing American College of Rheumatology (ACR) criteria are missing. Other granulomatous lesions, such as mycobacterial infections, foreign body granulomas, necrobiosis lipoidica or sarcoidosis, can be differentiated from RG by histopathological criteria or by additional examinations such as pathogen specification or PCR. An immunohistochemical marker for the differential diagnosis of granulomas is not yet available. Diagnosis is based on conventional H-E staining, alcian blue-PAS staining, polarizing analysis or PCR. In the following article, the most important granulomatous entities in the differential diagnosis of RG are introduced and the main diagnostic characteristics are discussed.

Arthritis, Rheumatoid↗

PubMed2003

Use of infliximab, an anti-tumor necrosis alpha antibody, for inflammatory dermatoses.

BACKGROUND: Infliximab is a monoclonal antibody against tumor necrosis factor alpha currently approved by the U.S. FDA for the treatment of Crohn's disease and rheumatoid arthritis. Recently, a controlled trial reported its effectiveness for psoriasis. OBJECTIVE: The object of our study was to evaluate the efficacy and safety of infliximab for inflammatory or autoimmune cutaneous disorders. METHODS: A retrospective chart review was performed for patients who received infliximab at the University of Miami, Cedars Medical Center. RESULTS: Patients with various disease, including panniculitis, pityriasis rubra pilaris, eosinophilic fasciitis, discoid lupus erythematosus, and necrobiosis lipoidica diabeticorum, received infliximab infusion at a dose of 5 mg/kg. All patients had refractory disease or adverse effects to previous therapy, which included cyclosporine, systemic steroids, azathioprin, clofazimine, mycophenolate mofetil, acitretin, UVB, and thalidomide. Six out of the seven patients improved after treatment. CONCLUSIONS: Infliximab was well tolerated in most patients and the majority benefited from the use of infliximab.

Adult↗

PubMedDate not supplied

An unusual cause of refractive chronic bilateral leg ulceration.

BACKGROUND: Ulceration of the lower extremities is a common disorder that can be very painful. It occurs most frequently in the elderly population as a result of venous hypertension. We report an unusual case of a 32-year-old man with an 11-year history of extensive, painful, bilateral leg ulcers resistant to conventional treatment necessitating above-knee amputation of the left leg. Eventually, the patient was treated with prednisone, which led to almost complete healing of the ulcers of the right leg. OBJECTIVE: The objective of this report is to discuss a rare cause of chronic bilateral leg ulceration. METHODS: Detailed histopathologic examination showed a complex pattern of overlapping features of several specific dermatologic conditions, including necrobiosis lipoidica (NL), necrobiotic xanthogranuloma (NXG), and the destructive form of granuloma annulare (GA). CONCLUSION: The characteristics of our patient suggest a variant of a cutaneous necrobiotic disorder that has not been previously reported. When clinicians are confronted with recalcitrant ulcerations in the lower extremity, this group of disorders should be considered in the differential diagnosis.

Adult↗

PubMed2005

Off-label dermatologic uses of anti-TNF-a therapies.

BACKGROUND: Tumor necrosis factor-alpha (TNF-a) is a proinflammatory cytokine that plays an immunomodulatory role in a variety of systemic and dermatologic diseases. Currently, three anti-TNF-a drugs are available in North America- infliximab (approved in the U.S. for the treatment of rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, ulcerative colitis, and psoriatic arthritis), etanercept (approved in the U.S. for the treatment of rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and psoriasis), and adalimumab (approved for the treatment of rheumatoid arthritis and psoriatic arthritis). OBJECTIVE: To review the current literature supporting alternative (and currently off-label) dermatologic uses of TNF-a antagonists. METHODS: A MEDLINE search (1966-March 2005) was conducted using the keywords "infliximab," "etanercept," "adalimumab," "TNF inhibitors," and "off-label" to identify published reports of off-label dermatologic uses of TNF-a inhibitors. RESULTS: Anti-TNF-a therapies have been reported in the following dermatologic diseases: sarcoidosis, hidradenitis suppuritiva, cicatricial pemphigoid, Behçet's disease, pyoderma gangrenosum, multicentric reticulohistiocytosis, apthous stomatitis, Sneddon-Wilkinson disease, SAPHO syndrome, pityriasis rubra pilaris, eosinophilic fasciitis, panniculitis, Crohn's disease, necrobiosis lipoidica diabeticorum, dermatomyositis, and scleroderma. The vast majority of these reports are in the form of individual case reports and small case series. Only two published randomized controlled trials involving the off-label use of a TNF inhibitor were found. CONCLUSIONS: A growing number of published reports suggest that anti-TNF-a therapies may be effective in the treatment of numerous inflammatory skin diseases outside their currently approved indications.

Adalimumab↗

PubMed1993

Necrobiotic xanthogranuloma without periorbital lesions.

Cutaneous necrobiotic xanthogranuloma is rare and closely resembles widespread necrobiosis lipoidica. It is important to recognize this skin disorder because of its strong association with paraproteinemia and, in some cases, with a hematologic malignancy. We describe two patients with necrobiotic xanthogranuloma who are unusual in that they had no periorbital involvement, a feature previously believed to be diagnostic of this condition.

Aged↗

PubMed1995

Clofazimine: a review of its medical uses and mechanisms of action.

Clofazimine has been in clinical use for almost 40 years, but little is known of its mechanism of action. The primary indication for clofazimine is multibacillary leprosy, but it is useful in several infectious and noninfectious diseases, such as typical myocobacterial infections, rhinoscleroma, pyoderma gangrenosum, necrobiosis lipoidica, severe acne, pustular psoriasis, and discoid lupus erythematosus. Postulated mechanisms of action include intercalation of clofazimine with bacterial DNA and increasing levels of cellular phospholipase A2. Clinical experience, possible mechanisms of action, and side effects of clofazimine are summarized.

Clofazimine↗

PubMedDate not supplied

Leg ulcers: uncommon presentations.

Uncommon presentations like vasculitis or other immunologic causes and malignancy account for about 1% to 2% of patients suffering from leg ulcers. We focus on such uncommon leg ulcers including: cutaneous vasculitis causing cutaneous ulceration, other immunologic or metabolic cutaneous lesions such as pyoderma gangrenosum and necrobiosis lipoidica, and ulcers based on neoplastic etiology. A short description on leg ulcers in the tropics is also included. The described uncommon presentations of leg ulcers are typically difficult to diagnose and treat; it is a specialist's job to take care of patients with these types of ulcers. Multidisciplinary specialized wound healing concepts integrated in the national health care system, as an accepted expert function, is the ideal way to organize the wound healing area. Such a system would result in an earlier diagnosis and more sufficient treatment for patients with uncommon presentations of leg ulcers.

Adult↗

PubMedDate not supplied

Diabetes mellitus.

Dermatologic problems are common in diabetes, with approximately 30% of patients experiencing some cutaneous involvement during the course of their illness. Skin manifestations generally appear during the course of the disease in patients known to have diabetes, but they may also be the first presenting sign of diabetes or even precede the diagnosis by many years. The skin involvement can be autoimmune in nature, such as acanthosis nigricans, necrobiosis lipoidica, diabetic dermopathy, scleredema, and granuloma annulare, or infectious in the form of erythrasma, necrotizing fasciitis, and mucormycosis. Pharmacologic management of diabetes, in addition, can also result in skin changes, such as lipoatrophy and lipohypertrophy, at the site of injection of insulin, and oral antidiabetic agents can cause multiple skin reactions as adverse effects. The management of these cutaneous manifestations is tailored according to the underlying pathophysiology, but a tight control of blood glucose is a prerequisite in all management strategies.

Blood Glucose↗

PubMed2006

Granuloma annulare--a genetic disorder that sustain an incomplete foreign-body granuloma reaction.

Granuloma annulare (GA) is a common dermatosis characterized by an annular arrangement of erythematous papules, plaques, rarely nodules or patches. It is a type of non-infectious granuloma with unknown etiology. Hypothesis. The immune reaction always begins with the foreign-body granuloma formation. However, if during the process the antigen is recognized as too small the immune reaction stops the granuloma development. In the case of GA the dysfunctional control mechanism continues to sustain the granulomatous formation. Because the target does not exist anymore, the initiated process starts the "search" for a new target (circular spreading). Different histological and clinical presentations depends on which gene of the control mechanism is dysfunctional, while the distribution depends on the type of antigen and its distribution at the start of the immune reaction. The disappearance of GA after biopsy, that occurs in some cases, could be attributable to the specific defective gene involved (the biopsy can disrupt only some type of GA). So, new therapies for solitary GA formations could be directed to the disruption and creation of a new and healthy immune response from the point of disruption. A comparative analysis of the gene expression of GA and the foreign-body granuloma in the same patient, and GA among different patients could clarify which genes are involved in granulomatous formations. The cells affected by those genetic defects are probably histiocytes and lymphocytes (both always present in GA). Because of some similarity, necrobiosis lipoidica could also be a specific type of GA.

Foreign-Body Reaction↗

PubMed1988

Fractures due to severe generalised osteoporosis in a 44-year-old male with diabetes mellitus.

A 44-year-old Chinese male with a 7-year history of diabetes developed spontaneous fractures affecting the femur and distal tibia and fibula within a period of 4 months. Spontaneous rib fractures were also present. There was additional evidence of extensive tissue damage with retinopathy, proteinuria, necrobiosis lipoidica diabeticorum, peripheral neuropathy and autonomic neuropathy. Investigation confirmed the presence of generalised osteoporosis and showed no evidence of other metabolic bone disease or abnormal vitamin D metabolism. Mild hypogonadism was also present and investigation suggested a disturbance of hypothalamic-pituitary control of gonadal function. It is suggested that the severe generalised osteoporosis resulted from poorly controlled diabetes with a possible additional contribution from androgen deficiency secondary to the diabetes.

Adult↗

PubMed1986

Intracellular elastin in generalized granuloma annulare.

This report reviews thirteen cases of generalized granuloma annulare. The light and electron microscopic appearance of intracellular elastin particles in eleven of these cases is described. These bodies were also noted in deep granuloma annulare, elastosis perforans serpiginosa, and a small percentage of localized granuloma annulare. They were not found in necrobiosis lipoidica.

Adult↗

PubMed2002

Cutaneous manifestations of diabetes mellitus.

Diabetes is a common disease with many cutaneous manifestations encountered by dermatologists. Diabetes and the skin may be linked by association (e.g., necrobiosis lipoidica); infection; diabetic complication (e.g., neuropathic ulcer); or treatment reaction. Review of recent studies and reports focuses on pathogenesis and treatment of these many diabetic cutaneous changes.

Diabetes Complications↗

PubMed2002

Subcutaneous pseudomembranous fat necrosis: new observations.

BACKGROUND: Pseudomembranous fat necrosis is a peculiar manifestation of necrosis of adipose tissue characterized by formation of pseudocystic cavities lined by crenulated membranes. The underlying mechanism for the formation of pseudomembranes is unknown and numerous hypotheses have been proposed. Despite divergent interpretations, most authors consider necrotic fat cells to be the anatomic substrate for the formation of pseudomembranes. METHODS: A total of 341 panniculitides were reviewed for the presence of pseudomembranous fat necrosis. The specific diagnoses were established after correlation of all available clinical and laboratory data with the histopathology. Special attention was given to the time in the evolution of the disease when the biopsy was taken. Additional immunohistochemical studies were performed in 12 cases. RESULTS: Thirty of 341 cases of different types of panniculitides were found to show pseudomembranous fat necrosis, namely: 10 of 15 cases of sclerosing panniculitis (lipodermatosclerosis), 6 of 95 cases of erythema nodosum, 7 of 34 cases of traumatic panniculitis, 1 of 7 cases of lupus panniculitis, 1 of 20 cases of erythema induratum Bazin (nodular vasculitis), 1 of 9 cases of necrobiosis lipoidica, 1 of 4 cases of sclerotic lipogranuloma, 1 of 9 cases of infectious panniculitis (erysipelas), 1 of 2 cases of pancreatic panniculitis, and 1 of 4 cases of subcutaneous sarcoidosis. Pseudomembranous fat necrosis labelled strongly for the histiocytic markers CD68 and lysozyme. CONCLUSIONS: Our series provides data suggesting that pseudomembranous fat necrosis represents a dynamic process that varies according to the evolution of the lesion at the time of the biopsy. In biopsies taken from early foci of panniculitides pseudomembranes show vescicular or picnotic nuclei. Later, pseudomembranes retain their crenulated appearance but lack nuclear elements. Furthermore, we present histopathologic, histochemical, and immunohistochemical evidence that pseudomembranous fat necrosis results from the interaction of residual products of disintegrated fat cells and macrophages. Histiocytic markers such as CD68 and lysozyme may be used as reliable tools in order to detect pseudomembranes in panniculitides.

Adipose Tissue↗

PubMed2001

Panniculitis. Part I. Mostly septal panniculitis.

The panniculitides represent a group of heterogeneous inflammatory diseases that involve the subcutaneous fat. The specific diagnosis of these diseases requires histopathologic study because different panniculitides usually show the same clinical appearance, which consists of subcutaneous erythematous nodules on the lower extremities. However, the histopathologic study of panniculitis is difficult because of an inadequate clinicopathologic correlation, and the changing evolutionary nature of the lesions means that biopsy specimens are often taken from late-stage lesions, which results in nonspecific histopathologic findings. In addition, large-scalpel incisional biopsies are required. However, we believe that by obtaining appropriate biopsy specimens and with adequate clinicopathologic correlation, a specific diagnosis may be rendered in most cases of panniculitis. It must be accepted that all panniculitides are somewhat mixed because the inflammatory infiltrate involves both the septa and lobules; however, in general the differential diagnosis between a mostly septal and a mostly lobular panniculitis is straightforward at scanning magnification. Mostly septal panniculitides with vasculitis include leukocytoclastic vasculitis involving the small blood vessels of the septa; superficial thrombophlebitis resulting from inflammation and subsequent thrombosis of large veins of the septa; and cutaneous polyarteritis nodosa, which is a vasculitis involving arteries and arterioles of the septa of subcutaneous fat with few or no systemic manifestations. Often septal panniculitides with no vasculitis are the consequence of dermal inflammatory processes extending to the subcutaneous fat, such as necrobiosis lipoidica, scleroderma, subcutaneous granuloma annulare, rheumatoid nodule, and necrobiotic xanthogranuloma. However, in other cases, the inflammatory process is primarily located in the fibrous septa of the subcutis with or without involvement of the overlying dermis. The most frequently seen septal panniculitis is erythema nodosum, which, in fully developed lesions, is characterized histopathologically by Miescher's radial granulomas in the septa.

Adipose Tissue↗