Demodex mites in acne rosacea

The hair follicle mites Demodex folliculorum and Demodex brevis and their role in the pathogenesis of rosacea have been the subject of much debate in the past. We studied the prevalence of Demodex mites in facial skin biopsies obtained from 80 patients with rosacea, 40 with facial eczematous eruption and 40 with lupus erythematosus discoides. The mite prevalence in the rosacea group (51%) was significantly higher than in the rest of the study population (eczema 28% and lupus discoides 31%). Demodex mites were found on all facial sites. The most infested areas in the whole study group were the forehead (49%) and the cheeks (44%). Males were more frequently infested (59%) than females (30%). We did not find any significant difference in mite counts of infested follicles between rosacea and the control group. A lympho-histiocytic cell infiltration was seen around the infested hair follicles. Our results suggest that Demodex mites may play a role in the inflammatory reaction in acne rosacea.     

Increased density of Demodex folliculorum and evidence of delayed hypersensitivity reaction in subjects with papulopustular rosacea

BACKGROUND: Rosacea is a common chronic dermatosis that evolves in stages. The mite Demodex folliculorum has been implicated in its obscure aetiopathogenesis. AIM: To evaluate the importance of D. folliculorum in the aetiology and course of rosacea. METHODS: We studied 92 consecutive cases of papulopustular rosacea and 92 age- and sex-matched controls. Prevalence and density of D. folliculorum were estimated by microscopic examination of the expressed follicular content. Histological examination and immunohistochemical study of the inflammatory infiltrate were performed in 10 subjects (five with positive D. folliculorum finding and five with negative finding). RESULTS: D. folliculorum was detected in 83 (90.2%) of the 92 rosacea subjects but only 11(11.9%) of the controls. The mean mite density was 2.03 mites/visual field in the rosacea group (range 0-5, SD = 1.2) and 0.16 mites/visual field (range 0-2, SD = 0.52) in the control group. The difference was statistically significant (P < 0.0001) for both mite prevalence and density. Hair follicle infestation was associated with intense perifollicular infiltrate of predominantly (90-95%) CD4 helper/inducer T cells. We observed an increased number of macrophages and Langerhans cells only in those subjects with a positive D. folliculorum finding. CONCLUSIONS: Although Demodex mites do not seem to be the cause of rosacea, they may represent an important cofactor, especially in papulopustular rosacea. Immunohistochemical findings suggest that a delayed hypersensitivity reaction, possibly triggered by antigens of follicular origin, probably related to D. folliculorum, may occur, stimulating progression of the affection to the papulopustular stage.     

Mite-related bacterial antigens stimulate inflammatory cells in rosacea

BACKGROUND: Patients with papulopustular rosacea have a higher density of Demodex folliculorum mites on their faces than normal subjects but the role, if any, of their mites in initiating inflammation is disputed. Selective antibiotics are effective in reducing the inflammatory changes of papulopustular rosacea, but their mode of action is unknown. OBJECTIVES: To investigate whether a D. folliculorum-related bacterium was capable of expressing antigens that could stimulate an inflammatory immune response in patients with rosacea. METHODS: A bacterium (Bacillus oleronius) was isolated from a D. folliculorum mite extracted from the face of a patient with papulopustular rosacea, and was investigated further. RESULTS: This bacterium produced antigens capable of stimulating peripheral blood mononuclear cells proliferation in 16 of 22 (73%) patients with rosacea but only five of 17 (29%) control subjects (P = 0.0105). This antigenic preparation was fractionated into 70 subfractions and the proteins in each fraction were visualized by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Western blot analysis revealed the presence of two antigenic proteins of size 62 and 83 kDa in fractions when probing with sera from patients with rosacea. No immunoreactivity to these proteins was recorded when probing with sera from control patients. Two-dimensional electrophoretic separation was used to isolate these proteins and matrix-assisted laser desorption/ionization time-of-flight analysis was employed to identify the relevant peptides. The 62-kDa immunoreactive protein shared amino acid sequence homology with an enzyme involved in carbohydrate metabolism and signal transduction while the 83-kDa protein was similar to bacterial heat shock proteins. CONCLUSIONS: Antigenic proteins related to a bacterium (B. oleronius), isolated from a D. folliculorum mite, have the potential to stimulate an inflammatory response in patients with papulopustular rosacea.     

Nosologic position of demodicidosis in humans

In 20 patients with rosacea and rosacea-like eruptions Demodex folliculorum mites were found in high numbers within lesional skin. In one patient Demodex folliculorum could be demonstrated in pits and burrows in the epidermis of the scalp. In other instances the mouth parts of the mites were closely related to the follicular epithelium. Recent parasitologic findings showed that in spite of their name (Demodex = "sebaceous worm") the mites derive their nutritive requirements from cellular proteins obtained by epithelial destruction. To clarify the pathogenetic significance of hair follicle mites in man as suggested by these histological findings as well as their known ability to form organisational centers of foreign body granulomas, further epidemiologic and immunologic studies are needed. Topical antiparasitic agents did not offer any therapeutic advantage over traditional preparations used for rosacea and seborrheic dermatitis.     

Permethrin 5% cream versus metronidazole 0.75% gel for the treatment of papulopustular rosacea. A randomized double-blind placebo-controlled study

BACKGROUND: Permethrin 5% cream used against human ectoparasites suggests that it may be effective in papulopustular rosacea. METHODS: This study included 63 patients diagnosed as having papulopustular rosacea based on the clinical and histological findings. Patients were randomly assigned into permethrin (n = 23), metronidazole (n = 20) and placebo (n = 20) groups. Scores of erythema, telangiectasia, edema and rhinophyma and the numbers of papules, pustules, inflammatory nodules and Demodex folliculorum were determined. Twenty-three patients were given permethrin 5% cream (Zalvor 5% skin cream, 20 patients metronidazole 0.75% gel (Roza gel and 20 patients placebo cream (Basis cream, in packages looking identical to those of metronidazole and permethrin creams, and were recommended to apply them to their faces twice a day. All patients were also given SPF 20 cream for protection against sunlight. Two months of treatment were planned, and the patients were invited to the clinic for fortnightly controls. Scores of erythema, telangiectasia, edema and rhinophyma and the numbers of papules, pustules, inflammatory nodules and D. folliculorum were recorded at each visit. The mean scores of erythema and the mean numbers of papules, pustules and D. folliculorum were determined at baseline and on days 15, 30, 45 and 60. Side effects were also detected. RESULTS: The effect of permethrin 5% cream on D. folliculorum was superior to that of metronidazole 0.75% gel. The effect of permethrin 5% cream on erythema and papules was found to be more effective than placebo and as effective as metronidazole 0.75% gel. However, it had no effect on telangiectasia, rhinophyma and pustules. CONCLUSION: It can be concluded that the application of permethrin 5% cream twice daily for 2 months can be as effective and reliable as metronidazole in the treatment of rosacea and a greater benefit can be gained when it is combined with other systemic and/or topical treatments.     

Pathogenesis associated with hair follicle mites (Demodex spp.) in Australian Aborigines

Demodex folliculorum and D. brevis are found in different habitats in the skin: the former in the hair follicles, the latter in the sebaceous glands. Both seem minor pathogens--merely harvesting the cells of their respective habitats. D. folliculorum was found aggregated (all stages) and plugging the follicular orifices; D. brevis, on the other hand, was usually solitary. In one case marked degeneration of the sebaceous gland, with leukocyte invasion, was associated with D. brevis. No correlations were discovered between either of these species and the gross condition of the skin. Positive samples were obtained from both mainland and island populationf of Aborigines. Incidence values obtained were 66.6% for males and 80% for females; in the latter, the sample was small (5) and their ages over 34 years.     

The histopathology of alopecia areata in vertical and horizontal sections

Alopecia areata (AA) is a relatively common disease affecting 1.7% of Americans by the age of 50 years. The diagnosis is usually made on clinical grounds. In some cases the diagnosis is elusive and biopsies are necessary. In other cases biopsies are useful from a prognostic point of view to determine whether there are enough follicles left for possible future regrowth. In view of the active research being conducted into AA, biopsies provide valuable material for further investigation. The diagnosis of AA is improved by the use of horizontal sections in addition to or instead of vertical sections of scalp biopsies. The histopathologic features favoring the diagnosis of AA include peribulbar and intrabulbar mononuclear infiltrates, degenerative changes in the hair matrix, decreased numbers of terminal anagen follicles, increased numbers of terminal catagen and telogen follicles, an increased number of follicular stelae, an increased number of miniaturized vellus hair follicles, and pigment incontinence of hair bulbs and follicular stelae. Follicular counts with horizontal sections are particularly helpful in making the diagnosis of AA when the biopsy has been taken between acute episodes and the characteristic peribulbar inflammatory infiltrate is absent.     

Clinical and laboratory study of rosacea in northern Greece

Background Numerous factors have been implicated in the pathogenesis of rosacea, which remains obscure. Objectives To examine the epidemiological characteristics of rosacea patients, the histopathological alterations, the prevalence of gastric Helicobacter pylori infection and the role of ultraviolet radiation, to detect the presence of Demodex folliculorum on affected skin and to elucidate the immunological nature of this disorder. Methods The study included 100 patients with rosacea. Each patient was assessed with a clinical, haematological, biochemical and histological examination; serology test for the detection of antibodies against H. pylori; direct immunofluorescence on perilesional, sun exposed skin and indirect immunofluorescence with monkey oesophagus as a substrate; antinuclear antibody titre and a skin surface biopsy to search for Demodex folliculorum. Results Women were more frequently affected. Half of our patients were 51–70 years old. About two‐thirds were phototypes I and II and 73% complained of worsening of conditions after sun exposure. An almost permanent histopathological feature was solar elastosis. Higher prevalence of H. pylori was not established. Prevalence and mean density of Demodex folliculorum were significantly increased in rosacea patients. Direct and indirect immunofluorescence tests were positive in 6.4% and 6.7% respectively. Antinuclear antibody titres were found in 21.1%. Conclusions Our results suggest the pivotal role of chronic sun exposure in the pathogenesis of rosacea. Demodex folliculorum represents a significant cofactor that may contribute to the transition of the disease from a vascular to an inflammatory stage. The low positive results of direct and indirect immunofluorescence do not support a potential autoimmune role in the development of rosacea.     

Rosacea-like demodicidosis in an immunocompromised child

Demodex folliculorum is a saprophytic mite of the human pilosebaceous unit. It is rarely found in children. It has been implicated in the development of follicular pityriasis, rosacea-like demodicidosis, pustular folliculitis, blepharitis, and granulomatous rosacea. We describe a 4-year-old boy who developed asymptomatic facial lesions that histologically corresponded to demodicidosis. He was in clinical remission of acute lymphoblastic leukemia and currently receiving maintenance chemotherapy. Exanthems related to D. folliculorum are rare in children. Most cases occur in immunocompromised patients and the clinical and histologic findings are diverse. A differential diagnosis should be established with rosacea and perioral dermatitis. The role of Demodex in the pathogenesis of these disorders is controversial. Immunosuppression might increase the number of mites, favoring an inflammatory reaction, or there could exist an impaired cutaneous immunologic response to the parasites.     

Kerion and dermatophytic granuloma. Mycological and histopathological findings in 19 children with inflammatory tinea capitis of the scalp

BACKGROUND: Inflammatory tinea capitis or kerion is the result of a hypersensitivity reaction to a dermatophytic infection. Majocchi's granuloma, in contrast, usually begins as a suppurative folliculitis and culminates in a granulomatous reaction. OBJECTIVES: To present clinical, mycological and histopathological findings for 19 cases of kerion of the scalp in children. METHODS: Nineteen children were investigated (14 boys and five girls) with a mean age of 6.5 years. A potassium hydroxide (KOH) exam and culture in Sabouraud dextrose agar were performed, followed by a biopsy with hematoxylin and eosin, periodic acid-schiff (PAS) and Gomori-Grocott stains. The same investigations were carried out in four control cases of noninflammatory tinea capitis. RESULTS: Clinical history varied from 2 to 16 weeks (mean 6.6 weeks). Diagnosis was confirmed by a positive KOH exam: all cases except one had a positive culture. The following dermatophytes were isolated: Microsporum canis (32%), Trichophyton mentagrophytes (27%), Trichophyton tonsurans (21%), Trichophyton rubrum (10%) and Microsporum gypseum (5%). The histopathological findings were: suppurative folliculitis (SF) 11%, SF plus suppurative dermatitis 37%, suppurative and granulomatous dermatitis (SGD) 26% and SGD plus fibrosing dermatitis 26%. Fungi were observed in 63% of the histopathological sections. Perifollicular infiltrates (PF) around the parasitized hair follicles were identified in the four noninflammatory control cases due to M. canis. CONCLUSIONS: Kerion Celsi is an inflammatory or suppurative type of tinea capitis caused by zoophylic dermatophytes (M. canis and T. mentagrophytes), but also by antrophophylic (T. tonsurans and T. rubrum) and geophylic (M. gypseum) dermatophytes. Histopathological findings showed a spectrum from mild suppurative folliculitis to dense granulomatous infiltrates without a clear relationship with the clinical features.     

Histopathology of hypotrichosis with juvenile macular dystrophy

Hypotrichosis with juvenile macular dystrophy (HJMD) (MIM 601553) is a rare disorder characterized by the paucity of hair and progressive macular degeneration leading to blindness. We have recently shown that mutations in the CDH3 gene encoding P-cadherin are the proximal cause of HJMD. The present study was performed to establish the histopathology of this disorder. 4 mm punch scalp biopsies from 6 HJMD patients aged 9 to 21 years were studied. All patients had a homozygous missense mutation resulting in a single amino acid substitution at position 503 of P-cadherin amino acid sequence (R503H). The total number of hair follicles varied between 6 and 14 per histologic section. More catagen-telogen hair follicles were observed in five cases, and an increased ratio of vellus hair follicles to terminal hair follicles was observed in two cases. There were no signs of inflammation or scarring. Thus, the most frequent histologic abnormality in HJMD resembles chronic telogen effluvium. This suggests that absence of functional P-cadherin interferes with normal hair cycle.     

Rapid, severe repigmentation of congenital melanocytic naevi after curettage and dermabrasion: histological features

BACKGROUND: Curettage and dermabrasion are effective in treating giant congenital melanocytic naevi (GCMN). We report two patients with rapid, severe postoperative repigmentation. To the best of our knowledge this is the first report on the histological features of such patients. OBJECTIVES: We wish to call attention to histological features that may cause rapid, severe repigmentation after curettage and dermabrasion of medium to giant CMN. PATIENTS/METHODS: From 1998 to 2002, we treated 23 patients with medium to giant CMN with curettage and dermabrasion. Patients being treated ranged in age from 1 month to 19 years. Histological samples were taken from the centre of naevi in all patients during surgery. Histological types were 12 intradermal and 11 compound. Follow-up after curettage lasted at least 3 years. RESULTS: Among our 23 patients only two showed repigmentation soon after surgery. Histological sections from these two patients indicated naevoid cells in the deep dermis along hair follicles or sebaceous glands. However, no such pigmented naevoid cells along hair follicles were observed in samples from patients successfully treated with curettage and dermabrasion with less repigmentation. CONCLUSIONS: Although we saw only two cases of repigmentation soon after curettage and dermabrasion, we suspect a correlation between pigmented naevoid cells around hair follicles and repigmentation. If histological sections of skin biopsies show pigmented cells along hair follicles in the deep dermis, other treatments such as total skin resection followed by skin grafting or tissue expansion may be better choices than curettage or dermabrasion.     

毛发扁平苔藓三例分析

目的 探讨毛发扁平苔藓的临床和组织病理特征。方法 分析3例毛发扁平苔藓患者的临床、组织病理学特征。结果 3例患者均为女性,平均年龄49岁。1例患者临床表现为额部、顶部及枕部大面积斑片状脱发,2例表现为头皮不规则斑片状脱发及皮肤萎缩。1例患者除头发外,眉毛、腋毛亦脱落。组织病理均为毛囊壁基底层细胞液化变性及淋巴细胞浸润。1例血管附件周围亦可见少量淋巴细胞浸润。结论 毛发扁平苔藓可仅累及头皮,亦可累及全身其他部位皮肤,多表现为头皮斑片状脱发伴皮肤萎缩。病理学典型改变为毛囊基底细胞液化变性,淋巴细胞浸润。     

Three dimensional distribution of Propionibacterium acnes biofilms in human skin

Propionibacterium acnes is regarded as a common member of the human skin microbiota, often occurring in biofilms. Little is known about the size of bacterial biofilms in hair follicles as a few sections of biopsy tissue are routinely evaluated. Transversal sectioning provides a better opportunity for histological analyses of hair follicles which can be followed through the different morphological levels. Direct visualization of P. acnes biofilms in hundreds of consecutive sections allowed insight into the 3D distribution in human hair follicles as well as investigating the depth of biofilm distribution within hair follicles. Four distinct colonization patterns of P. acnes biofilms were revealed. Results have shown that an individual P. acnes biofilm can spread for 1900 μm in a terminal hair follicle. This information can be of help while designing potential antibiofilm treatment.     

Psoriasiform type of lichen scrofulosorum: clue to disseminated tuberculosis

We present a 16-year-old girl with tuberculosis of the lungs, lymph nodes, and liver, who had extensive inflammatory lesions with pustules, which resembled psoriasis. A skin biopsy showed extensive tuberculoid granulomas surrounding hair follicles, consistent with lichen scrofulosorum. Antitubercular therapy led to resolution of skin lesions. This severe inflammatory type of lichen scrofulosorum is extremely rare.     

斑秃毛囊退行性变及局部炎症细胞浸润的研究进展

斑秃是一种非瘢痕性的炎症性脱发性疾病,病情多能自限,但容易复发。斑秃发病机制不明,组织病理上表现为生长期毛囊周围炎症浸润及毛囊退行性变两个部分。目前研究认为,内外源因素作用于遗传易感人群引起生长期毛囊深层周围炎症细胞浸润,浸润的炎症细胞及细胞因子、神经肽等形成恶性循环,循环结局为毛囊上皮细胞凋亡,大批毛囊同时陕速进入退行期,导致斑秃发生。     

The management of rosacea

Rosacea is a multiphasic disease which is associated with flushing, erythrosis, papulopustular rosacea and phymas; each phase is likely to have its own treatment. Flushing is better prevented rather than treated, and its etiology investigated. Beta-blockers, atenolol in particular, are worthy of prophylactic trials examining their efficacy in treating the flushing associated with rosacea. Currently, clonidine is the only drug available for the treatment of flushing. Treatment for erythrosis includes topical and systemic therapies. Metronidazole 1% cream and azelaic acid 20% cream have been reported to reduce the severity score of erythema. The systemic treatment of erythrosis is based on the association of Helicobacter pylori with rosacea. However, this role is still being debated. Eradication of H. pylori can be achieved using a triple therapy regimen lasting 1 to 2 weeks [omeprazole and a combination of two antibacterials (a choice from clarithromycin, metronidazole or amoxicillin)]. Both the flashlamp-pumped long-pulse dye laser and the potassium-titanyl-phosphate laser may be used in the treatment of facial telangiectases. Both systemic and topical remedies may be used to treat the papulopustules of rosacea. Systemic treatment includes metronidazole, doxycycline, minocycline, clarithromycin and isotretinoin, while topical treatment is based on metronidazole cream and gel. The presence of Demodex folliculorum is important in the inflammatory reaction, whether it is pathogenetic or not. Crotamiton 10% cream or permethrin 5% cream may be useful medications for papulopustular rosacea, although they are rarely successful in eradicating D. folliculorum. Oral or topical ivermectin may also be useful in such cases. Ocular involvement is common in patients with cutaneous rosacea and can be treated with orally administered or topical antibacterials. Once rhinophyma starts to be evident, the only way to correct it is by aggressive dermatosurgical procedures. Decortication and various types of lasers can also be used. Associated conditions, such as seborrheic dermatitis and possible contact sensitizations, deserve attention.     

Sheep vibrissa dermal papillae induce hair follicle formation in heterotypic skin equivalents

Cultured skin equivalents were constructed by combining keratinocytes, outer root sheath cells or isolated epidermis, in vitro, with a matrix composed of collagen and cultured fibroblasts. When equivalents were grafted on to host animals, the epidermis thickened considerably, and tongues of cells penetrated the dermis, giving the dermal/epidermal junction a deeply sculptured profile. No cutaneous appendages were found in these grafts. We explored the possibility of inducing hair follicles by incorporating ovine hair follicle dermal papillae into constructs composed of an isolated epidermal sheet and a contracted dermal equivalent. In vitro, no morphogenetic changes associated with follicle formation were observed in the recombinants, but when grafted on to nude mice, follicle-like structures were identified. The follicles were large, and had developed adjacent to the epidermis, indicating that the matrix environment of the induced follicles may not have been compatible with the downgrowth of the epidermal plugs normally observed during follicle formation in living skin. Nevertheless, in histological sections, the induced structures displayed many of the morphological characteristics of follicles in vivo, including the production of keratinized hairs. These results indicate that skin equivalents provide a useful model for the study of the chemical and structural features of matrices that facilitate hair follicle development.     

淋巴瘤伴发皮肤肉芽肿的现象及其意义

淋巴瘤可伴发皮肤肉芽肿,其模式主要有两种:一种是淋巴瘤的特异性皮损中出现肉芽肿反应,例如肉芽肿性蕈样肉芽肿和肉芽肿性皮肤松弛症;另一种是淋巴瘤出现非特异的肉芽肿性皮损,主要见于一些系统性淋巴瘤.其组织病理学类型可为结节病样、环状肉芽肿样、结核样等.其机制及其与预后的关系尚不明确.肉芽肿形成可能是造成某些淋巴瘤特殊临床表现的原因,也容易掩盖淋巴瘤的真实面目,在临床和组织学诊断上需谨慎.     

关于毛囊蠕形蜻对酒渣鼻致病性的商榷

为探讨酒渣鼻是否为毛囊虫所致.我们选择了100例典型的丘疹、脓疤期酒渣鼻患者,应用灭滴灵进行治疗观察.治疗前,全部患者均作了鼻部皮脂腺和面部脓泡内名毛囊虫检查,93例鼻部皮脂内毛囊虫为阳性,伺时有87例伴有脓危内容毛囊虫阳性;7例鼻部皮脂及面部脓疙内容毛囊虫皆为阴性.经用灭滴灵治疗2-4周后,无论毛囊虫阳性或阴性的病例,均获良好效果.临床治愈的病例,凡毛囊虫阳性者,直到治愈后毛囊虫始终皆为阳性,且均有活力.由此可见,酒渣鼻并非是毛囊虫引起的.