Which factors influence Demodex mite density in standardized superficial skin biopsy in patients with rosacea? A prospective cross-sectional analysis.

Rosacea is a chronic cutaneous disease that manifests with facial erythema, telangiectasia, papules and pustules on the central face. Although the pathogenesis is not well established, rosacea appears to have a close relationship with Demodex mites. The aim of the study was to elucidate the factors influencing Demodex mite density by standardized superficial skin biopsy (SSSB) in patients with rosacea. This prospective, cross-sectional study included 200 patients with rosacea. Clinical characteristics of the patients were recorded and SSSB was used to measure Demodex density (Dd). If Dd was < 5 D/cm2 in the first SSSB, SSSB was repeated 4 more times to avoid false negative results. Of 200 patients, 152 (76%) were females and 48 (24%) males with a mean age of 43.47 ± 11.87 years. Ninety-nine patients (49.5%) had erythematotelangiectatic (ETR) and 101 patients (50.5%) had papulopustular (PPR) subtype of rosacea. Among 200 patients, the ratio of cumulative positive results of the consecutive SSSBs were as follows: 1st SSSB = 125 (62.5%), 2nd SSSB = 155 (77.5%), 3rd SSSB = 170 (85%), 4th SSSB = 173 (86.5%) and 5th SSSB = 174 (87%). The ratio of detecting Demodex infestation in the first SSSB was significantly lower in patients with PPR (55/101, 54.5%) than in patients with ETR (70/99, 70.7%). Median total Demodex mite density and D. folliculorum density were significantly higher in the ETR group than in the PPR group. There was a statistically significant relationship between density of Demodex tails in dermoscopy and positive/negative results of Demodex infestation in SSSB. As a conclusion, Demodex mite density by SSSB was influenced by various factors such as subtypes of rosacea, types of Demodex species, and dermoscopic findings.

Evidence for the Clinical Association between Demodex and Rosacea: A Review.

BACKGROUND: Rosacea is a chronic inflammatory dermatological condition in humans, and its pathogenesis remains unclear. However, the development of rosacea is suspected to be related to Demodex, a microscopic commensal organism that resides in or near hair follicles and sebaceous glands. Although Demodex is known to be a host-specific, obligate commensal organism, it is currently difficult to be cultured in vitro to parasitize and infect other animal hosts. Therefore, direct evidence for a pathogenic role of Demodex in rosacea is currently lacking. SUMMARY: As circumstantial evidence, non-invasive skin-detecting techniques have shown abnormally elevated numbers of Demodex in rosacea patients. Increased cytokine levels such as IL-10, IL-8, and IL-12p70 have been observed in human sebocytes following the Demodex challenge, and acaricides have been found to be effective in rosacea therapy, all point to a close relationship between Demodex and rosacea. Based on these findings, we conducted a comprehensive literature review to summarize the current state of knowledge, research insights, and clinical treatment recommendations for Demodex-associated rosacea, with the ultimate goal of improving patient outcomes.

Investigation of the Prevalence of Demodex spp. in Dermatological Diseases

Objective: An increase in the counts of the Demodex mites that exist in the microbiota of healthy individuals may lead to some dermatological diseases. This study aimed to investigate the prevalence of Demodex spp. among patients diagnosed with acne vulgaris, rosacea, perioral dermatitis, seborrheic dermatitis, eczema, and pityriasis folliculorum and the relationship between the demographic and clinical data of such patients and Demodex. Methods: This study included 144 patients (70 with acne vulgaris, 6 with pityriasis folliculorum, 15 with seborrheic dermatitis, 39 with rosacea, 8 with eczema, and 6 with perioral dermatitis) and 73 healthy subjects. We evaluated Demodex positivity using the standard superficial skin biopsy method in all groups. The presence of more than five Demodex mites per square centimeter was considered positive at the diagnosis. Results: Of the 144 patients included in the study, 107 (74.3%) were female, and 37 (25.7%) were male, while 40 (54.8%) of the 73 healthy subjects were female, and 33 (45.2%) were male. Twenty-one patients (14.5%) and five of the healthy subjects (6.8%) tested positive for Demodex. We found that Demodex positivity rates in the rosacea and acne vulgaris groups were higher than in the control group. However, this level was not statistically significant (p>0.05). We found the highest positivity rate among the patient groups in the pityriasis folliculorum (4/6, 66.7%), rosacea (8/39, 20.5%), and perioral dermatitis (1/6, 16.7%) groups. Lastly, we found no statistically significant relationship between the demographic and clinical characteristics of the groups and Demodex positivity (p>0.05). Conclusion: The present study is the only study that investigated Demodex positivity in six different dermatological diseases. Based on the results, we believe that investigating Demodex spp. positivity in dermatological diseases such as acne vulgaris, rosacea, and pityriasis folliculorum would be beneficial for early diagnosis and treatment.

Dermoscopy of papulopustular rosacea and comparison of dermoscopic features in patients with or without concomitant Demodex folliculorum.

BACKGROUND: The dermoscopic findings of papulopustular rosacea include tiny papules and pustules, follicular plugs and follicular dilatation. Demodex tails and Demodex follicular openings are dermoscopic indicators that are mainly found in primary demodicosis and, less frequently, in rosacea. AIM: To describe the dermoscopic features of papulopustular rosacea and to investigate the differential dermoscopic features between patients with and without concomitant Demodex infestation. METHODS: We conducted a prospective study of patients with almost-clear, mild or moderate papulopustular rosacea. For each patient, dermoscopic images were taken and a standardized skin surface biopsy was performed. RESULTS: In this group of 60 patients, the most frequent dermoscopic findings were yellow dots, vascular polygons and follicular scales. Patients with moderate rosacea had more Demodex follicular openings compared with patients with mild rosacea (P = 0.02), while patients with mild rosacea had a higher frequency of follicular scales than did patients with almost-clear rosacea (P = 0.01). Patients with moderate rosacea had higher rates of Demodex follicular openings (P = 0.02), follicular scales (P < 0.001), follicular annular pigmentation (P = 0.001) and follicular pustules (P < 0.001) compared with patients with almost-clear rosacea. No significant dermoscopic differences were observed between patients with and without concomitant Demodex infestation. CONCLUSIONS: Papulopustular rosacea has specific dermoscopic findings. In our opinion, dermoscopy is not sufficient by itself for the diagnosis of Demodex proliferation in rosacea.

Case Report: A New Gain-of-Function Mutation of STAT1 Identified in a Patient With Chronic Mucocutaneous Candidiasis and Rosacea-Like Demodicosis: An Emerging Association.

Purpose: Heterozygous missense STAT1 mutations leading to a gain of function (GOF) are the most frequent genetic cause of chronic mucocutaneous candidiasis (CMC). We describe the case of a patient presenting a new GOF mutation of STAT1 with the clinical symptoms of CMC, recurrent pneumonia, and persistent central erythema with papulopustules with ocular involvement related to rosacea-like demodicosis. Methods: Genetic analysis via targeted next-generation sequencing (NGS; NGS panel DIPAI v.1) exploring the 98 genes most frequently involved in primary immunodeficiencies, including STAT1, was performed to identify an underlying genetic defect. Results: NGS identified a novel variant of STAT1, c.884C>A (exon 10), p.T295Y, not previously described. This variant was found to be gain of function using an in vitro luciferase reporter assay. Rosacea-like demodicosis was confirmed by substantial Demodex proliferation observed via the microscopic examination of a cutaneous sample. A review of literature retrieved 20 other cases of STAT1 GOF mutations associated with early-onset rosacea-like demodicosis, most with ocular involvement. Conclusion: We describe a new STAT1 GOF mutation associated with a phenotype of CMC and rosacea-like demodicosis. Rosacea-like demodicosis appears as a novel and important clinical phenotype among patients with STAT1 GOF mutation.

Demodex folliculorum infestations in common facial dermatoses: acne vulgaris, rosacea, seborrheic dermatitis.

BACKGROUND: Demodex mites are found on the skin of many healthy individuals. Demodex mites in high densities are considered to play a pathogenic role. OBJECTIVE: To investigate the association between Demodex infestation and the three most common facial dermatoses: acne vulgaris, rosacea and seborrheic dermatitis. METHODS: This prospective, observational case-control study included 127 patients (43 with acne vulgaris, 43 with rosacea and 41 with seborrheic dermatitis) and 77 healthy controls. The presence of demodicosis was evaluated by standardized skin surface biopsy in both the patient and control groups. RESULTS: In terms of gender and age, no significant difference was found between the patients and controls (p>0.05). Demodex infestation rates were significantly higher in patients than in controls (p=0.001). Demodex infestation rates were significantly higher in the rosacea group than acne vulgaris and seborrheic dermatitis groups and controls (p=0.001; p=0.024; p=0.001, respectively). Demodex infestation was found to be significantly higher in the acne vulgaris and seborrheic dermatitis groups than in controls (p=0.001 and p=0.001, respectively). No difference was observed between the acne vulgaris and seborrheic dermatitis groups in terms of demodicosis (p=0.294). STUDY LIMITATIONS: Small sample size is a limitation of the study. The lack of an objective scoring system in the diagnosis of Demodex infestation is another limitation. CONCLUSION: The findings of the present study emphasize that acne vulgaris, rosacea and seborrheic dermatitis are significantly associated with Demodex infestation. Standardized skin surface biopsy is a practical tool in the determination of Demodex infestation.

Case for diagnosis. Erythematous and pruritic papules on forearms

Abstract Gamasoidosis is a poorly known and underdiagnosed mite infestation. It is characterized by the presence of erythematous and flattened papules that are quite pruritic, and can affect any region of the body, with preference for areas of folds. This article reports a case of the disease caused by mites of the species Dermanyssus gallinae. Increasingly, the agents that cause this disease are found in urban environments, increasing the incidence of people affected by the disease. This dermatosis has a self-limiting clinical picture and the treatment is done with the use of topical corticosteroids and oral antihistamines.

Demodex folliculorum infestations in common facial dermatoses: acne vulgaris, rosacea, seborrheic dermatitis

Abstract Background: Demodex mites are found on the skin of many healthy individuals. Demodex mites in high densities are considered to play a pathogenic role. Objective: To investigate the association between Demodex infestation and the three most common facial dermatoses: acne vulgaris, rosacea and seborrheic dermatitis. Methods: This prospective, observational case-control study included 127 patients (43 with acne vulgaris, 43 with rosacea and 41 with seborrheic dermatitis) and 77 healthy controls. The presence of demodicosis was evaluated by standardized skin surface biopsy in both the patient and control groups. Results: In terms of gender and age, no significant difference was found between the patients and controls (p > 0.05). Demodex infestation rates were significantly higher in patients than in controls (p = 0.001). Demodex infestation rates were significantly higher in the rosacea group than acne vulgaris and seborrheic dermatitis groups and controls (p = 0.001; p = 0.024; p = 0.001, respectively). Demodex infestation was found to be significantly higher in the acne vulgaris and seborrheic dermatitis groups than in controls (p = 0.001 and p = 0.001, respectively). No difference was observed between the acne vulgaris and seborrheic dermatitis groups in terms of demodicosis (p = 0.294). Study limitations: Small sample size is a limitation of the study. The lack of an objective scoring system in the diagnosis of Demodex infestation is another limitation. Conclusion: The findings of the present study emphasize that acne vulgaris, rosacea and seborrheic dermatitis are significantly associated with Demodex infestation. Standardized skin surface biopsy is a practical tool in the determination of Demodex infestation.

Demodicosis in a captive African straw-coloured fruit bat (Eidolon helvum).

Demodicosis is most frequently observed in the domestic dog (Canis familiaris), but it has rarely been reported in bats (Chiroptera). The overpopulation of Demodex spp. that causes dermatological changes is generally associated with a compromised immune system. We describe the gross and histological features of generalized demodicosis in an adult female African straw-coloured fruit bat (Eidolon helvum) drawn from a captive research colony. The histology of the lesions revealed comedones and follicular infundubular cysts harbouring numerous Demodex spp. mites, eliciting a minimal inflammatory response in the adjacent dermis. The histological examination of a full set of tissues did not reveal clear evidence of immunosuppression, although a clinical history of recent abortion and possible stressors due to captivity could be considered risk factors for the demodicosis. Attempts to determine the Demodex species using PCR on DNA extracted from the formalin fixed paraffin embedded tissue failed. This is the first clinical and histological description of demodicosis in Eidolon helvum.

An Unusual Presentation of Pyemotes ventricosus Dermatitis Presenting With Umbilicated Papules Mimicking Poxvirus Infection.

Pyemotes ventricosus mites are an uncommon cause of pruritic dermatitis seen most commonly in occupational exposure, prominently found in professionals such as farmers, landscapers, and factory workers who work with grains, wheat, dried beans, or grasses. The clinical description of the rash has typically been described as papular, erythematous, with a central vesicular lesion. We describe a case of Pyemotes dermatitis with an atypical clinical presentation. A 30-year-old man presented with pruritic, umbilicated papules, which involved his right lateral trunk and upper thigh leading to the submitted clinical impression of molloscum contagiosum. A biopsy of the skin was taken, and fragments of arthropod consistent with P. ventricosus were identified within umbilicated indentations of skin. The patient subsequently admitted to the onset of the rash immediately after carrying bales of straw while supporting each bale with his right side. The possibility of Pyemotes dermatitis mimicking a poxvirus-like eruption should be considered when encountering an unusual umbilicated papular eruption in the appropriate patient with occupational exposure.

Rosacea and Demodicosis: Little-known Diagnostic Signs and Symptoms.

Papulopustular rosacea and demodicosis are characterized by non-specific symptoms, which can make clinical diagnosis difficult. This retrospective study of 844 patients assessed the diagnostic importance of clinical signs and symptoms that are poorly recognized as being associated with these conditions. In addition to well-known signs (vascular signs (present in 80% of patients), papules (39%), pustules (22%) and ocular involvement (21%)), other signs and symptoms (discreet follicular scales (93%), scalp symptoms (pruritus, dandruff or folliculitis; 38%) and pruritus (15%)) may also suggest a diagnosis not only of demodicosis, but also of papulopustular rosacea. Facial Demodex densities (measured by 2 consecutive standardized skin biopsies) were higher when ocular or scalp involvement was present, suggesting more advanced disease, but further investigations are needed to confirm this hypothesis. Recognition of these clinical signs and symptoms should encourage dermatologists to perform a Demodex density test, thus enabling appropriate diagnosis to be made.

Hidradenitis Suppurativa, Metabolic Syndrome, and Demodex spp. Infestation.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. This type of dermatosis with underlying chronic inflammation significantly affects the quality of life and may be accompanied by many comorbidities. In this case, Demodex spp. was associated with treatment-resistant and persistent course of skin diseases. A 46-year-old female patient applied to our clinic with complaints of lesions on the body and hip. Her dermatological examination revealed abscess formation and post-inflammatory pigmentation. Millimetric scar formation and improved folliculitis-like lesions were observed on both glutei. These complaints started 7 years ago and become more intense and severe by time. Owing to the diagnoses of diabetes mellitus, hypertension, and hyperlipidemia, the patient was monitored for metabolic syndrome. In the cultures taken from the lesions, no growth was seen. A standardized skin surface biopsy of the patient demonstrated demodicosis. The patient was treated with oral metronidazole and topical permethrin lotion, whereupon a pronounced recovery was observed in her clinical condition. In the light of this case, we recommend that patients with HS should be checked for the presence of Demodex spp., and if it is detected, an appropriate treatment should be applied. To our knowledge, this is the first case report presenting the relationship between HS and Demodex infestation.

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.

Papulopustular rosacea and rosacea-like demodicosis: two phenotypes of the same disease?

BACKGROUND: Papulopustular rosacea and rosacea-like demodicosis have numerous similarities, but they are generally considered as two distinct entities, mainly because the causal role of the Demodex mite in the development of rosacea is not yet widely accepted. Several clinical characteristics are traditionally considered to differentiate the two conditions; for example, papulopustular rosacea is typically characterized by central facial papulopustules and persistent erythema, whereas small superficial papulopustules and follicular scales rather suggest rosacea-like demodicosis. However, none of these characteristics is exclusive to either entity. OBJECTIVE: To explore differences in Demodex densities according to clinical characteristics traditionally associated with these two conditions. METHODS: Retrospective, observational, case-control study of 242 patients with central face papulopustules. Demodex densities were measured on two consecutive standardized skin surface biopsies. RESULTS: In the whole cohort, Demodex densities were greater in patients with persistent erythema than in those without. In 132 patients without recent treatment or other facial dermatoses, 120 (91%) had persistent erythema, 119 (90%) small superficial papulopustules and 124 (94%) follicular scales; 116 (88%) simultaneously had clinical characteristics traditionally associated with both papulopustular rosacea and rosacea-like demodicosis. Higher Demodex densities were linked to the presence of follicular scales, but not to papulopustules size, nor to the presence/absence of persistent erythema. CONCLUSION: Our observations highlight the difficulty differentiating between these entities and suggest that rosacea-like demodicosis and papulopustular rosacea should no longer be considered as two separate entities, but rather as two phenotypes of the same disease.

[Cutaneous infections: Pathologist's role in unusual or atypical situations]. / Infections cutanées : place du pathologiste dans les situations inhabituelles ou atypiques.

In infectious pathology, the gold standard consists of the detection of the pathogen within the sample. Identification of the pathogen is often difficult despite the presence of few and inexpensive tools, such, as special stain, immunohistochemistry, or in situ hybridization specific of the pathogen. In infectious pathology, there are morphological signs, which can guide us towards an etiology. We present some clinicopathological examples illustrating rare or unusual situations in cutaneous infectious pathology.

Granulomatous rosacea: a case report.

BACKGROUND: Granulomatous rosacea is a rare chronic inflammatory skin disease with an unknown origin. The role of Demodex follicularum in its pathogenesis is currently proved. CASE PRESENTATION: We report a case of a 54-year-old Moroccan man with a 3-month history of erythematous, nonpruritic papules on the lateral side around the eyes. Dermoscopy and histology confirmed the diagnosis of granulomatous rosacea. CONCLUSIONS: We describe another clinical presentation of granulomatous rosacea with a clinical-dermoscopic-pathological correlation.

Demodicosis in Pediatric Cancer.

Demodicosis is a rare condition that most often occurs in immunocompromised patients. We here describe a boy with T-cell non-Hodgkin lymphoma who developed a facial papulopustular eruption just before finalizing T-cell non-Hodgkin lymphoma treatment. He was treated for several infectious diseases without improvement. Demodicosis was considered and complete resolution was finally reached with topical metronidazole. We conducted a systematic search of all previously described cases of this condition in children with cancer, which showed that almost all demodicosis cases occurred in patients with lymphoreticular malignancies during maintenance chemotherapy. Hence, demodicosis may be seriously considered in antibiotic-resistant facial papulopustular eruptions in this group of patients to prevent delay of adequate treatment.

Two Consecutive Standardized Skin Surface Biopsies: An Improved Sampling Method to Evaluate Demodex Density as a Diagnostic Tool for Rosacea and Demodicosis.

Diagnosing papulopustular rosacea is not always straightforward; no specific diagnostic test is currently available. A high density of Demodex mites is consistently observed in this condition. This retrospective study assesses an improved method for evaluating Demodex density among 1,044 patients presenting to our dermatology practice. The skin was cleaned with ether and Demodex densities were measured in 2 consecutive standardized skin surface biopsies taken from the same site. Mean densities in patients with rosacea and demodicosis were much higher than those in healthy controls and patients with other facial dermatoses. The optimal cut-off values for the 2 biopsies were combined and the resultant criterion (presence of a first biopsy density < 5 Demodex/cm2 or a second biopsy density < 10 Demodex/cm2) enabled confirmation of a diagnosis of rosacea or demodicosis with a sensitivity of 98.7% and specificity of 95.5%, making this a valuable diagnostic tool for dermatologists in routine clinical practice.