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PubMed1982

Thalidomide: use and possible mode of action in reactional lepromatous leprosy and in various other conditions.

The literature concerning the use and possible mode of action of thalidomide in reactional lepromatous leprosy and in various other conditions is reviewed. Although it has no action against the leprosy bacillus, its value in the treatment of the adverse reactions in this type of leprosy is well established, many leprologists considering it to be superior to any other drug for this purpose. Its efficacy in actinic prurigo is also impressive, and there are reports suggesting benefit in discoid lupus erythematosus. By contrast, its reported action in a number of other conditions, including severe aphthous stomatitis, Behçet's syndrome, pyoderma gangrenosum, nodular prurigo, and postherpetic neuralgia, needs confirmation in a larger number of cases, backed in some instances by clinical trial. The mechanism of action of this drug may be related to (1) anti-inflammatory effects, particularly an inhibition of neutrophil chemotaxis, (2) immunosuppressive effects, or (3) effects on neural tissue. Furthermore, structure-activity studies may allow separation of these and other possible effects. This review is in no way intended to lend support to the indiscriminate use of a potentially hazardous drug in various diseases of unknown cause, but rather to draw attention to a number of conditions in which the drug has been found effective. The further judicious use of thalidomide or a nonteratogenic analogue, with careful observation of results, may contribute to knowledge of the underlying pathology in some of these conditions, and possibly also to the mechanism of action of the drug itself.

Anti-Inflammatory Agents↗
PubMed1986

Cutaneous manifestations associated with the presence of the lupus anticoagulant. A report of two cases and a review of the literature.

Two patients with the lupus anticoagulant exhibited unusual cutaneous manifestations. They both fulfilled four criteria for systemic lupus erythematosus and had experienced deep venous thrombosis. The first patient suffered from a leg ulcer that resembled a pyoderma gangrenosum. The second patient presented erythematous and purplish macules on the fingertips. The histologic studies showed only microthrombosis in the dermal vessels without vasculitis, although such lesions in systemic lupus erythematosus are usually attributed to vasculitis. The association of these cutaneous lesions with lupus anticoagulant has never been reported. It is likely that this association is not fortuitous. After a review of the literature, it seems possible to individualize a new syndrome characterized by the presence of a subgroup of antiphospholipid antibodies. Thrombosis, spontaneous abortions, neurologic manifestations, pulmonary hypertension, positive results of a Coombs' test, and thrombocytopenia can be included in this syndrome, which overlaps with systemic lupus erythematosus. Certain cutaneous symptoms are associated with the presence of lupus anticoagulant or other antiphospholipid antibodies: leg ulcers, distal cutaneous ischemia, widespread cutaneous necrosis, and livedo. They can be considered as the dermatologic manifestations of this syndrome.

Adult↗
PubMed1986

Autointoxication revisited.

The pustular dermatitis associated with small bowel bypass surgery and the cutaneous manifestations of inflammatory bowel disease are well known and generally assumed to be due to the absorption of microbial antigens from the bowel. Monomeric serum IgA is assumed to originate in the gastrointestinal tract, and circulating IgA immune complexes, as seen in dermatitis herpetiformis, should make us suspicious of a gastrointestinal tract source. These circulating immune complexes and perhaps polyclonal increases in serum IgA may be the result of minor perturbations of mucosal permeability or the failure of locally produced dimeric serum IgA to inactivate bacterial or dietary antigens. Such disparate entities as Reiter's syndrome, psoriasis, pyoderma gangrenosum, and ankylosing spondylitis, as well as the pustular eruptions of Behçet's syndrome, pustular psoriasis, and lithium therapy, may share this common pathogenesis.

Humans↗
PubMed1988

Disseminated pustular dermatosis in polycythemia vera. Relationship with neutrophilic dermatosis of myeloproliferative disorders: study of neutrophil function.

An unusual case of disseminated pustular eruption associated with polycythemia vera is described. This eruption can be included in the group of neutrophilic dermatoses of myeloproliferative disorders (pyoderma gangrenosum, Sweet's syndrome). A defect in superoxide anion (O2-) generation is detected. The fact that both the clinical condition and the neutrophil function improved with the use of dapsone suggests that the O2- generation defect may play a role in the pathogenesis of the eruption. From an evolutionary standpoint, the occurrence of a neutrophilic dermatosis in polycythemia vera could be an unfavorable sign of preleukemia.

Aged↗
PubMed1994

Cutaneous Wegener's granulomatosis: clinical, histopathologic, and immunopathologic features of thirty patients.

BACKGROUND: Wegener's granulomatosis (WG) is a systemic disease characterized by necrotizing granulomatous inflammation and vasculitis. Its cutaneous manifestations vary. OBJECTIVE: We reviewed and characterized the clinical, pathologic, and immunopathologic features of the specific cutaneous manifestations of WG and investigated the sensitivity and the specificity of anti-neutrophilic cytoplasmic antibody (c-ANCA) in the cutaneous manifestations of this disease. METHODS: A retrospective analysis was conducted of 244 cases of WG observed between 1988 and 1992. RESULTS: Skin involvement occurred in 14% of the patients and was more frequent in generalized WG. Skin lesions may be an early premonitory sign of renal disease. Necrotizing ulcerations resembling pyoderma gangrenosum were not uncommon. Leukocytoclastic vasculitis was the most common cutaneous pathologic pattern. Findings of c-ANCA were positive in 81% of patients with cutaneous WG. CONCLUSION: Skin involvement usually occurred at presentation with generalized disease. c-ANCA is a valuable adjunct to diagnosis and follow-up of WG.

Adolescent↗
PubMed2001

[Skin manifestations associated with myelodysplastic syndromes].

PURPOSE: Our purpose was to describe cutaneous manifestations associated with myelodysplastic syndromes. METHODS: Data from seven patients with cutaneous vasculitis (four cases), neutrophilic dermatosis (one case), relapsing polychondritis (one case), and possible erythema elevatum diutinum (one case) in association with myelodysplastic syndrome (refractory anaemia RA, RA with excess of blasts--RAEB-, RAEB in transformation RAEBt, chronic myelomonocytic leukaemia--CMML-), and analysis of the literature were reviewed. RESULTS: The cutaneous manifestations of myelodysplastic syndrome may or may not be specific, and may reveal hemopathy transformation. The cutaneous vasculitis are the most frequent and polymorphic. The relation with neutrophilic dermatosis is more specific; they are a spectrum of diseases including pyoderma gangrenosum, Sweet's syndrome, erythema elevatum diutinum (nuclear segmentation anomalies of neutrophils both in the skin and in the blood are a biological marker of the association). Relapsing polychondritis is significantly associated with myelodysplastic syndromes. Their pathogenesis are controversial. CONCLUSION: Early biopsy of cutaneous lesions in myelodysplastic syndromes is indicated. Analysis of blood cell count (and more bone marrow biopsy in relapsing polychondritis) is indispensable in these neutrophilic cutaneous or vasculitis diseases.

Adult↗
PubMed2003

[Eccrine squamous syringometaplasia and cytomegalovirus infection].

BACKGROUND: Eccrine squamous syringometaplasia has been reported in some cases as an Herpeviridae complication. We report a case of eccrine squamous syringometaplasia associated with a severe cytomegalovirus infection in an immunocompromised patient, and we discuss about potential viral or drug triggering factors. METHODS: A 22 years-old man was hospitalized in an intensive care unit for rejection of a renal graft associated with a disseminated cytomegalovirus infection. A papular and papulopustular eruption appeared on the trunk and the limbs. RESULTS: Histological examination of a skin sample showed eccrine squamous syringometaplasia, with evidence of cytomegalovirus genomic sequences using PCR. Two weeks later, the patient developed toxic epidermal necrolysis, with fatal issue. CONCLUSIONS: Eccrine squamous syringometaplasia is a rare condition, without specific clinical features. Numerous local affections have been reported to induce eccrine syringometaplasia (ulcer, scar, pyoderma gangrenosum, drug injection.), drugs (cytotoxic agents, non steroidal anti inflammatory therapies) and in cases of infection due to cytomegalovirus or herpes simplex virus. The potential implication of cytomegalovirus or foscarnet as triggering factors in our case is discussed. This observation and other similar reported cases lead to the conclusion that eccrine squamous syringometaplasia may be an underestimated complication of cytomegalovirus infections in immunocompromised patients.

Adult↗
PubMedDate not supplied

[Leukocytoclastic vasculitis and malignant hematologic diseases. (12 cases)].

We report 12 cases of leucocytoclastic vasculities associated with myelocytic (7 cases) or lymphocytic (5 cases) blood diseases. The clinical features, laboratory abnormalities and pathological findings are presented. In all cases a drug-induced and/or infective origin could be ruled out, and patients with cryoglobulinaemia were excluded. As in other cases found in the literature, in some patients vasculitis was present several weeks or months before the blood disease was discovered, while in others both conditions developed simultaneously or vasculitis appeared in the course of the blood disease. None of these three possibilities seemed to make the prognosis worse. The pathogenesis of the vasculitis-malignant blood disease association is uncertain. Immune complexes of tumoral origin undoubtedly have some responsibility, but some deficiency of phagocytic cells or chemotactic factors also play a role. Cases such as ours enable the significance of vasculitis to be understood when it occurs in a patient with malignant blood disease, but above all they should prompt investigations for malignant blood disease in patients with cutaneous and/or systemic vasculitis, as is being done in patients with pyoderma gangrenosum or Sweet's syndrome.

Adult↗
PubMed2005

[When should a myeloproliferative syndrome be suggested in vascular medicine?].

Thrombotic events are frequent in polycythemia vera (PV) and in essential thrombocythemia (ET). The frequency of thrombotic complications at presentation of PV and ET is nearly 50%. The spectrum of thrombotic complications is broad: thrombosis of arteries, veins and microvessels have been reported. Venous thrombosis can involve all territories but PV and TE are the commonest underlying etiology for Budd-Chiari Syndrome and splanchnic veins thrombosis. Endogenous erythroid-colony formation may be seen in up to 78% of patients thought to have Budd Chiari Syndrome and in 48% of splanchnic veins thrombosis. Major arterial thrombotic complications occur in 20%, especially in the extremities and in cerebral circulation. Microcirculatory disturbances are common in ET, occurring in 29% at presentation and 27% during follow up. In the extremities, erythromelalgia, a characteristic syndrome of red and congested extremities with raised temperature and painful burning sensations, is noticed in 30 to 50% of TE. Other microcirculatory manifestations like acrocyanosis, blue toes, digital gangrene can occur. All of these manifestations are highly sensitive to aspirin. Cerebral microcirculatory symptoms occur in about one-third of patients: migraine, transient visual symptoms like scotomata, blurred vision are characterized by a sudden onset, a short duration and a sequential course. Three kinds of leg ulcers have been described: leg ulceration as a consequence of microcirculatory thrombosis, exceptionally, pyoderma gangrenosum, and leg ulcers attributed to side effects of hydroxyurea. Microcirculatory leg ulcers are the most common: they are painful, inflammatory and sometimes, necrotic. They heal with treatment of SMP. Hydroxyurea-induced leg ulcers are painful, fibrous and multiple in 60%. Cessation of hydroxyurea typically leads to wound healing. The Polycythemia Vera Study Group (PVSG) established diagnostic criteria for PV and TE. Because SMP can have incompletely expressed disease, other authors have proposed determination of serum erythropoietin, examination of bone marrow histology, and spontaneous endogenous colony assays for diagnosis of PV or TE. The individual thrombotic risk depends on elevated hematocrit for PV, age (> 60) and prior thrombosis for PV and TE. Congenital and acquired (antiphospholipid syndrome) thrombotic states probably increase the risk of thrombosis.

Humans↗
PubMed2000

Cutaneous infection due to Mycobacterium kansasii.

A patient presented with chronic leg ulcers after a mowing accident. He received several courses of antibiotics for presumed cellulitis, underwent surgical debridement, and was treated empirically with cyclosporin for presumed pyoderma gangrenosum, all without improvement. Cultures from prior debridement revealed Mycobacterium kansasii, and he was successfully treated with triple antituberculous regimen. Cutaneous infections due to this slow growing Mycobacterium are rare and may resemble cellulitis or sporotrichosis. Mycobacterium kansasii should be included in the differential diagnosis of skin infections with an indolent course and lack of response to antibiotics.

Adult↗
PubMed1997

Pediatric dermatology.

The latest studies regarding the controversial and concerning subjects of pigmented nevi and melanoma in children are reviewed. Additional topics covered include dermatologic conditions that feature genetic mosaicism, theories of pathogenesis of Langerhans cell histiocytosis, new clinical information regarding juvenile xanthogranulomas, and the unique features of pyoderma gangrenosum in infants and children.

Age of Onset↗
PubMed1987

Seronegative arthropathies in the foot.

It has been seen that involvement of the foot in the seronegative arthropathies forms a regular and varied part of the clinical picture. This is often quite different from that seen in rheumatoid arthritis; its components, whether in joints, periarticular structures, or as surface manifestations, may be characteristic enough to raise the diagnosis of 'spondarthritis'. The features described, though characteristic of the spondarthritides, are, however, not pathognomonic. Thus, the osteolysis in psoriatic arthritis also occurs in neuropathic arthritis (e.g. syringomyelia, leprosy), psoriatic periosteal changes may mimic osteosarcomatous proliferations, and the calcaneal enthesitis so typical of spondylitis, Reiter's disease and psoriatic arthritis, may also be seen in metabolic arthropathies. It should also be mentioned here that the severe erosive osteolytic changes leading to psoriatic arthritis mutilans may also be seen, albeit rarely, in rheumatoid arthritis. Ankylosis, too, is not totally confined to the spondarthritides, having also been reported in occasional patients with rheumatoid arthritis. Calcaneal erosions, sometimes envisaged as a spondarthritic feature, also occur in rheumatoid patients. Within the spondarthritis matrix, a striking overlap is seen in the pattern of arthritis. Thus, involvement of the feet in psoriatic arthritis and in Reiter's disease shows many similarities, particularly the tendency to involve IP joints in asymmetrical oligoarticular fashion. In the hindfoot, too, parallels can be drawn between the tendency to Achilles and plantar insertion enthesitis in ankylosing spondylitis and Reiter's disease. On the other hand, the arthropathies of the chronic inflammatory bowel diseases, ulcerative colitis, Crohn's disease, and Whipple's disease, share with Behçet's syndrome an asymmetrical involvement of knees and ankles, but relative freedom from foot involvement. Regarding the surface features in the foot of spondarthritides, there is overlap here, too. For example, the nail dystrophy of psoriasis can be indistinguishable from that of Reiter's disease, and pustular psoriasis in its severe form cannot be differentiated from keratoderma blenorrhagica, even at the histological level. Other surface manifestations affecting the lower limb in general distribution may spread to the feet and thus fall within the ambit of this discussion. Such features include the lesions of erythema nodosum, patches of pyoderma gangrenosum, and the tender cords of thrombophlebitis, all of which have a higher prevalence in seronegative arthritis than in seropositive disease.(ABSTRACT TRUNCATED AT 400 WORDS)

Arthritis↗
PubMed1999

Changes in bacterial enzymes and PCR profiles of fecal bacteria from a patient with ulcerative colitis before and after antimicrobial treatments.

A 26-year-old female patient, suffering from recurrent attacks of ulcerative colitis accompanied by extraintestinal symptoms (erythema nodosum and pyoderma gangrenosum), was evaluated for the effect of antibacterial agents on the intestinal bacteria and their enzymatic activities. The enzymes were assayed both at the onset of disease symptoms and after treatment with each of five drug regimens (fluconazole and cefadroxil, cefuroxime axetil and cestriaxone sodium, ciprofloxacin and cestriaxone sodium, ciprofloxacin alone, and ciprofloxacin, metronidazole, and cephalexin). The activities of azoreductase, nitroreductase, oxidoreductase, glucuronidase, and sulfatase were generally lower following all of the treatments, especially when ciprofloxacin was included. The DNA from each sample was amplified by PCR, using random primers. Profiles of amplified DNA on agarose gels showed different patterns, indicating differences in the microflora before and after the antimicrobial treatments. The clinical response to antibacterial therapy was consistent with the decreased bacterial enzymatic activities and changes in the microbial population. Ciprofloxacin, which was associated with the most dramatic falls in enzymatic activity, also had the best clinical results. We conclude that intestinal bacteria and their enzymes play important roles in ulcerative colitis and that population changes can be monitored using PCR profiles.

Adult↗
PubMed2002

[Skin manifestations of diseases of the gastrointestinal tract].

Diseases of the gut frequently show skin symptoms. These can give first and important clues in regard to diagnosis. In general the etiology can be divided into genetic disorders, chronic inflammation, drug reaction, infectious diseases or related to malignancy. In genetic disorders increasing knowledge about the involved genes is available, allowing prenatal diagnosis and screening of clinically not affected family members. Especially in cancer prone syndromes early diagnosis and preventive treatment is crucial. Inflammatory bowel diseases show a high prevalence, therefore necessitating the knowledge of skin complications such as pyoderma gangrenosum, Sweet syndrome and erythema nodosum. Gastrointestinal malignancies may metastasize into the skin or may produce typical paraneoplastic changes.

Diagnosis, Differential↗
PubMed2002

Tacrolimus enhances irritation in a 5-day human irritancy in vivo model.

Tacrolimus (FK 506) is a macrolide discovered in 1984 as a metabolic product of Streptomyces tsukabaensis. It has been used successfully in treating atopic dermatitis, allergic contact dermatitis, lichen planus mucosae and pyoderma gangrenosum. In the present study, we evaluated the anti-inflammatory activity of FK 506 in 2 human skin inflammation models. FK 506 as Protopic(R) cream was tested (i) in a 4-day repetitive irritation test with 2 x daily application of sodium lauryl sulphate (SLS), and (ii) in a UVB erythema model. The effect was evaluated visually and quantified by non-invasive bioengineering methods, namely chromametry and tewametry (TEWL). When FK 506 was applied 30 min after SLS irritation, an increased inflammation in comparison to controls was observed with all 3 methods, with only the TEWL data reaching statistical significance. 1 x daily application of FK 506 for 5 days, starting at the end of the 4-day irritation period, was without any effect. Similarly, no effect of FK 506 was seen in the UVB model. In conclusion, FK 506 was shown to enhance experimentally induced irritant contact dermatitis and not to accelerate healing of irritant contact dermatitis and UVB erythema.

Adult↗
PubMed2003

The spectrum of cutaneous lesions in rheumatoid arthritis: a clinical and pathological study of 43 patients.

INTRODUCTION: Rheumatoid arthritis (RA) is an idiopathic arthropathy syndrome that has a propensity to affect the small joints of the hands and feet with extra-articular manifestations comprising skin lesions, neuropathy, pericarditis, pleuritis, interstitial pulmonary fibrosis and a systemic polyarteritis nodosa (PAN)-like vasculitic syndrome. The most widely recognized skin lesion is the rheumatoid nodule. Other skin manifestations are poorly defined. MATERIALS AND METHODS: Using a natural language search of the authors' outpatient dermatopathology databases, skin biopsies from 43 patients with RA were selected for retrospective analysis in an attempt to define the dermatopathological spectrum of RA and its clinical correlates. RESULTS: The biopsies were categorized by the dominant histologic pattern, recognizing that in most cases there were additional minor reaction patterns. Palisading and/or diffuse interstitial granulomatous inflammation was the dominant pattern seen in 21 patients; the lesions included nodules, plaques and papules with a predilection to involve skin over joints. Besides interstitial histiocytic infiltrates and variable collagen necrobiosis, these cases also showed interstitial neutrophilia, vasculitis and pauci-inflammatory vascular thrombosis. The dominant morphology in 11 other patients was vasculopathic in nature: pauci-inflammatory vascular thrombosis, glomeruloid neovascularization, a neutrophilic vasculitis of pustular, folliculocentric, leukocytoclastic or benign cutaneous PAN types, granulomatous vasculitis, and lymphocytic vasculitis and finally occlusive intravascular histiocytic foci for which the designation of "RA-associated intravascular histiocytopathy" is proposed. Rheumatoid factor (RF) positivity and active arthritis were common in this group, with anti-Ro and anticardiolipin antibodies being co-factors contributing to vascular injury in some cases. Immunofluorescent testing in three patients revealed dominant vascular IgA deposition. In nine patients, the main pattern was one of neutrophilic dermal and/or subcuticular infiltrates manifested clinically as urticarial plaques, pyoderma gangrenosum and panniculitis. CONCLUSIONS: The cutaneous manifestations of RA are varied and encompass a number of entities, some of which define the dominant clinical features, such as the rheumatoid papule or subcutaneous cords, while others allude to the histopathology, i.e. rheumatoid neutrophilic dermatosis. We propose a more simplified classification scheme using the adjectival modifiers of "rheumatoid-associated" and then further categorizing the lesion according to the dominant reaction pattern. Three principal reaction patterns are recognized, namely extravascular palisading granulomatous inflammation, interstitial and/or subcuticular neutrophilia and active vasculopathy encompassing lymphocyte-dominant, neutrophil-rich and granulomatous vasculitis. In most cases, an overlap of the three reaction patterns is seen. Co-factors for the vascular injury that we believe are integral to the skin lesions of RA include RF, anti-endothelial antibodies of IgA class, anti-Ro and anticardiolipin antibodies.

Adult↗
PubMed2006

Lessons learned from psoriatic plaques concerning mechanisms of tissue repair, remodeling, and inflammation.

Following injury, skin establishes a balance between too little inflammation increasing risk of infection, and excessive inflammation contributing to delayed wound healing and scarring. Mounting evidence indicates both initiation and termination of inflammation involve active mechanisms. Not only does inflammation itself seem to be a paradox because inflammatory responses are both essential and potentially detrimental, but one chronic inflammatory skin disease (e.g. psoriasis) presents additional paradoxes. While plaques share several factors with wound healing, two understudied and puzzling aspects include why do not inflamed plaques more frequently transform?; and why do not plaques result in scarring? To get at these questions, we review responses involved in wound repair. Oral mucosa was probed because, like fetal skin, wound repair is characterized by its rapidity, low inflammation, and scarless resolution. Active roles for macrophages as both initiators and terminators of inflammation are highlighted. Therapeutic implications are discussed regarding psoriasis and pyoderma gangrenosum. Based on biochemical and immunohistochemical considerations linking psoriatic plaques to hard palate, a novel metaplastic model is presented. We hypothesize saliva and chronic trauma contribute to a constitutive epithelial program where keratinocyte proliferation is more intense prior to differentiation, accompanied by keratin 16 expression in hard palate, thereby resembling plaques. Rather than viewing psoriasis as a nonspecific response to inflammation, we postulate a metaplastic switch by which prepsoriatic skin is converted to a distinct adult tissue type resembling hard palate. In summary, many lessons can be learned by focusing on complex processes involved in regulation of inflammation, tissue repair, and remodeling.

Fibrosis↗
PubMed2002

Chronic pruritic neutrophilic eccrine hidradenitis in a patient with Behçet's disease.

Neutrophilic eccrine hidradenitis (NEH) is a rare distinct entity that usually presents as asymptomatic erythematous papules that disappear spontaneously in 1-3 weeks. However, its appearance may be polymorphic, pruritic, recurrent or even chronic as is described in this case. The histological combination of neutrophilic infiltration in and necrosis of the eccrine secretory gland epithelium is highly characteristic for NEH. It typically occurs in patients receiving chemotherapeutic drugs for malignancies, but other associations have also been reported. To our knowledge, we report the first case of NEH in a patient with Behçet's disease (BD). Cutaneous manifestations of BD, an inflammatory systemic disorder of unknown origin, include neutrophilic dermatoses such as Sweet's syndrome and pyoderma gangrenosum, although these are unusual in BD. NEH could be another neutrophilic dermatosis related to BD. This observation suggests that NEH is not strictly related to chemotherapeutic drugs and malignancies. It appears to be a reactive dermatosis associated with other factors as well, including BD. Treatment was successful with dapsone 100 mg daily.

Anti-Inflammatory Agents, Non-Steroidal↗