Interventions for rosacea based on the phenotype approach: an updated systematic review including GRADE assessments.

BACKGROUND: Rosacea is a common chronic facial dermatosis. Classification of rosacea has evolved from subtyping to phenotyping. OBJECTIVES: To update our systematic review on interventions for rosacea. METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index and ongoing trials registers (March 2018) for randomized controlled trials. Study selection, data extraction, risk-of-bias assessment and analyses were carried out independently by two authors. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to assess certainty of evidence. RESULTS: We included 152 studies (46 were new), comprising 20 944 participants. Topical interventions included brimonidine, oxymetazoline, metronidazole, azelaic acid, ivermectin and other topical treatments. Systemic interventions included oral antibiotics, combinations with topical treatments or other systemic treatments. Several studies evaluated laser or light-based treatment. We present the most current evidence for rosacea management based on a phenotype-led approach. CONCLUSIONS: For reducing temporarily persistent erythema there was high-certainty evidence for topical brimonidine and moderate certainty for topical oxymetazoline; for erythema and mainly telangiectasia there was low-to-moderate-certainty evidence for laser and intense pulsed light therapy. For reducing papules/pustules there was high-certainty evidence for topical azelaic acid and topical ivermectin; moderate-to-high-certainty evidence for doxycycline 40 mg modified release (MR) and isotretinoin; and moderate-certainty evidence for topical metronidazole, and topical minocycline and oral minocycline being equally effective as doxycycline 40 mg MR. There was low-certainty evidence for tetracycline and low-dose minocycline. For ocular rosacea, there was moderate-certainty evidence that oral omega-3 fatty acids were effective and low-certainty evidence for ciclosporin ophthalmic emulsion and doxycycline.

Recalcitrant psoriasiform dermatosis of the face: Is it related to pityriasis rubra pilaris?

BACKGROUND: There are patients with recalcitrant psoriasiform plaques that do not fit into conventional categories of facial dermatoses. Our study aims to describe the clinicopathological characteristics of several patients with a unique presentation of persistent psoriasiform facial rashes. METHODS: This retrospective cross-sectional study analyzed clinical and histological data of known cases of recalcitrant psoriasiform dermatosis of the face diagnosed at National Skin Centre, Singapore, over 10 years. RESULTS: There were 8 Chinese patients with mean age at onset of 29 years. Majority had pink to pink-orange well-defined plaques with dry scale (n = 6, 75%), distributed mostly on the cheeks (100%) and chin (n = 7, 88%). Hyperkeratosis, parakeratosis, preserved granular layer and psoriasiform hyperplasia were showed in all biopsies. Other common findings included subtle subcorneal acantholysis, "checkerboard" alternating ortho-/parakeratosis, vacuolated keratinocytes and follicular plugging. All patients showed little treatment response. One patient eventually developed features of type II pityriasis rubra pilaris (PRP). Our study was limited by its small sample size and lack of a pre-existing diagnostic code. CONCLUSIONS: This recalcitrant psoriasiform facial dermatosis seems to be a distinct entity, with consistent and reproducible clinical features and a PRP-like histology, bearing some resemblance to the recently described condition-facial discoid dermatosis.

Classification of facial vitiligo: A cluster analysis of 473 patients.

Vitiligo has a substantial negative impact on quality of life in affected patients, especially those with the involvement of the face. However, the current system can barely distinguish between specific patterns of facial involvement except for the segmental type when focusing only on facial lesions. We classified facial vitiligo into three distinct subtypes using cluster analysis based on facial topography (n = 473): centrofacial vitiligo (72.9%), panfacial vitiligo (18.0%), and hairline vitiligo (9.1%). Centrofacial vitiligo was the most common type and is thought to comprise the typical facial involvement of generalized vitiligo. Panfacial vitiligo was a distinct subtype with onset in old age and less involvement of other body parts. Hairline vitiligo was another distinct subtype with onset in old age and a poor response to conventional phototherapy. A relevant classification system could help us to explore the causes, anticipate the prognosis, and manage the condition in patients with vitiligo.

Actinic keratoses show variable histological basal growth patterns - a proposed classification adjustment.

BACKGROUND: Common histological classification schemes of actinic keratoses (AK) do not evaluate growth patterns at basal epidermal aspects of AK. Until now, the importance of basal epidermal growth patterns of AK has not been studied. OBJECTIVE: To investigate the extent of atypical keratinocytes throughout the epidermis and variation in basal growth patterns of AK. METHODS: AK lesions occurring on the head/face from patients seen in routine practice were assessed histologically. We determined histological grade (AK I-III), basal growth patterns of atypical keratinocytes (crowding, budding and papillary sprouting) and accompanying parameters. RESULTS: Of the 246 lesions included, 28.0% were histologically classified as AK I, 46.7% as AK II and 25.2% as AK III. Approximately 26.4% of the basal growth patterns were classified as crowding (pro I), 49.6% as budding (pro II), 17.9% as papillary sprouting (pro III) and 6.1% without basal directed growth. No significant correlation of the histological AK I-III grading and underlying growth patterns was observed (P = 0.4666). However, adnexal structure involvement (OR = 2.37; 95% CI 1.21-4.65), infiltration (OR = 2.53; 95% CI 1.31-4.90) and increased number of vessels (OR = 2.56; 95% CI 1.42-4.65) were independent positive predictive markers for pro II and pro III basal growth patterns. CONCLUSIONS: Basal growth patterns (pro I-III) in AK do not correlate with the established AK I-III histological grading system. Besides the degree of upward extension, varying degrees of downward extension exist. Histological classification should consider both, upwards and downward growth patterns when assessing AK.

Classification by causes of dark circles and appropriate evaluation method of dark circles.

BACKGROUND: Dark circles refer to a symptom that present darkness under the eyes. Because of improvement in the quality of life, the dark circles have been recognized as one of major cosmetic concerns. However, it is not easy to classify the dark circles because they have various causes. METHODS: To select suitable instruments and detailed evaluation items, the dark circles were classified according to the causes through visual assessment, Wood's lamp test, and medical history survey for 100 subjects with dark circles. After the classification, were newly recruited for instrument conformity assessment. Through this, suitable instruments for dark circle evaluation were selected. We performed a randomized clinical trial for dark circles, a placebo-controlled double-blind study, using effective parameters of the instruments selected from the preliminary test. RESULTS: Dark circles of vascular type (35%) and mixed type (54%), a combination of pigmented and vascular types, were the most common. Twenty four subjects with the mixed type dark circles applied the test product (Vitamin C 3%, Vitamin A 0.1%, Vitamin E 0.5%) and placebo on randomized split-face for 8 weeks. The effective parameters (L*, a, M.I., E.I., quasi L*, quasi a* and dermal thickness) were measured during the study period. Result showed that the L* value of Chromameter(®) , Melanin index (M.I.) of Mexameter(®) and quasi L* value obtained by image analysis improved with statistical significance after applying the test product compared with the placebo product. CONCLUSION: We classified the dark circles according to the causes of the dark circles and verified the reliability of the parameter obtained by the instrument conformity assessment used in this study through the efficacy evaluation. Also based on this study, we were to suggest newly established methods which can be applied to the evaluation of efficacy of functional cosmetics for dark circles.

Clinical evaluation of 368 patients with nasal rosacea: subtype classification and grading of nasal rosacea.

BACKGROUND: The clinical features of nasal rosacea have not been described in detail. OBJECTIVE: To describe the clinical features of nasal rosacea. METHODS: 599 patients were classified into those with rosacea in both the nasal and extra-nasal areas (group A), localized nasal rosacea (group B) and rosacea without nasal involvement (group C). RESULTS: The mixed subtype was more common in group A (n = 337) than in group C (n = 231). The severity score was higher in group A than in group C. Erythematotelangiectatic rosacea was the most common subtype in group B (n = 31) and was more common in group B than in group A. Rosacea mainly affected the lower half of the nose in group B, but affected the entire nose in group A. CONCLUSION: Nasal involvement may be an index of severe rosacea. Localized nasal rosacea is a separate spectrum with different clinical features.

Hypochromic vitiligo: delineation of a new entity.

BACKGROUND: Hypochromic vitiligo is a rare entity that has been reported only twice under the term 'vitiligo minor', with an absence of clear delineation. OBJECTIVES: To delineate hypochromic vitiligo through a case series of patients with typical bilateral hypopigmented lesions affecting the face and trunk. METHODS: This is a retrospective multicentric evaluation study conducted in eight departments of dermatology in France, Belgium, Senegal and Saudi Arabia. RESULTS: Twenty-four cases of hypochromic vitiligo were identified. Fourteen were men and 10 women. The mean age at diagnosis was 35·4 years (range 8-66). Strikingly, all patients were dark skinned, with skin types V and VI. The pattern of distribution was highly similar in most of the patients (18 of 24), with involvement of the face and neck area predominating on seborrhoeic areas associated with multiple isolated hypopigmented macules involving predominantly the scalp. The retrospective nature of this study is its main limitation. CONCLUSIONS: Hypochromic vitiligo is not yet part of a conventional classification. The disease seems to be limited to individuals with dark skin types. Hypopigmented seborrhoeic face and neck involvement associated with hypopigmented macules of the trunk and scalp is the hallmark of the disease.

Soft tissue reactions in patients with bone anchored hearing aids.

AIMS: To establish the incidence and correlation between the degree of soft tissue reaction and the body mass index (BMI) according to age and gender after a bone anchored hearing aid (BAHA) implant. METHODS: We did a 1-9-year follow-up for the all the patients who underwent surgery in our department with BAHA implant system. Soft tissue reactions were classified in accordance with the Holgers classification on regular patient visits. BMI was calculated for each patient, and changes were recorded at least once a year. RESULTS: 47 patients were evaluated. 58% were operated on for chronic otitis with mixed or conductive hearing loss; 20% had unilateral or bilateral atresia and 16% had single sided deafness (SSD); other indications were otosclerosis and syndromic patients. The grade of Holgers classification significantly correlated at a 0.001 level with BMI (Spearmans rho 0.452). Holgers grade also differed significantly between the sexes-skin reactions in females were less frequent. An ANOVA test did not reveal any statistical difference between patients with dissimilar indications for BAHA. CONCLUSION: If performed carefully, BAHA surgery produces a favorable outcome. The Holgers grade may change as time passes. If skin reactions appear, they can be treated through local or systemic therapy, and they may turn into a normal grade. Adipose patients should be treated with special care because they are more prone to soft tissue reactions.

Biopsies of facial dermatoses made simple.

CONTEXT: Biopsy of the face is rarely done for inflammatory skin diseases, unless the entire process is confined to the face. OBJECTIVE: We hypothesized that facial dermatitis has a differential diagnosis that is more limited than the differential diagnosis of inflammatory skin diseases that affect other parts of the body. To our knowledge, the classification of inflammatory skin diseases occurring on the face has never been conducted before in the English literature. DESIGN: The most-recent 100 facial biopsies of inflammatory skin conditions were retrieved from our files, and the cases were categorized into the main inflammatory skin patterns. RESULTS: Forty-seven cases (47%) were categorized as interface dermatitis, 2 cases (2%) as psoriasiform dermatitis, 11 cases (11%) as spongiotic dermatitis, 16 cases (16%) as diffuse and nodular dermatitis, 8 cases (8%) as perivascular dermatitis, 14 cases (14%) as folliculitis and perifolliculitis, 1 case (1%) as panniculitis, and 1 case (1%) as fibrosing dermatitis. The number of diagnostic entities represented within each of these patterns was small. CONCLUSIONS: We believe that facial dermatitis should have its own more-circumscribed differential diagnosis. From a practical viewpoint, many of the inflammatory skin diseases that affect other parts of the body should be excluded from the differential diagnosis after the tissue is determined to be from a facial skin biopsy, and others should not be considered unless the biopsy is from the face.

Human demodicosis: revisit and a proposed classification.

Human Demodex mites (Demodex folliculorum and Demodex brevis) hold a high rank in the evolutionary and phylogenetic hierarchy of the skin microbiome, although in most people their presence is of no consequence. While human demodicosis is a skin disease sui generis, it can mimic many other inflammatory dermatoses, such as folliculitis, rosacea and perioral dermatitis, leading to unspecific and confusing descriptions in the literature. Here, we propose to classify human demodicosis into a primary form and a secondary form, which is associated mainly with immunosuppression. The clinical manifestations of primary demodicosis may include (i) spinulate demodicosis, currently known as pityriasis folliculorum, involving sebaceous hair follicles without visible inflammation; (ii) papulopustular/nodulocystic or conglobate demodicosis with pronounced inflammation affecting most commonly the perioral and periorbital areas of the face; (iii) ocular demodicosis, inducing chronic blepharitis, chalazia or, less commonly, keratoconjunctivitis; and (iv) auricular demodicosis causing external otitis or myringitis. Secondary demodicosis is usually associated with systemic or local immunosuppression. Treatment is only weakly evidence based, and the most effective concentrations of acaricides remain to be determined. Optimization of an in vitro or ex vivo culture model is necessary for future studies. Endosymbiosis between certain bacteria and Demodex mites in the pathogenesis of demodicosis deserves more attention. Further clinical observations and experiments are needed to prove our hypothesis.

Erythema dose--a novel global objective index for facial erythema by computer-aided image analysis.

BACKGROUND: Facial erythema is a common but morbid condition caused by several inflammatory disorders. Since most of the current severity indexes lack objectivity and global assessment, the computer-aided image analysis (CAIA) has been suggested. OBJECTIVE: The purpose of this study is to compare the validity and efficacy of novel CAIA erythema index - erythema dose (ED) with two other CAIA indexes. METHODS: For mild, moderated and severe erytherotelangiectatic rosacea patients, their photographs of right cheek were assessed with red-blue difference index in image (RBI), a*, and ED. For each index, the differences between severity groups were analyzed. The correlations between the three indexes were evaluated. To evaluate the capability of differentiating the pathologic erythema from the red component of the normal skin, each index was calculated at both the erythema and normal area. RESULTS: The a* and ED significantly changed according to the severity, while the RBI did not. The ED was different between both mild-moderate and moderate-severe, while the a* only between mild-moderate. There was a strong positive correlation between a* and ED. The difference between erythema and normal skin was more prominent in ED than in a*. CONCLUSION: We confirmed that the ED is well correlated with both subjective assessment, as well as the other CAIA index a*. The ED has the advantage of specifically visualizing and analyzing the pathologic erythema.

Clinical analysis and classification of dark eye circle.

BACKGROUND: Dark eye circle (DEC) is a common problem that usually lacks detailed classification in the etiology and structural variations. A newly-developed DEC Assessment Score using Wood's lamp and ultrasonogram will provide a more precise evaluation of DEC for improving treatment results. MATERIALS AND METHODS: Sixty-five cases, including eight males and 57 females with a mean age of 38.9 years, were enrolled. DEC were classified into pigmented (brown), vascular (blue to purple), structural, and mixed type by Wood's lamp and ultrasonogram. A scoring system with nine parameters, including brown hue, pigmented lesions, blue/pink/purple hue, periorbital puffiness, shadow hue, infraorbital palpebral bags, infraorbital grooves, blepharoptosis, and skin type, was used for clinical evaluation. RESULTS: Pigmented, vascular, structural, and mixed types of DEC represented 5%, 14%, 3%, and 78%, respectively. Thirty-three cases with periorbital puffiness were found to have higher "pre-septal thickness" than those of 20 controlled cases (P = 0.032). Fourteen patients with infraorbital palpebral bags were proved to have protruded retroseptal fat pads by ultrasonography. CONCLUSION: Pigmentation and vascular and structural components may play important roles in DEC. Detailed classification of DEC types will access physicians in the decision of appropriate therapeutic modalities.

Orofacial tuberculosis--a 16-year experience with 46 cases.

PURPOSE: The aim of this study was to evaluate clinical signs and symptoms of orofacial tuberculosis, with an emphasis on the importance of histologic diagnosis. Based on an evaluation of 46 patients, Andrade's classification is presented with a novel 10-point protocol for the management of orofacial tuberculosis. MATERIALS AND METHODS: Forty-six patients were evaluated for orofacial tuberculosis over 16 years (1996 through 2011). All 46 patients were managed with a 10-point protocol for the care of orofacial tuberculosis. RESULTS: Forty-six cases with a positive diagnosis of orofacial tuberculosis were confirmed by histopathologic and other investigations specified in the 10-point protocol for the management of orofacial tuberculosis. The male:female ratio was 0.917, with no gender predilection. Most cases were seen in the second and third decades of life. A large number of patients (n = 22) presented with a lesion in relation to the angle of the mandible. CONCLUSIONS: In a tuberculosis-prevalent country such as India, it is very important to be aware of tubercular lesions involving the orofacial region. Andrade's classification of orofacial tuberculosis helped classify different forms of tubercular lesions that may involve the orofacial region. The 10-point protocol formulated and applied to all 46 cases proved successful in the management of these cases.

Nosology and therapeutic options for lupus miliaris disseminatus faciei.

Lupus miliaris disseminatus faciei (LMDF) is a distinctive facial eruption of a debatable nosology, unknown etiology and spontaneously resolving course albeit with scarring. The aim of this study was to present the clinico-histopathological features, the rationale for treating and therapeutic response in patients with LMDF treated with different agents, and to attempt to clarify its nosology. Clinical details and demographic data of 29 biopsy-proven cases of LMDF were studied. Laboratory work up included complete blood count, erythrocyte sedimentation rate, tuberculin testing, chest X-ray, serum calcium levels and serum angiotensin-converting enzyme levels. Special stains like Ziehl-Neelsen, periodic acid Schiff and reticulin staining were used, and acid-fast bacilli culture was performed in each patient. The patients were treated with oral minocycline, dapsone, prednisolone and isotretinoin as monotherapeutic agents, or with a combination of oral dapsone plus prednisolone, and oral dapsone plus topical tacrolimus. Six patients had extrafacial lesions. Histological analysis revealed three different patterns: tuberculoid granuloma with central caseation necrosis in 20 patients; sarcoidal-like granuloma in six patients; and non-specific localized perifollicular lymphohistiocytic infiltrate in three patients. Nine out of 11 patients treated with minocycline did not respond, whereas dapsone and low dose prednisone alone or in combination produced good results. Topical tacrolimus with dapsone in seven patients yielded excellent results. Early and judicious use of medicines can clear this condition without scarring. LMDF should be accepted as a distinct entity. Facial idiopathic granulomas with regressive evolution (FIGURE), an acronym suggested is an apt, self-explanatory and easy term for LMDF, with no connotation of tubercular etiology.

Classification of segmental vitiligo on the face: clues for prognosis.

BACKGROUND: The origin of the distribution of segmental vitiligo (SV) has not yet been clearly elucidated. Segmental configurations of cutaneous disorders have been explained using two main interpretations, i.e. following either dermatomal or blaschkolinear distributions. However, facial SV does not always correspond to either of these distributions. OBJECTIVES: We classified facial SV into several distinctive subtypes according to specific distributions based on long-term observations. METHODS: In total, 257 patients with facial SV were included, all of whom were closely observed for more than 1 year. The distribution patterns of facial SV were classified according to morphological similarities based on clinical observations. RESULTS: The lesions of facial SV were categorized into six subtypes: types I-a and I-b, and types II-V. Type I-a and type IV broadly involved the mid-level face from the forehead to the lower cheek, but type IV lesions selectively appeared on the right side of the face and did not cross the midline. Type I-b lesions chiefly involved the forehead and scalp hair. Types II and III involved the lower face and, frequently, the neck area, and type V lesions were distributed mostly around the right orbital area. The most frequent type of lesion in this study was type I-a (28·8%), followed by types II (16·0%), III (14·4%), IV (10·9%), I-b (10·5%) and V (8·6%). CONCLUSIONS: Newly established patterns of facial SV may be valuable for certain aspects of prognosis, such as the likely degree and path of lesion spreading.

[Feasibility and reliability of the Spanish version of the Leeds Revised Acne Grading Scale]. / Factibilidad y fiabilidad de la versión española de la escala revisada de gravedad de Leeds (LRAG) para pacientes con acné.

BACKGROUND: Although there are more than 25 acne grading systems, there is no consensus on which is most appropriate. Unification of the classifications is recommended in order to facilitate therapeutic decisions. OBJECTIVE: To assess the feasibility and reliability of the Spanish version of the Leeds revised acne grading (LRAG) scale in patients with acne vulgaris in Spain. PATIENTS AND METHODS: We conducted a prospective, multicenter, observational study in Spain, including patients with acne affecting at least 1 of 3 regions: face, back, or chest. Patients were assessed using the LRAG scale and lesion counting. Changes in the scores were determined at 4-6 weeks, and were correlated with the lesion count. Physicians were asked 4 questions regarding difficulty using the scale and the time employed. RESULTS: A total of 259 sites of acne were assessed in 239 patients at 57 centers. The majority of physicians (89.5%) stated that the LRAG scale was not difficult to use. The mean administration time was 3.12min. Cross-sectional validity (P<.012 for the face, P<.001 for the back and chest), longitudinal validity (P<.0001 for the face, back, and chest), and intraobserver and interobserver reliability (Cronbach α >0.8) were significant for inflammatory lesions in all regions. Sensitivity to change was demonstrated for lesions in all regions, based on the correlation between the difference in severity and the number of lesions recorded by the LRAG, and the difference in the lesion count between baseline and follow-up. CONCLUSION: The Spanish version of the LRAG scale is a practical and reliable tool and is sensitive to change. It is a valid tool for the objective assessment of the severity of acne.

Nonmutilating palmoplantar and periorificial kertoderma: a variant of Olmsted syndrome or a distinct entity?

BACKGROUND: Olmsted syndrome is a rare keratinization disorder characterized by mutilating palmoplantar and periorificial keratoderma as the two major diagnostic features. Some authors believe that atypical cases without this standard combination may not really belong to Olmsted syndrome. Herein, we describe two familial cases with congenital nonmutilating palmoplantar and periorificial keratoderma, and discuss their similarities and differences with Olmsted syndrome. PATIENTS: The study included two sisters who presented with focal and punctate nonmutilating palmoplantar keratoderma (PPK), periorificial hyperkeratotic plaques, and widely distributed keratotic lesions. Fragile denuded areas of the skin were found in sites exposed to trauma. Fingernails showed a characteristic form of leukonychia. RESULTS: Histopathology of plantar keratoderma showed psoriasiform hyperplasia with marked compact hyperkeratosis, while vicinity of denuded skin revealed thin parakeratotic zone and dissolution of the granular cell layer. Immunohistochemistry demonstrated suprabasal staining pattern for acidic keratin (AE1) and uniform positivity, starting four to six layers above the basal layer, for cytokeratin 10. Electron microscopy showed defective keratinization. Cytogenetic studies revealed normal karyotype and no chromosomal breakage. CONCLUSION: Our cases share Olmsted syndrome in the early onset, and the presence of symmetrical PPK, periorificial keratoderma and keratotic lesions. However, the striking nonmutilating nature of PPK and the presence of unique features in our patients suggest a newly described keratinization disorder.