Cutaneous Alterations Research Articles

Occurrence, distribution and population size of Malassezia pachydermatis on skin and mucosae of atopic dogs

Aim of the present study was to determine the distribution and quantification of Malassezia yeasts on a wide number of cutaneous sites in atopic dogs by means of a semiquantitative swab technique. A possible relationship between the presence of clinical signs and the occurrence and population size of yeasts was attempted. Forty-one privately owned atopic dogs of different age and breed were sampled. Results were expressed as colony forming units per swab. Malassezia colonies obtained from each plate were counted, scored and typed. All dogs yielded Malassezia pachydermatis from at least one skin area. Yeast population mean size by site was 6.98 (S.D. = 3.47) as compared to other body areas. The frequence of isolation was higher from interdigital areas (70.7%), ears (63.4%), nail folds (35.7%), mouth (33.3%), groin (30.9%), conjunctiva and axillae (23.8%), perineum and anus (19%), perianal glands (9.5%). Ears, anus, interdigital areas, perianal glands and groin yielded the largest mycotic amount. M. pachydermatis was the sole species of yeast to colonize canine skin in examined animals. No statistical correlation between the presence of cutaneous alterations and Malassezia isolation was detected. Highest scores were not exclusively found on affected areas, but also on lesion-free sites, demonstrating that atopic animals can be heavily colonized also in apparently healthy areas.

Safety and Toxicity of Sulfadoxine/Pyrimethamine

Plasmodium falciparum infection during pregnancy is strongly associated with maternal anaemia and low birth weight, contributing to substantial morbidity and mortality in sub-Saharan Africa. Intermittent preventive treatment in pregnancy with sulfadoxine/pyrimethamine (IPTp-SP) has been one of the most effective approaches to reduce the burden of malaria during pregnancy in Africa. IPTp-SP is based on administering >or=2 treatment doses of sulfadoxine/pyrimethamine to pregnant women at predefined intervals after quickening (around 18-20 weeks). Randomised, controlled trials have demonstrated decreased rates of maternal anaemia and low birth weight with this approach. The WHO currently recommends IPTp-SP in malaria-endemic areas of sub-Saharan Africa. However, implementation has been suboptimal in part because of concerns of potential drug toxicities. This review evaluates the toxicity data of sulfadoxine/pyrimethamine, including severe cutaneous adverse reactions, teratogenicity and alterations in bilirubin metabolism. Weekly sulfadoxine/pyrimethamine prophylaxis is associated with rare but potentially fatal cutaneous reactions. Fortunately, sulfadoxine/pyrimethamine use in IPTp programmes in Africa, with 2-4 treatment doses over 6 months, has been well tolerated in multiple IPTp trials. However, sulfadoxine/pyrimethamine should not be administered concurrently with cotrimoxazole given their redundant mechanisms of action and synergistic worsening of adverse drug reactions. Therefore, HIV-infected pregnant women in malaria endemic areas who are already receiving cotrimoxazole prophylaxis should not also receive IPTp-SP. Although folate antagonist use in the first trimester is associated with neural tube defects, large case-control studies have demonstrated that sulfadoxine/pyrimethamine administered as IPTp (exclusively in the second and third trimesters and after organogenesis) does not result in an increased risk of teratogenesis. Folic acid supplementation is recommended for all pregnant women to reduce the rate of congenital anomalies but high doses of folic acid (5 mg/day) may interfere with the antimalarial efficacy of sulfadoxine/pyrimethamine. However, the recommended standard dose of folic acid supplementation (0.4 mg/day) does not affect antimalarial efficacy and may provide the optimal balance to prevent neural tube defects and maintain the effectiveness of IPTp-SP. No clinical association between sulfadoxine/pyrimethamine use and kernicterus has been reported despite the extensive use of sulfadoxine/pyrimethamine and related compounds to treat maternal malaria and congenital toxoplasmosis in near-term pregnant women and newborns. Although few drugs in pregnancy can be considered completely safe, sulfadoxine/pyrimethamine - when delivered as IPTp - has a favourable safety profile. Improved pharmacovigilance programmes throughout Africa are now needed to confirm its safety as access to IPTp-SP increases. Given the documented benefits of IPTp-SP in malaria endemic areas of Africa, access to this treatment for pregnant women should continue to expand.

Cutaneous Vascular Alterations in Psoriatic Patients Treated with Cyclosporine

Videocapillaroscopy can be used to assess cutaneous microcirculation modifications in vivo, and therefore allows assessment of variations in the microvascular architecture in psoriatic subjects during treatment. The aim of this study was to observe and quantify the modifications of the superficial capillary bed in psoriatic plaques during treatment with cyclosporin A. Twelve patients with psoriasis vulgaris were treated with an initial dose of 4 mg/kg/day cyclosporin A over a period of 3 months with periodic clinical and capillaroscopic assessments. Clinical resolution of the lesions and a reduction in microcirculatory alterations was observed in 70% of patients, although none returned to a normal capillaroscopic pattern.

Nocardiose pulmonar e cutânea em paciente usuário de corticosteróide

Nocardiosis is a localized or disseminated infection caused by gram-positive bacteria of the genus Nocardia. The infection most commonly affects the lungs, skin and central nervous system. Nocardiosis principally occurs in individuals with cellular immunodeficiency and should be considered in the differential diagnosis when such individuals present respiratory, cutaneous or neurological alterations. Herein, we report a case of pulmonary and cutaneous nocardiosis in a patient receiving oral corticosteroids to treat bronchiolitis obliterans accompanied by organizing pneumonia of unknown origin. After long-term treatment with sulfamethoxazole-trimethoprim, the clinical and radiological profile improved.

Cutaneous manifestations of primary immunodeficiency diseases in children.

Primary immunodeficiency diseases (PIDs) are rare but include severe conditions found predominantly in children, Most PIDs have cutaneous manifestations that may be important as early diagnostic features. The purpose of this study was to determine the frequency and nature of cutaneous alterations associated with PIDs. This article is a cross-sectional study at the department of allergy and clinical immunology of children's medical center conducted between December 5, 2001 and April 20, 2002. The subjects included pediatric patients with a diagnosis of PID and dermatological diagnoses were made by a dermatologist. Two hundred and ten patients were studied They consisted of 68 cases of humoral deficiency, 22 cases of cellular and combined deficiencies, 57 cases of phagocytic defects and 63 cases of other PIDs. In 67 cases (31.8%) the cutaneous alterations preceded and were the basis for clinical immunological diagnosis. Overall cutaneous alterations were infections in 99 cases and eczematous dermatitis in 27 cases. Our findings support the results of other studies that most PIDs have cutaneous features which being their typical aspects are highly suggestive for the diagnosis of PIDs.

Mexoryl: Broad-Spectrum Ultraviolet a Photoprotection

The deleterious effects of long-wave (320–400 nm) ultraviolet (UV) radiation on human skin have been recognized for decades. Human exposure to UV radiation may induce skin pigmentation and sunburn, cutaneous connective tissue alterations (photoaging), immunosuppression, and the development of skin cancers. Public awareness campaigns on the need for photoprotection advocate the regular use of sunscreens. Consumer demand and an expanding knowledge of the adverse effects of UV exposure have fueled the continual development of novel sunscreen formulations. Two organic UV filters, terephthlylidene dicamphor sulphonic acid (Mexoryl SX, L'Oréal, Paris, France) and drometrizole trisiloxane (Mexoryl XL, L'Oréal), provide effective protection from UV irradiation and offer improved safety profiles in terms of protection from UVA radiation. This article details the photoprotective benefits of Mexoryl SX and Mexoryl XL.

Skin changes in pediatric transplant patients

The advent of organ transplantation identified a new group of diseases. Dermatologists are studying transplant-associated diseases along with the atypical behavior of already known dermatoses. Pediatric patients have been treated as an extension of adult population, but unique aspects of age required clarification. A prospective cohort was studied including patients from both genders up to 17 yr of age who were recipients of kidney, liver or BMT during 2003 in Porto Alegre, Brazil. Regular skin examinations were performed up to the sixth month after the procedure, and an analysis was determined by ID (i.e. = number of skin changes/number of patients-month x 100). Thirty-nine patients were examined: 20 were kidney transplant recipients; 11 were BMT recipients (10 autologous transplants and 1 allogeneic transplant); and 8 were liver transplant recipients. Skin changes result primarily from the use of medication (87.2). Individually, kidney transplant patients presented the highest ID of skin changes because of medications (104.1). BMT recipients presented the highest ID of alterations occurring on skin appendages (85.4) and liver transplant recipients had the highest ID of vascular changes (94.9). In conclusion, this study shows that cutaneous alterations in pediatric transplant recipients present some particularities not described in adult recipients, such as ichthyosiform xerosis in renal recipients and skin scaling with pellagroid appearance in bone marrow recipients. Also, dermatoses secondary to medication use were the main finding in pediatric population.

La piel como expresión de alteraciones neurológicas en el recién nacido

The skin is involved in many different genetic syndromes and diseases with multiple organ involvement. Neurodevelopmental disorders appear in many of these entities and knowledge of these cutaneous alterations may provide clues to their diagnosis. Recognizing these skin disorders in the newborn allows early identification of neonates with a biological risk of epilepsy and motor and/or cognitive disorders and enables them to be followed up. This helps to plan the management of these patients and, in many entities, to predict their natural history and provide genetic counseling to the family. This review examines the cutaneous signs that may provide important clues in the neonate that help to identify entities that carry a risk of neurodevelopmental disorders in the neonate.

Atteinte unguéale et infiltration sclérodermiforme du visage au cours d’une amylose systémique

Mucocutaneous involvement in systemic amyloidosis occurs in 29 to 40 p. 100 of cases. Nail abnormalities are infrequent in AL amyloidosis. We report an original case of AL amyloidosis associated with cutaneous and integument alterations and scleroderma-like infiltration of the face. A 73 year-old woman was hospitalized because of weight loss and asthenia. She had been treated 4 years earlier with chemotherapy for a IgG-type multiple myeloma with complete resolution of the underlying monoclonal gammapathy. Cutaneous examination showed nail dystrophy of all fingernails associated with scleroderma-like skin changes on the chin and lips. Histopathologic study of a chin biopsy confirmed the presence of amyloid deposits in the dermis. Laboratory data were normal, without signs of recurrence of multiple myeloma. We report an original case of a patient who developed two unusual cutaneous manifestations associated with AL amyloidosis. Moreover, there was no correlation between the severity of the cutaneous lesions and the extent of the underlying hematological disease.

Dermatomiositis amiopática juvenil y calcinosis

Juvenile dermatomyositis (JDM) is a chronic multisystemic disease. It is believed to be of autoimmune etiology and is characterized by the presence of vasculitis affecting striated muscle and skin. Clinical description consists of general symptoms (anorexia, weight loss, asthenia, fever), typical manifestations (muscular and cutaneous) and possible systemic alterations. We report the case of a 5-year-old boy diagnosed with JDM who presented difficulty in walking, inability to completely extend the right lower extremity and calcinosis 12 months after the development of incorrectly evaluated cutaneous alterations. We aim to highlight the importance of early diagnosis and treatment of this illness. Since the introduction of corticosteroid therapy, prognosis has improved but functional outcome still depends on the presence of calcinosis and muscular contractures.

Combined dermal exposure to permethrin and cis-urocanic acid suppresses the contact hypersensitivity response in C57BL/6N mice in an additive manner

Cutaneous exposure to the pyrethroid insecticide permethrin significantly suppresses contact hypersensitivity (CH) response to oxazolone in C57BL/6N mice. Additionally, cis-urocanic acid ( cUCA), an endogenous cutaneous chromophore isomerized to its active form following exposure to ultraviolet radiation, modulates cell-mediated cutaneous immune responses. This study describes cutaneous immune alterations following combined topical permethrin and intradermal cUCA exposure. Female C57BL/6N mice were administered 5, 50 or 100 μg cUCA daily for 5 consecutive days. CH was then evaluated by the mouse ear swelling test (MEST) response to oxazolone. Decreased responses of 52.3%, 76.3% and 76.3%, respectively, as compared to controls were observed. Then, mice were co-exposed to 5 μg cUCA daily for 5 days and 1.5, 5, 15, or 25 μL permethrin, on either day 1, 3 or 5 of the cUCA treatment to evaluate combined immunomodulatory effects of the two chemicals, or cUCA daily for 5 days followed by permethrin on day 3, 5, or 7 after the last cUCA injection to demonstrate prolonged immunosuppressive effects. Two days after final treatment, mice were sensitized with oxazolone and MEST was performed. Mice receiving five cUCA injections and permethrin topically on cUCA injection day 1 showed up to 93.3% suppression of MEST compared to vehicle control. CH was suppressed by 87.5%, 86.6% and 74.2% in mice treated with 25 μL permethrin on days 3, 5 and 7 after cUCA, respectively, compared to vehicle control. Taken together, these data indicate co-exposure to cUCA and permethrin profoundly suppresses cell-mediated cutaneous immunity.

Development of UV-induced squamous cell carcinomas is suppressed in the absence of SPARC.

SPARC (Secreted Protein Acidic and Rich in Cysteine) is a multifunctional glycoprotein belonging to a group of matrix-associated factors that mediate cell-extracellular matrix interactions but have no structural roles. In the present study we investigated the contribution of SPARC to factors that influence the development of skin tumors in response to UV irradiation. A hairless SPARC-null mouse was developed and compared to control SKH1 hairless mice in terms of skin tumor induction and extracellular matrix changes occurring in response to UV-irradiation. Following 23 weeks of exposure to UVB totaling 14.5 J per cm(2), tumor development in the wild-type mice was severe, with an average of over 20 tumors per mouse, many of which were squamous cell carcinomas. Conversely, the SPARC-null mice were strikingly tumor-resistant, developing no squamous cell carcinomas and averaging less than one small papilloma per mouse. SPARC was undetectable immunohistochemically in skin from the non-irradiated control group yet was present in relatively high quantities in the basal and superficial areas of the tumor mass. The SPARC-null mice also exhibited a limited contact hypersensitivity response and were refractory to UV induced immune suppression. In conclusion, SPARC appears to have a crucial role in mediating tumor formation in response to UV irradiation.

Aspectos dermatológicos da acromegalia

Acromegalia é rara síndrome endócrina que se caracteriza pela hiperplasia mesenquimal. Em geral sua manifestação é insidiosa ao extremo, e, como cursa precocemente com alterações cutâneas, o dermatologista pode ser o primeiro profissional médico a ser procurado pelo paciente. Os autores fazem uma descrição dos achados clínicos e dermatológicos dessa afecção.

Early Cutaneous Alterations in Experimental Sepsis by Pseudomonas aeruginosa

Background: To evaluate whether histopathologic findings of skin in sepsis by Pseudomonas aeruginosa correlate with the clinical course. Methods: Histological alterations after bacterial challenge by one susceptible (A) and two multidrug-resistant isolates (B and C) of P. aeruginosa were studied in 18 rabbits. Sepsis was induced by the intravenous infusion of 1 × 10⁸ CFU by a catheter in the right jugular vein; blood was sampled for the estimation of tumor necrosis factor α (TNF-α) and malondialdehyde (MDA). Skin biopsies were collected along with a subcutaneous fat specimen for culture. Results: The mean survival was 0.85, 1.75 and 11.00 days after challenge by isolates A, B and C, respectively. The main histologic findings of skin were: inflammation and swelling of the dermis; thickening of the endothelium and infiltration of vessel wall and lumen by polymorphonuclear leukocytes; extravasation of red blood cells, and necrobiotic changes of the hair follicles. Serum TNF-α was elevated in animals challenged by isolate A compared to challenge by isolates B and C. Concentrations of MDA were similar for all isolates. Mean log₁₀ of viable cells isolated from subcutaneous fat were 5.74, 2.74 and 1.40 after challenge by isolates A, B and C, respectively. Conclusions: Prolongation of survival was accompanied by lower serum TNF-α, decreased viable cells from subcutaneous fat and intensified inflammatory response in the dermis and subcutaneous tissue. These findings might be of importance for immunomodulatory intervention.

Impaired pressure-induced vasodilation at the foot in young adults with type 1 diabetes.

Vascular and neurological mechanisms are both likely to be involved in foot ulcer. We recently reported a pressure-induced vasodilation (PIV), relying on unmyelinated afferent excitation. We previously found that cutaneous blood flow in response to locally applied pressure might be impaired in diabetic patients because of the combined effects of low cutaneous temperature and alterations in microcirculatory function. Therefore, we aimed to analyze whether, at a relatively high cutaneous temperature, PIV is present in type 1 diabetes and to assess endothelial-dependent vasodilation and endothelium-independent vasodilation. We measured cutaneous blood flow using laser Doppler flowmetry on the head of the first metatarsus in response to applied pressure at 5.0 mmHg/min in warm conditions (29.5 +/- 0.2 degrees C). Responses to iontophoresis of acetylcholine (endothelium dependent) and sodium nitroprusside (endothelium independent) were measured using laser Doppler flowmetry in the forearm. The data indicate that PIV exists at the foot level in normal subjects, whereas it was not found in diabetic patients. In diabetic patients, the nonendothelial-mediated response to sodium nitroprusside was preserved, whereas the endothelial-mediated response to acetylcholine was impaired. These findings might be relevant to the high prevalence of foot ulcer that occurs in diabetic patients.

Isolated flat capillary midline lumbosacral hemangiomas as indicators of occult spinal dysraphism.

Historically, cutaneous stigmata representative of occult spinal dysraphism (OSD) have included lumbar hemangiomas. Frequently, this skin change is found in conjunction with other cutaneous alterations such as dermal sinus tracts and subcutaneous lipomas. Debate has recently surrounded the question of whether these skin changes in isolation might indicate underlying spinal disease. The authors reviewed their experience in their most recent 120 cases in which OSD was diagnosed. The authors retrospectively reviewed records obtained in 120 patients with OSD. They found that many of the patients reviewed harbored only a flat capillary hemangioma as an indicator of OSD. In 21 patients (17.5%) with only midline lumbosacral flat capillary hemangiomas, underlying OSD was present. No single variety of OSD had a higher incidence of association with this single cutaneous stigma. Based on their experience, the authors recommend magnetic resonance (MR) imaging evaluation in cases involving this skin lesion in isolation to discern the potential for surgically significant spinal cord anomalies. Prospective studies are now needed to examine MR images obtained in all children with this lesion in the midline lumbosacral spine and assess for OSD.

A reappraisal of the histologic findings of pigmented pretibial patches of diabetes mellitus.

Pigmented pretibial patches (PPPs) are the most common cutaneous alterations in diabetes mellitus, found in up to 50% of diabetic patients. They classically present as flat-topped, dull-red papules on the pretibial areas, later becoming hyperpigmented and atrophic. Little is known regarding the pathogenesis of these lesions, and the histopathologic findings have been regarded as non-specific. We investigated the clinical and pathologic attributes of a series of 12 diabetic patients with PPP in an effort to discern any specific histologic attributes compared to normal skin removed from diabetic patients with cutaneous carcinoma. All cases of PPP showed hyaline microangiopathy, all patients showed extravasated erythrocytes and/or hemosiderin deposits, and 10 patients showed an appreciable number of perivascular plasma cells. The average number of plasma cells per vascular plexus was 2.2. Control specimens removed from five diabetic patients showed hyaline microangiopathy, and three showed extravasated erythrocytes and hemosiderin. One patient showed a single vascular plexus with two plasma cells, p = 0.01. The presence of increased dermal perivascular plasma cells in the appropriate clinical context might be an important and under-recognized clue for PPP. The pathogenic significance of this finding is unknown.

Alterações dermatológicas em crianças com Aids e sua relação com categorias clínico-imunológicas e carga viral

FUNDAMENTOS: Desde o início da epidemia da Aids as dermatoses têm sido freqüentemente descritas em pacientes com essa doença, com relatos de casos atípicos e estudos de séries de pacientes adultos; no entanto, há poucas publicações sobre alterações cutâneas em pacientes pediátricos com Aids. OBJETIVOS: Estudo prospectivo para avaliar a presença de dermatoses em 40 pacientes pediátricos com Aids. MÉTODOS: Quarenta pacientes, com idade inferior a 13 anos e portadores de Aids, foram estudados por um período de seis meses para avaliação de: número de alterações dermatológicas; suas características clínicas; distribuição conforme as categorias clínico-imunológicas e o valor da carga viral. RESULTADOS: A prevalência de dermatoses foi de 82,4%, na primeira consulta, e, no acompanhamento longitudinal, 92,5% dos pacientes tiveram alterações dermatológicas, com proporção de cinco diagnósticos por doente. As crianças com classificação clínico-imunológica grave e carga viral acima de 100.000 cópias/ml apresentaram maior número de alterações dermatológicas quando comparadas àquelas das categorias clínico-imunológicas leves. A proporção de diagnósticos por paciente na categoria clínica C foi de 6,8 e na A de 3,6; na categoria imunológica grave, de sete, e na leve de 3,7; e na carga viral > 100.000 de 7,3, e na < 100.000 de 4,2 (todos com significância estatística). CONCLUSÃO: As dermatoses foram freqüentes nas crianças com Aids e ocorreram em maior número nos pacientes pertencentes às categorias graves. A elevada freqüência de alterações da pele nos pacientes pediátricos com a doença indica ser imprescindível sua avaliação dermatológica minuciosa e freqüente.

Histopathological and immunohistochemical assessment of acquired ichthyosis in patients with human T-cell lymphotropic virus type I-associated myelopathy.

Patients with human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy frequently display cutaneous alterations such as acquired ichthyosis. Elucidation of the pattern of acquired ichthyosis in HTLV-I-associated myelopathy. Skin fragments from 10 patients with HTLV-I-associated myelopathy presenting with acquired ichthyosis were assessed by histopathological and immunohistochemical tests. We used anticytokeratin antibodies related to normal keratinization (K1/K10), and others related to cutaneous conditions such as activation, migration and hyperproliferation of keratinocytes (K6/K16), and involucrin, a precursor protein in the formation of the protein envelope in keratinocytes. For quantification of the proliferating basal and parabasal cells the anti-Ki-67 antibody was employed. On light microscopy, all skin specimens displayed orthokeratotic hyperkeratosis and hypogranulosis. Three of them presented focal parakeratosis. A slight to moderate perivascular infiltrate of mononuclear lymphocytes was observed in seven cases, three of which showed discrete spongiosis with epidermotropism of lymphocytes. All fragments displayed coexpression of K1, K10 and K16 in the suprabasal layers. Expression of involucrin was also observed in all cases, in the upper spinous and granular layers. Focal expression of K6 was observed in three cases, under a parakeratotic area. The mean number of Ki-67+ basal and parabasal cells was 3.5 cells per mm, similar to that in control skin. In acquired ichthyosis related to HTLV-I-associated myelopathy, histopathology revealed orthokeratotic hyperkeratosis and a perivascular inflammatory infiltrate of mononuclear lymphocytes, with areas of parakeratosis and foci of epidermotropism in rare cases. The expression profiles of K1, K10 and involucrin were similar to those in normal skin. The diffuse coexpression of K16 with K1 and K10 throughout the analysed epidermis, as well as the occurrence of restricted areas of parakeratosis expressing K6, indicate the presence of keratinocyte activation with induction of the alternative keratinization pathway, probably dependent on the cytokines liberated by the mononuclear cells of the dermal inflammatory infiltrate infected with HTLV-I. The absence of acanthosis and of increased cellular kinetics, as shown by the low rate of Ki-67 antigen expression, allow the inference that the pattern of acquired ichthyosis related to HTLV-I-associated myelopathy may be retentional. The observation of foci of parakeratosis expressing K6 in three specimens suggests that, at least in certain areas and in some cases, interference with epidermal differentiation and maturation occurs.

Eosinophilic Meningitis.

Eosinophilic meningitis (EM) is a distinct clinical entity that may have infectious and noninfectious causes. Worldwide, infection with the helminthic parasite, Angiostrongylus cantonensis, is the most common infectious etiology. Historically, this infection has been acquired through ingestion of competent intermediate and paratenic (carrier) hosts or contaminated food in Southeast Asia and the Pacific Islands. A recent outbreak of A. cantonensis-associated EM among US travelers to Jamaica and subsequent parasitologic surveys of local snails and rats confirm earlier case reports and engender a wider appreciation of the Caribbean islands as a new region for endemic A. cantonensis infections. Clinically, eosinophilia is not always present in the cerebrospinal fluid or in the peripheral blood during the initial manifestions of A. cantonensis-associated EM, which include headache and cutaneous sensory alterations. Effective management of patients involves careful attention to the control of intracranial pressure. Steroid therapy without specific anthelmintic treatment is safe and effective in control of headache of adult patients with A. cantonensis-associated EM.