Evaluation of Demodex mite viability using motility and scattered light intensity.

Demodex mites have been suggested to have a role in various cutaneous and ocular disorders pathogenesis, such as rosacea or blepharitis. Evaluation of potential treatments with anti-Demodex effects is difficult because the viability of living mites needs to be evaluated during their exposure to the agent being tested. Mite viability is currently based solely on their observed movement. However, this method of assessing viability has significant limitations as mites may be resting, immobile or paralysed at any given observation point giving the observer a false impression of the organism's death. To overcome this limitation we evaluated a new quantitative method of evaluating the viability of Demodex mites by using scattered light intensity (SLI). We demonstrated that when combined with observation of mite motility, SLI provided increased accuracy of the evaluation of viability of mites being studied. This new viability assay will help address the technical challenges of mite viability experiments. Accurate evaluation of mite viability will enhance mite biology research and allow for more accurate in vitro toxicity assays of proposed anti-mite agents.

Demodex mites modulate sebocyte immune reaction: possible role in the pathogenesis of rosacea.

BACKGROUND: Rosacea is a common facial skin disorder mainly affecting middle-aged adults. Its aetiology is unknown and pathogenesis uncertain. Activation of the host innate immune response has been identified as an important factor. The Demodex mite population in the skin of rosacea patients is significantly higher than in patients with normal skin, suggesting that they may be of aetiological importance in this disorder. OBJECTIVES: To determine the potential of Demodex mites to interact with the host immune system. METHODS: Live Demodex mites were extracted from normal facial skin of control subjects and used in cell stimulation experiments with the immortalized SZ95 sebocyte line. Time- and mite-dose-dependent experiments were performed. Direct effects of Demodex and effects of the medium in which Demodex had been cultured were evaluated on the Toll-like receptor (TLR) signalling pathway on both a gene and protein expression level. RESULTS: Mites modulated TLR signalling events on both mRNA and protein levels in SZ95 sebocytes. An initial trend towards downmodulation of genes in this pathway was observed. A subsequent switch to positive gene upregulation was recorded after 48 h of coculture. Demodex secreted bioactive molecules that affected TLR2 receptor expression by sebocytes. High numbers of Demodex induced proinflammatory cytokine secretion, whereas lower numbers did not. CONCLUSIONS: Demodex mites have the capacity to modulate the TLR signalling pathway of an immortalized human sebocyte line. Mites have the capacity to secrete bioactive molecules that affect the immune reactivity of sebocytes. Increasing mite numbers influenced interleukin-8 secretion by these cells.

Study of Demodex mites: Challenges and Solutions.

Demodex mites are the largest and most complex organisms of the skin microflora. How they interact with the innate and adaptive immune systems is unknown. Their potential to have a pathogenic role in the causation of human skin disorders causes continued speculation. With growing interest in the microflora of human skin and its relevance to cutaneous health, the role of Demodex mites needs to be better understood. The main challenges facing scientists investigating the role of these organisms and possible solutions are reviewed under the following headings: (1) Determining the mite population in skin, (2) Transporting, extracting and imaging live mites, (3) Maintaining mites viable ex vivo and (4) Establishing methods to determine the immune response to Demodex mites and their internal contents.

Epidermal hydration levels in patients with rosacea improve after minocycline therapy.

BACKGROUND: Patients with rosacea frequently report increased skin sensitivity, with features suggestive of an abnormal stratum corneum (SC) permeability barrier. Sebum, pH and hydration levels influence epidermal homeostasis. The correlation of changes in these parameters with clinically effective treatment has not been previously analysed. OBJECTIVES: To analyse sebum, pH and epidermal hydration levels of patients with papulopustular rosacea (PPR) before and after treatment with systemic minocycline. METHODS: We analysed sebum casual levels, pH and hydration along with erythema levels (as a marker of disease activity and response to treatment) on seven designated facial sites of 35 patients with active PPR and compared the results with values on the same sites of 34 control subjects with normal facial skin. To determine the effect of minocycline on these parameters, we re-examined the patients with PPR at the same sites after a 6-week course of treatment. RESULTS: Patients with untreated PPR had significantly increased erythema indices, normal sebum casual levels, a more alkaline centrofacial region and reduced epidermal hydration levels compared with controls. Treatment with minocycline resulted in reduced erythema and increased hydration levels, with the most marked changes evident in the cheeks (13·3% reduction in erythema indices, P < 0·001; 12·4% increase in hydration levels, P = 0·012). There was no change in skin pH or sebum casual levels following treatment. CONCLUSION: Patients with PPR have increased erythema indices, normal sebum casual levels, a more alkaline centrofacial region and reduced epidermal hydration levels compared with control subjects. Treatment with systemic minocycline reduces erythema and increases hydration, in the absence of any change in skin pH or sebum casual levels.

The fatty acid profile of the skin surface lipid layer in papulopustular rosacea.

BACKGROUND: Patients with papulopustular rosacea (PPR) frequently complain of dry, sensitive skin. We have previously demonstrated that patients with PPR have reduced skin surface hydration levels in the presence of normal sebum casual levels, suggesting that it may be the quality and not the quantity of sebum that plays a role in PPR. OBJECTIVES: To compare the sebaceous fatty acid composition of patients with PPR to that of controls with normal facial skin. METHODS: The sebaceous fatty acid composition of 25 patients with PPR and 24 age- and sex-matched controls was analysed by gas chromatography - mass spectrometry. Results Myristic acid (C14:0) was present in greater concentrations in PPR sebum, while the long chain saturated fatty acids arachidic acid (C20:0), behenic acid (C22:0), tricosanoic acid (C23:0) and lignoceric acid (C24:0) as well as the monounsaturated fatty acid cis-11-eicosanoic acid (C20:1) were present in the sebum of patients with PPR in lesser concentrations as compared with controls. CONCLUSIONS: There is increasing evidence that sebaceous fatty acids play a role in the maintenance of skin barrier integrity. We have shown for the first time that patients with PPR have an abnormal sebaceous fatty acid composition, with reduced levels of long chain saturated fatty acids. These new findings may have therapeutic implications for the development of sebum-modifying nonantibiotic treatments for patients with PPR.

Calciphylaxis in a patient with normal renal function: response to treatment with sodium thiosulfate.

Calciphylaxis is a rare, life-threatening cause of skin necrosis. The condition is primarily reported in patients with end-stage renal disease, and is associated with significant morbidity and mortality. Treatment has mainly been empirical. We report a case of calciphylaxis in a patient with normal renal function and hypoparathyroidism, who responded to treatment with sodium thiosulfate. To our knowledge, this is the first reported case of the use of sodium thiosulfate to treat calciphylaxis in a patient with normal renal function.

The pathophysiology of rosacea.

Rosacea is thought to be a common skin disorder in the general population, presenting with many different clinical features and unknown causes. Theories of pathogenesis have been extrapolated from clinical observation of factors, leading to a definition of the etiology of rosacea which was very limited until recently. A recent upsurge in translational research in rosacea has significantly advanced the insight into this disease. In this review the authors discuss the pathogenesis of this disease, which could be determined by the following factors: 1) exposure to UV radiation; 2) reactive oxygen species (including superoxide and hydroxyl radicals, hydrogen peroxide and singlet oxygen); 3) vascular hyperreactivity; 4) neuropeptides; 5) exacerbation of innate immune response; 6) microbes, in particular H. pylori and environmental aggressors, such as Demodex mite. Even if the recent investigations have significantly improved the understanding of its pathogenesis, the authors conclude that the histopathology of rosacea remains to be clarified according to subtype and age of development of individual lesions.

Pyoderma gangrenosum manifesting as a cavitating lung lesion.

We present a case of pyoderma gangrenosum (PG) mimicking a lung carcinoma. A 52-year-old woman presented with an unremitting cough. Computed tomography revealed a cavitating lung lesion. Bronchoscopy and biopsy were interpreted as squamous cell carcinoma. Following a staging mediastinoscopy, a sleeve lobectomy and chest-wall resection was performed. The pulmonary histopathological features suggested Wegener's granulomatosis; no malignancy was found. Three months postoperatively, wound breakdown led to dermatological review. A clinical diagnosis of cutaneous PG was made on the basis of the classic appearance of the surgical wounds and an ulcer on the upper back that had been present before surgery. The patient has been consistently negative for cytoplasmic-staining antineutrophil cytoplasmic antibodies, which supports the diagnosis of PG with cutaneous and pulmonary involvement. Lung manifestations of PG are rare. PG is amenable to systemic therapy. Pulmonary PG is a rare but important differential diagnosis that is not familiar to many physicians and surgeons in this type of presentation.

Cutaneous sarcoidal reaction in a patient with pulmonary tuberculosis.

Sarcoidosis is a systemic disorder characterized by non-caseating epithelioid granulomas that may affect any organ system. The etiology of sarcoidosis is unknown, but several immune aberrations are thought to play a role in its pathogenesis. The possible role of mycobacterial infection in the pathogenesis of sarcoidosis has been suggested. In recent studies mycobacterial DNA was detected in lung tissues and bronchial lavage fluid of 30% to 50% of patients with sarcoidosis. We report a patient with pulmonary tuberculosis treated successfully three years earlier who developed cutaneous sarcoidosis with negative polymerase chain reaction (PCR) assay for mycobacterial DNA of the skin lesion.

Treatment of parapsoriasis and mycosis fungoides: the role of psoralen and long-wave ultraviolet light A (PUVA).

Psoralen and long-wave ultraviolet light A (PUVA) was used to treat 12 patients with parapsoriasis and 19 patients with mycosis fungoides. Excellent results were obtained in all 12 patients with parapsoriasis: 8 patients had complete clearing, 3 had more than 80% improvement, and 1 had considerable improvement. The response to PUVA in patients with mycosis fungoides varied according to the stage of the disease. Of 10 patients with early disease (stage I or II), 7 had complete clearing and the 3 others had more than 80% improvement. The nine patients with more advanced disease generally did not respond well to PUVA, with the exception of one patient with stage IV disease and one with stage V disease. PUVA may be the treatment of choice for parapsoriasis and is highly effective in the early stages of mycosis fungoides.

The anticentromere antibody: disease specificity and clinical significance.

Serum samples from 539 subjects were screened for the presence of the anticentromere antibody on a human laryngeal carcinoma (HEp-2) cell line (Antibodies, Inc.). The antibody was present in 61 patients (11%), most of whom had features of limited scleroderma or the CREST syndrome (calcinosis cutis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia), either independently or in association with primary biliary cirrhosis. The antibody was rarely found in patients with rapidly advancing or diffuse scleroderma. The anticentromere antibody is therefore a useful prognostic indicator in patients with early scleroderma, as it may help to predict what pattern of scleroderma will evolve. Screening for this antibody should be conducted in all patients with Raynaud's phenomenon, primary biliary cirrhosis, and scleroderma. Other previous studies have indicated a similar disease specificity and prognostic importance of this antibody.

Pyoderma gangrenosum in childhood.

A review of our records disclosed eight children with pyoderma gangrenosum. All had associated inflammatory bowel disease, and four had arthritis. In three patients the bowel disease was severe and required resection of portions of the affected bowel. The cutaneous lesions had a chronic course (average duration, 2 1/2 years), and systemic therapy was required in seven cases. Previously reported cases of pyoderma gangrenosum in children are reviewed, and the management of this skin disorder in childhood is discussed.

Metastatic prostate carcinoma manifesting as penile nodules.

In three patients with prostate carcinoma, metastasis was manifested as nodular lesions about the corona and glans penis. One patient had priapism in addition. The patients had no other cutaneous metastatic lesions. Two of the patients died within two years of the appearance of the penile nodules, but the lesions in the third patient, followed up for one year to date, responded to intravenously administered mitomycin.

Pyoderma gangrenosum and monoclonal gammopathy.

The records of eight patients with pyoderma gangrenosum and monoclonal gammopathy showed that all patients except one had an IgA paraproteinemia. To date, seven patients have had a benign course and multiple myeloma has developed in one. In seven patients, the onset of the pyoderma gangrenosum preceded the detection of the monoclonal gammopathy. The monoclonal gammopathy did not seem to influence the morphologic findings, course, or therapy of the pyoderma gangrenosum. In the one patient with myeloma, treatment of the myeloma caused accelerated healing of the skin lesions.

A risk/benefit analysis of spinal manipulation therapy for relief of lumbar or cervical pain.

Approximately 12 million Americans undergo spinal manipulation therapy (SMT) every year. Renewed interest in this method requires an analysis of its reported risks and possible benefits. This review describes two patients with spinal cord injuries associated with SMT and establishes the risk/benefit ratios for patients with lumbar or cervical pain. The first case is a man who underwent SMT for recurrent sciatica 4 years after chemonucleolysis. During therapy, he developed bilateral sciatica with urinary hesitancy. After self-referral, myelography demonstrated a total block; he underwent urgent discectomy with an excellent result 3 months after surgery. The second patient with an indwelling Broviac catheter and a history of lumbar osteomyelitis underwent SMT for neck pain. Therapy continued for 3 weeks despite the development of severe quadriparesis. After self-referral, he underwent an urgent anterior cervical decompression and removal of necrotic bone and an epidural abscess with partial neurological recovery. An analysis of these cases and 138 cases reported in the literature demonstrates six risk factors associated with complications of SMT. These include misdiagnosis, failure to recognize the onset or progression of neurological signs or symptoms, improper technique, SMT performed in the presence of a coagulation disorder or herniated nucleus pulposus, and manipulation of the cervical spine. Clinical trials of SMT have been summarized in several recent articles.(ABSTRACT TRUNCATED AT 250 WORDS)