Acne and Related Disorders

Acne and Related Disorders

Predictors of Severity of Acne Vulgaris in Young Adolescent Girls: Results of a Five-Year Longitudinal Study

Background.—Despite the prevalence and physical and psychological effects of acne vulgaris, little is known about the natural history of this disease. The current study determined the factors that may be useful in predicting the severity of facial acne in girls.

Methods.—Four hundred thirty-nine black and 432 white fourth- and fifth-grade girls volunteered for the study with their legal guardians’ per-mission. At annual examinations during a 5-year period, the degree of facial acne was classified as mild, moderate, or severe. In addition, blood samples were obtained at 1, 3, and 5 years.

Acne and Related DisordersFindings.—There were no racial differences in acne or hormone levels. The number of acne lesions increased progressively with age and maturation. Regardless of age, there were many more comedonal than inflammatory acne lesions. The girls with severe acne by year 5 of the study had significantly more comedones and inflammatory lesions at an earlier age than girls with mild or moderate acne. Menarche onset occurred significantly later in girls with mild comedonal acne than in those with severe comedonal acne. Compared with girls with mild or moderate comedonal acne, girls in whom severe comedonal acne developed had significantly greater serum dehydroepiandrosterone sulfate (DHEAS) levels and, in a longitudinal analysis, somewhat greater levels of testosterone and free testosterone (FT). Girls with severe comedonal acne and girls with mild or moderate comedonal acne were comparable in serum E2, testosterone/E2, progesterone, and testosterone-estrogen binding globulin (TEBG) values.

Conclusions.—Early comedonal acne appears to be one of the best predictors of later, more severe disease. The adrenal hormone DHEAS seems to have an important role in the development of acne. The persistence of severe comedonal acne is associated with DHEAS, testosterone, and FT.

This very well done study confirms some accepted data and uncovers some unsuspected facts. Open and closed comedones are the first sign of acne and may occur many years before menarche. In young girls they may be seen between the ages of 6 and 9 years. The unsuspected finding was that number of comedones at any age prior to menarche was the best predictor of future acne severity in terms of scarring and psychological damage. The implications for the clinician are important: begin treatment when comedones first appear. The authors’ discussion of the hormonal causes of acne is especially helpful. The adrenal androgen DHEAS is one of the first hormones to increase during puberty; in premenarcheal girls, DHEAS levels correlate with the presence of acne and the future severity of comedonal acne. They point out, however, that androgen measurement is warranted only when an underlying disorder such as polycystic ovarian disease or congenital adrenal hyperplasia is suspected. Factors which the authors did not consider in this study are family history and exposure to comedogenic substances.

Pathogenesis and Treatment of Acne in Childhood

Introduction.—Acne is usually observed from adolescence to adulthood but is also seen in small children, infants, and newborns. Boys are more likely to be affected than girls. Most acne lesions are confined to the face and consist of comedones, papules, and pustules. Deeper nodules and scarring are rare but can occur. Childhood acne types and treatment are described.

Acne Neonatorum.—Acne neonatorum is present at birth or develops soon thereafter. Closed comedones occur most frequently on the cheeks and forehead. Open comedones, papules, and pustules may also be observed. About 20% of newborns have acne neonatorum. Lesions usually heal spontaneously over a few weeks or months. Topical treatment with azelaic acid or mild tretinoin may be used.

Acne Infantum.—Acne infantum usually starts between 3 and 6 months of age, is more widespread and inflamed, and has a more persistent course compared with acne neonatorum. Lesions usually occur on the cheeks. These infants may experience closed and open comedones, papules, pustules, nodules, and cystic lesions that can scar. In patients with pronounced or therapy-resistant acne, one should measure free and total testosterone, dehydroepiandrosterone and its sulfate, LH, and FSH. Topical treatment is similar to that of acne vulgaris.

Acne Conglobata Infantum.—The lesions of acne conglobata infantum include deep nodules, cysts, and draining sinuses that can cause marked scarring of the face. These children usually will have severe acne as teenagers and adults. Topical and systemic therapies usually fail with these children. Use of isotretinoin may cause growth retardation because of delayed bone growth.

Acne Venenata Infantum.—Acne venenata infantum is caused by comedogenic products, such as greasy salves, creams, pomades, and oils applied by the parents. In America, it is usually seen in black children because of use of hair care products. Lesions subside when causative products are discontinued.

Steroid Acne.—Lesions of steroid acne are caused by use of topical or systemic corticosteroids. Children usually have large numbers of closely grouped inflamed papules and pustules. Topical tretinoin, isotretinoin, or benzoyl peroxide may be used if therapy is required.

Chloracne.—Aromatic hydrocarbons with chlorine groups may cause acneiform cutaneous reactions, or chloracne. Agent Orange is the best known in the United States. Skin contact, ingestion, and inhalation may cause this disorder. Chloracne is persistent and difficult to treat. Scarring may be pronounced.

Fetal Hydantoin Syndrome.—Fetal hydantoin syndrome could be caused by maternal use of diphenylhydantoin. The acne lesions are often self-limiting, but may be accompanied by retarded mental and physical development, craniofacial dysmorphism, hypoplasia of the terminal phalanxes, and dry hair.

Androluteoma Syndrome of Pregnancy.—A persistent functional corpus luteum with production of androgens during pregnancy can cause virilization in the mother. At birth, the infant may have signs of virilization, including acne. If the functioning corpus luteum is removed surgically during pregnancy, the mother and child improve spontaneously.

Conclusion.—Acne in childhood ranges from mild and transient forms to forms that may scar and are difficult to treat.

 Acne neonatorum is well recognized and occurs in up to 20% of newborns. Acne infantum begins between 3 and 6 months of age and usually persists until age 2-5. When it is severe or resistant to therapy, hormonal studies should be undertaken including free and total testosterone, dehydroepiandrosterone and its sulfate, LH, and FSH. Acne conglobata of infancy can produce marked scarring and often requires systemic retinoid therapy. The other types of acne seen in childhood are nicely reviewed and include acne venenata infantum (caused by application of greasy topical preparations), steroid acne, chloracne, fetal hydantoin syndrome, and androluteoma syndrome of pregnancy. This is an excellent review.

Treatment of Acne With a Combination Clindamycin/Benzoyl Peroxide Gel Compared With Clindamycin Gel, Benzoyl Peroxide Gel and Vehicle Gel: Combined Results of Two Double-blind Investigations

Introduction.—In the treatment of acne, an erythromycin/benzoyl peroxide combination is more effective than either agent alone. A further advantage may be possible with the combination of clindamycin/benzoyl peroxide, which does not require refrigeration after being dispensed. A clindamycin/benzoyl peroxide combination was compared with clindamycin, benzoyl peroxide, or vehicle.

Methods.—A total of 334 patients with acne were studied in 2 randomized, controlled, double-blind trials. They were assigned to 11 weeks of treatment with 5% benzoyl peroxide/1 % clindamycin, benzoyl peroxide alone, clindamycin alone, or vehicle. Each treatment was applied once nightly. During and at the end of treatment, the results were evaluated in terms of lesion counts, global responses, and irritant effects.

Results.—The 3 active treatments were all more effective than vehicle in terms of global response and inflammatory lesion counts. Clindamycin/ benzoyl peroxide was superior to each treatment alone in terms of global improvement and reduction of inflammatory lesions. The combination gel was also superior to clindamycin alone in terms of reducing noninflammatory lesions. The active treatments were as well tolerated as the vehicle gel.

Conclusions.—In the treatment of acne, the combination of clindamycin/benzoyl peroxide is more effective than either agent alone. The combination gel is well tolerated. The clindamycin/benzoyl peroxide combination can be stored without refrigeration for 2 months after dispensing.

 In the global evaluation, the clindamycin/benzoyl peroxide combination was clearly superior to either ingredient alone. However, stratification of the results showed little difference between the combination product and benzoyl peroxide alone for noninflammatory lesions; the major benefit of the combination was most apparent when treating inflammatory lesions. Obviously, an interesting follow-up study would be to compare the clindamycin/ benzoyl peroxide combination to the currently marketed erythromycin/benzoyl peroxide combination.

Negligible Systemic Absorption of Topical Isotretinoin Cream: Implications for Teratogenicity

Objective.—Topical isotretinoin is effective in repairing sun-damaged skin. Although oral retinoids are known to be teratogenic, no studies of possible teratogenic effects of topical administration of isotretinoin have been performed. The extent of systemic exposure after excessive application of 0.1% isotretinoin cream for 42 days and a comparison of such exposure against systemic concentrations of retinoic acids after a normal USRDA dose (5,000 IU) of vitamin A supplements were evaluated in a single-center, open-label, noncomparative, multiple-dose study.

Methods.—Ten grams of 0.1% isotretinoin cream were applied once daily for 42 days to skin surface of approximately 2,300 cm2 in 18 females, age 18-45. Dietary sources of vitamin A were controlled. Plasma levels of isotretinoin, tretinoin, 4-oxo-isotretinoin, and 4-oxo-tretinoin were determined at baseline and after treatment and compared by use of the area under the curve.

Results.—Plasma concentrations of 4-oxo-tretinoin were too small to be measured accurately. Concentrations of isotretinoin, 4-oxo-isotretinoin, and tretinoin increased by 47.8%, 77.3%, and 1.70% from baseline. Increases were significant for isotretinoin and for 4-oxo-isotretinoin. When healthy women took 5,000 IU of vitamin A daily for 60 days, plasma levels of isotretinoin and 4-oxo-isotretinoin increased 141% and 171% over baseline values.

Conclusion.—Systemic absorption of 0.1% isotretinoin cream is minimal and substantially smaller than plasma levels achieved with a daily vitamin A supplement of 5,000 IU.

 Numerous reports have attested to the lack of absorption of topically applied tretinoin cream and, by implication, its safety for use during pregnancy. Other reports have implied that teratogenic effects can occur, and a recent article in a prestigious medical journal claims vitamin A toxicity from topically applied tretinoin. Now the same controversy may be debated with topical isotretinoin. Despite the weight of scientific evidence, it would seem to be most judicious from a medicolegal point of view to avoid the use of these preparations during pregnancy. Good science rarely triumphs over emotion in a court of law.

Minocycline Induces an Increase in the Number of Excreting Pilosebaceous Follicles in Acne Vulgaris

Introduction.—Tetracyclines have long been used for the treatment of acne vulgaris. Several different mechanisms have been proposed to explain the efficacy of tetracyclines on the inflammatory component of acne. These drugs inhibit lipase, which reduces the amount of fatty acids in the sebum. Otherwise, how they work against the sebaceous excretion of acne vulgaris is unknown. An open and a controlled study were performed to examine the effects of minocycline—a semisynthetic cycline with a wide spectrum of lipophilic activity—in acne vulgaris.

Methods.—The 2 studies included 45 patients with moderate acne vulgaris. The controlled study was randomized and placebo controlled; the active treatment consisted of minocycline, 100 mg/day. Lipometry and Sebutape were used to assess the effects of treatment on sebaceous excretion. The measurement conditions were held stable in terms of room temperature and time of day.

Results.—During minocycline treatment, seborrhea increased along with the number of active pilosebaceous follicles. The open study documented significant increases from baseline to 2 months in seborrhea, number of blots, total surface area, and mean surface area per follicle. Thus, the increase in seborrhea resulted from an increase in the number of excreting follicles, rather than from increased excretion by existing follicles. The intensity of seborrhea was unrelated to the clinical severity of the acne. The controlled study showed a clear difference in minocyclinetreated vs. placebo-treated patients.

Conclusion.—In patients with acne vulgaris, treatment with minocycline produces a subclinical increase in seborrhea via recruitment of new excreting pilosebaceous follicles. These follicles are likely the same ones that had previously been altered and rendered nonfunctional by ductal obstruction. More study is needed to prove the relationship between increased pilosebaceous follicle excretion and elimination of ductal obstruction.

 This report suggests that minocycline treatment of acne vulgaris is associated with increased pilosebaceous gland excretion, presumably secondary to the removal of ductal obstruction. That this may explain its therapeutic effect is unlikely, given the pronounced decrease in pilosebaceous secretion routinely observed with the highly effective anti-acne drug, isotretinoin.

Comparative Safety of Tetracycline, Minocycline, and Doxycycline

Objective.—Although rare, serious adverse effects of minocycline have been reported. These events include hypersensitivity syndrome reaction (HSR), serum sickness-like reaction (SSLR), and drug-induced lupus (DIL). This retrospective study sought to determine whether similar events occur in patients taking the related antibiotics, tetracycline and doxycycline. The occurrence of serious single organ dysfunction (SOD) attributed to these drugs was studied as well.

Methods and Findings.—The study included a review of Drug Safety Clinic and Health Protection Branch data bases, as well as a literature review. Nineteen cases of HSR attributed to minocycline were identified, whereas only 2 were attributed to tetracycline and 1 to doxycycline. Cases of SSLR were attributed to minocycline in 11 cases, to tetracycline in 3, and to doxycycline in 2. There were 33 cases of DIL, all attributed to minocycline. Minocycline was responsible for 40 cases of SOD, tetracycline for 37 cases, and doxycycline for 6. The average time to development of HSR, SSLR, and SOD was 4 weeks after the start of therapy, whereas DIL occurred after an average of 2 years.

Conclusion.—Tetracycline antibiotics are linked to several different types of serious adverse events. Early events include HSR, SSLR, and SOD, whereas DIL occurs later and only with minocycline. The higher rates of adverse events with minocycline may be related to the metabolism of this drug.

 The safety of minocycline therapy for acne came into question in 1996 with reports of serious toxic effects associated with its use. It should be emphasized that whereas most of these adverse reactions occur within the first months of therapy, DIL occurs, on average. 2 years after the initiation of therapy. Patients receiving long-term treatment should be followed with liver function tests and antinuclear antibody determinations. The degree of crossreactivity between the various tetracyclines is unknown; thus, a patient who experiences a serious adverse reaction to 1 of these should avoid the others as well.

Acne, Hyperandrogenism, and Resistance to Oral Isotretinoin: 23 Casereports and Therapeutic Implications

Introduction.—In a previous report, the authors showed that the response to oral isotretinoin can be related to hyperandrogenism in female patients with acne. The reasons for failure of isotretinoin treatment in such patients were investigated.

Methods.—One hundred twenty patients who had late-onset acne that did not respond to various treatments and who had clinical signs of hyperandrogenism were studied, including being given a complete hormone workup. Twenty-three patients had failed to respond to isotretinoin; the other 97 served as controls. Patients who continued to have grade 2 lesions after a mean cumulative isotretinoin dose of 166 mg/kg were considered to be treatment failures.

Results.—All but 1 of the nonresponders to isotretinoin had laboratory evidence of hyperandrogenism. The hyperandrogenism was ovarian in 13 cases, adrenal in 5, and pituitary and peripheral in 2 cases each. Hyperandrogenism was also present in 89 of the controls and was adrenal in 45 cases, ovarian in 33, pituitary in 6, and peripheral in 5. The incidence of ovarian hyperandrogenism was significantly higher in the patients who failed to respond to isotretinoin.

Conclusion.—In women with acne, oral isotretinoin treatment may fail because of untreated hyperandrogenism, especially ovarian hyperandrogenism. To avoid repeated courses of oral isotretinoin, cyproterone acetate may be given.

 Any woman who fails to respond to oral isotretinoin therapy should be evaluated for hyperandrogenism, especially of ovarian cause. All women with severe acne should be questioned regarding signs and symptoms including menstrual irregularity, hirsutism, and voice change, all of which may indicate polycystic ovary syndrome. Appropriate laboratory tests include total and free testosterone, luteinizing hormone, and follicle stimulating hormone. A luteinizing hormone-follicle stimulating hormone ratio of more than 2 or 3 is highly suggestive of the diagnosis, which can be confirmed by ultrasound examination.

Norgestimate and Ethinyl Estradiol in the Treatment of Acne Vulgaris: A Randomized, Placebo-controlled Trial

Objective.—Because some cases of acne are linked to an excess of androgen, hormonal treatment for women with acne may be helpful. Results of a prospective phase III, 12-center, randomized, double-blind, placebo-controlled U.S. clinical trial of a triphasic oral contraceptive, norgestimate-ethinyl estradiol, for the treatment of moderate acne vulgaris in women were evaluated.

Methods.—A total of 250 women aged 15-49 years with moderate acne were randomly assigned to receive either placebo or a combination of ethinyl estradiol (0.035 mg) and norgestimate (0.180 mg for 7 days followed by 0.215 mg for days 8-14, and then 0.250 mg for days 15-21) for 6 cycles. The women used a standard skin care regimen that included use of a noncomedogenic moisturizer. Changes in inflammatory and total lesion counts and percentage of women showing improvement were recorded and analyzed along with subjective evaluations. Safety was assessed through interviews throughout the study period.

Results.—There were 179 women who completed the study. Equal numbers of women withdrew from the placebo and treatment groups. Thirteen women in the treatment group and 5 in the placebo group withdrew because of adverse events. Numbers of all types of lesions were significantly decreased in the treatment group compared to the placebo group. The difference was particularly apparent after cycle 3. Improvement was noted in 83.3% of women in the treatment group and 62.5% of women in the placebo group. No improvement was observed in 16.7% of women in the treatment group and 37.5% of women in the placebo group. The percentage of women whose response was rated excellent was 3.5 times higher in the treatment group than in the placebo group. Sex hormone-binding globulin increased by a factor of 3, percentage of free testosterone was reduced by 43%, dehydroepiandrosterone-sulfate decreased, and total testosterone was unchanged in the treatment group.

Conclusion.—This first randomized, placebo-controlled study of the effects of oral contraceptives on acne showed that the triphasic combination norgestimate-ethinyl estradiol was safe and effective for treatment of moderate acne vulgaris in women.

 Similar results have also been reported in the dermatologic literature. Although the beneficial effects of the oral contraceptive Ortho Tri-Cyclen were modest, the drug has now been approved by the Food and Drug Administration for the treatment of acne vulgaris. It would be reasonable to recommend this drug for women with acne who desire oral contraceptive therapy. When using Ortho Tri-Cyclen with oral antibiotics, one must keep in mind the possible interaction between the 2 classes of drugs.

Phototherapy of Acne Vulgaris With Visible Light

Introduction.—Sun exposure has a known beneficial effect on acne vulgaris, but it is not clear which wavelengths offer favorable effects or whether UV, visible light, or a combination are needed to achieve benefits. Even though UVB has the potential to destroy Propionibacterium acnes in vitro, it is probably not clinically important as its capacity to penetrate skin is low. The effect of visible light on acne may be caused by a decrease of P. acnes in acne lesions. Bacterial resistance to antibiotics is one reason for needing new therapeutic approaches. The effect on acne vulgaris of visible light and its most effective wavelengths was evaluated.

Methods.—Fifteen males and 15 females with mild to moderate acne involving the face or back or chest underwent irradiation with 1 of 3 light sources: full spectrum light, violet light, and green light. Patients underwent treatment for 20 minutes 3 times weekly for 7 weeks.

Results.—Of 45 fields treated 20 times, 15,16, and 14 were treated with violet light, green light, and full spectrum light, respectively. All 3 light sources caused improvement of acne: full spectrum light 14%, green light 22%, and violet light 30%. There were no significant between-group differences in treatment effect, but violet light had a tendency to be better than the other light sources. There were no side effects. The main effect of phototherapy was on pustules and infiltrates. Comedones and papules were only slightly affected.

Conclusion.—Phototherapy offered a significant, but modest decrease in acne severity, even when only visible light was used. Seven patients chose to withdraw after 12 treatment sessions, primarily because they were not satisfied with their results. The objective decrease in the acne score was comparable in patients who withdrew to the decrease in those who completed the trial.

 The small population, the brief duration of the study, and the lack of controls compromise the validity of the results. The authors suggest that visible light may have an effect on Propionibacterium acnes, yet no attempt was made to correlate a decrease in bacterial count with clinical improvement. In addition, many of the patients who discontinued their participation in the study did so because they were not satisfied with their response to therapy, yet the objective reduction in acne in these patients was comparable to that in those “satisfied” patients who completed the study. In summary, the modest benefit of visible light therapy reported by these authors does little to change current treatment recommendations for acne vulgaris.

The Effectiveness of Acne Treatment: An Assessment by Patients of the Outcome of Therapy

Objective.—Kent can have a major impact on quality of life (QOL). Studies can show the effects of treatment on the clinical features of acne, but there are few data on the benefits of treatment from the patient’s perspective. Patient-assessed QOL was measured before and after treatment for acne, and compared with clinical assessments of disease severity.

Methods.—A total of 90 patients referred to a dermatology clinic for treatment of acne were studied. Before consultation and 4 and 12 months afterwards, the patients completed various QOL assessments: the Short Form 36 instrument (SF-36), the Dermatology Life Quality Index (DLQI), Rosenberg’s measure of self-esteem, and the General Health Questionnaire (GHQ-28). A dermatologist performed clinical assessments at baseline and at 4 months. All patients received standard treatments for acne.

Results.—At least 1 follow-up questionnaire was complete by 89% of patients. Treatment produced significant improvements in the clinical grade of acne. In addition, the follow-up questionnaires showed significant improvements on the DLQI, the self-esteem measure, the GHQ-28, and the 5 dimensions of the SF-36 that were impaired at baseline (roleemotional, social function, mental health, energy/vitality, and pain). From 4 to 12 months, there were continued improvements in QOL. Patients receiving isotretinoin showed better clinical and QOL outcomes than those receiving other treatments.

Conclusions.—Effective treatment for acne can significantly reverse the disability caused by this skin disease. Patient assessments of QOL and other outcomes respond to changes in disease severity over time, and are correlated with differences in treatment effectiveness. The findings suggest that isotretinoin offers better patient-assessed outcomes than other treatments, which could contribute to the debate regarding the cost-effectiveness of isotretinoin.

 Patient-assessed outcomes are becoming increasingly important in clinical research studies. Especially in the current managed care climate, where budgetary matters increasingly influence clinical decisions, it is important to have a way of measuring patients’ views of the benefits of specific therapies. This may be especially important in situations such as treatment with isotretinoin, where a specific drug is significantly more effective, but also significantly more expensive, than alternative therapies.

Sebum Excretion in Hidradenitis Suppurativa

Background.—Hidradenitis suppurativa and acne are similar, in that histologic findings, follicular occlusion, and signs of androgenicity are comparable in both. However, the 2 diseases do differ in their epidemiology and susceptibility to certain drugs. Other factors must be in part responsible for the different pathogeneses of these 2 diseases. One pathogenic factor that is very prominent in acne—sebum excretion—has not been studied in hidradenitis suppurativa, and these authors set out to do just this.

Methods.—All participants were women between 20 and 52 years of age. Patients with hidradenitis suppurativa (n =16) and healthy women (n = 16) were examined during the last 2 weeks of their menstrual cycle. Each participant was washed and shaved on the cheeks, axillae, and genitofemoral folds in preparation for the placement of Sebutape®, which was left in place for 1 hour. Sebutapes were examined under a fiberoptic microscope with subsequent image analysis to determine the total number, density, width, height, perimeter, and compactness of sebum excretion spots. A blinded investigator rated signs of androgen excess in each participant, including androgenic alopecia, hirsutism, hidradenitis, and acne vulgaris.

Findings.—Patients and controls did not differ significantly in the parameters of sebum excretion measured on the Sebutape. Both patients and controls had a significantly greater spot size and significantly more active sebum-excreting glands on the face than in the axilla or the groin. Furthermore, clinical markers of androgen excess did not differ between the 2 groups.

Conclusions.—Patients with hidradenitis suppurativa do not differ from controls in the amount of or characteristics of sebum excretion or in clinical markers of androgenicity. Furthermore, regional sebaceous activity patterns are similar in patients and controls. Thus, the sebaceous glands do not seem to play a role in hidradenitis suppurativa, which helps explain why these patients do not respond to drugs like isotretinoin.

 These results suggest that sebum excretion is not an important factor in the development of hidradenitis. Although the authors claim that this may explain the “generally unsatisfactory therapeutic effect of retinoids” in this disorder, I personally have found them to be quite valuable drugs, although they must be used in higher doses and for longer periods than are recommended for treating acne.

Ocular Rosacea: Patient Characteristics and Follow-up

Purpose.—The reported incidence of ocular involvement in rosacea varies widely, from 3% to 58%. The ocular findings can range from mild blepharoconjunctivitis to vision-threatening corneal involvement, even perforation. A series of 131 patients with ocular rosacea was reviewed, including the demographic characteristics, presenting signs and symptoms, treatment, complications, and outcomes.

Patients.—The patients were 131 women and 75 men (mean age, 56 years) and all were white. For most patients, the chief complaint was a foreign body sensation, pain, burning, or redness. Usually, both eyes were affected at once. Decreased visual acuity resulting from corneal complications was sometimes the chief complaint. Reasons for referral included cicatrizing conjunctivitis in 12 patients, treatment of ocular rosacea in 5, recurrent chalazia in 2, and recurrent episcleritis in 1. Eighty-five percent of patients had facial rosacea at their initial visit, but it was usually not severe. Just 12 patients had a previous diagnosis of acne rosacea. Skin manifestations developed later in 11 patients, and an additional 8 had only mild skin changes during a mean follow-up of 13 months. The ocular involvement affected mainly the eyelids, conjunctiva, and cornea. Eighty-one percent of patients had telangiectasia and irregular lid margins.

Treatment and Outcomes.—Eighty-six percent of patients were treated with oral tetracycline derivatives. Tetracycline was generally started at a dose of 250 mg 4 times a day, or 100 mg doxycydine was taken once daily. Antibiotics were tapered and discontinued after ocular rosacea had been in remission for 3-6 months; low-dose maintenance therapy was continued indefinitely for patients with sight-threatening complications. Two patients did not respond to either drug; the rest showed dramatic improvement within 2-6 weeks. The rate of adverse effects was 25%, of which nausea and photosensitivity were the most common. Of the 7 patients with advanced cicatrizing conjunctivitis, all remained in stable condition while receiving oral tetracycline, and there were no further complications. The follow-up was at least 3 years in 47 patients. Six of these were left with a visual acuity of 20/400 or worse, which was the result of opaque corneal grafts.

Conclusions.—Ocular rosacea is a common condition that, although usually relatively mild, can be sight-threatening. There is no specific test or specific findings for ocular rosacea. Because the skin lesions may be mild, ocular rosacea is underdiagnosed by ophthalmologists. Although complicated and prolonged, treatment gives good results.

 In this series, of the 131 patients with ocular rosacea, facial involvement was present in 112. The strong association between skin disease and eye disease most certainly represents a selection bias, as patients referred to an ophthalmology clinic would be expected to have a very high incidence of ocular complaints. Most dermatologic texts report the incidence of ocular involvement in patients with facial rosacea to be significantly less than that reported in this study.

Ocular Rosacea: Signs, Symptoms, and Tear Studies Before and After Treatment With Doxycycline

Purpose.—As many as 58% of patients with rosacea may have ocular involvement. When ophthalmologists see these patients, they usually diagnose some type of inflammatory eye disease, such as blepharitis or conjunctivitis. A detailed clinical study of ocular involvement with rosacea was reported, including the findings after doxycycline therapy.

Methods.—The study included 39 consecutive patients with cutaneous rosacea: 29 women and 10 men. All were treated with doxycycline, 100 mg/day, for 12 weeks. At the beginning of the study and after 4, 8, and 12 weeks of treatment, the patients had a thorough dermatologic and ocular evaluation. They also underwent measurement of tear break-up time (TBUT) and a Schirmer test to measure aqueous tear production. Thirty-three patients completed the study.

Results.—Dermatologic disease stage was stage I in 4 patients, stage II in 24 patients, and stage III in 5 patients. Treatment had little impact on cutaneous disease stage during the 12-week observation period, although the number of primary and secondary lesions was markedly improved. Eighty-five percent of patients had ocular symptoms, most commonly dryness, itching, blurred vision, and photosensitivity. All of these symptoms had significantly improved by the end of the study. All patients had objective signs of ocular involvement, most commonly telangiectases, erythema, and meibomian gland dysfunction. During treatment, they experienced significant reductions in scales, erythema and telangiectasia, ciliary base injection, bulbar injection, papillary hypertrophy, and punctate epithelial erosions. Mean TBUT improved from 5.7 seconds at baseline to 10.8 seconds after 12 weeks. Patients with more ocular signs had a lower TBUT.

Conclusion.—Most patients with cutaneous rosacea will have ocular involvement to some extent. The dermatologist should ask about ocular symptoms, examine the eyelids, and consider ophthalmologic examination. Treatment should consider not only the skin but also the eyes; this is an especially important consideration for patients with initially mild cutaneous rosacea, who are likely to be given topical medication only. A short course of doxycycline may be a useful adjunctive therapy for patients with ocular rosacea.

 Remarkably, all patients with cutaneous rosacea in this study had signs of ocular involvement. Indicators of ocular rosacea include ocular erythema and telangiectasia, meibomian gland dysfunction, and short TBUT. Doxycydine, 100 mg daily, appears to be an effective treatment.

Perioral Dermatitis in Children: Clinical Presentation, Pathogenesisrelated Factors and Response to Topical Metronidazole

Introduction.—Although perioral rosacea-like dermatitis occurs often in young women, this skin disorder is rarely reported in children. The 7 children described here were carefully examined for possible etiologic factors associated with their perioral dermatitis.

Patients and Findings.—Patients were 4 girls and 3 boys who ranged in age from 4 to 12 years. Five children had additional lesions in perinasal and/or periocular sites. Duration of symptoms before evaluation ranged from 2 to 7 months. All but 1 child had been pretreated with moderate to strong-potency topical corticosteroids, and some had received antibiotics as well. Results of skin prick tests using a panel of 6 common aeroallergens were negative in 6 children and without clinical relevance in 1. Treatment consisted of topical 1 % metronidazole applied once daily for the first week and twice a day during the second week; from week 3 until resolution of skin lesions, 2% metronidazole was applied twice daily. Three to 6 months were required for complete resolution of the lesions. All children have remained clear of symptoms over a follow-up of 2 years.

Discussion.—The first step in the therapeutic management of perioral dermatitis in children should be the discontinuation of all topical steroids, which may play a pathogenic role. Neither atopy nor gastrointestinal colonization with Candida albicans appears to be involved in the pathogenesis of the skin disorder. Metronidazole proved to be a safe and effective treatment for children with perioral dermatitis.

 Perioral dermatitis is being diagnosed more frequently in children. It most often presents with perioral, perinasal, and periocular papules in a characteristic distribution with sparing of the skin around the vermillion border. The authors found no association between Candida albicans colonization and perioral dermatitis. Because most children tested had negative prick test results, the authors concluded that atopy is not associated with perioral dermatitis. Certainly, additional criteria for atopy should be tested before an association can be proved or disproved. Investigation for Demodex mites would be interesting. The authors confirm that previous topical steroid treatment is frequently associated with perioral dermatitis and that resolution with metronidazole treatment may require 3-6 months, In children, treatment options other than topical metronidazole include topical tetracycline or erythromycin, or systemic erythromycin.

Demodicidosis in Immunocompetent Young Children: Report of Eight Cases

Introduction.—Demodex folliculorum and Demodex brevis, the most common permanent ectoparasites in adults, are rarely found on the skin of young children. Most cases of demodicidosis reported in children younger than 5 years of age have been associated with leukemia or HIV infection. The 8 cases described here all involved young immunocompetent children.

Patients and Findings.—The 8 children, 4 boys and 4 girls, ranged in age from 10 months to 5 years; 6 were 14 months of age or younger. The duration of disease before evaluation of the facial eruption ranged from 1 week to 4 years (7 were seen within 5 months or less of onset). The lesions consisted of papules or papulopustules associated with erythema and variable edema. In most patients, the dorsum of the nose was affected. Inflammation was mild in 2 cases and more prominent in 6. No subjective symptoms were reported. Diagnosis was confirmed by the finding of numerous D. folliculorum mites in skin scrapings in 7 patients and by histologic examination of a skin biopsy specimen in 1. Lesions cleared completely after 3-4 weeks of treatment with 1% metronidazole gel twice daily. With follow-up ranging from 12 to 38 months, there have been no recurrences.

Discussion.—Demodicidosis in these young immunocompetent children did not respond to any previous treatment, but 1% metronidazole gel yielded a cure rate of 100%. A facial rash associated with papules, pustules, and variable edema and localized on the nose and cheeks should suggest the diagnosis. The diagnosis can be confirmed by a skin scraping to investigate the presence of D. folliculorum.

 Demodex dermatitis or demodicidosis has been reported in immunosuppressed young children undergoing chemotherapy for leukemia or having HIV infection. This is the first report of a rosacea-like dermatitis occurring in immunocompetent young children. Children with an erythematous papular or pustular eruption over the nose, malar areas, and chin should undergo skin scraping examination for Demodex mites as well as dermatophytes. Because Demodex mites are usually not found on potassium hydroxide examination of the face, their presence in young children is presumed to represent causality. The treatment of Demodex dermatitis recommended by these authors is topical metronidazole for 3-4 weeks. An alternative therapy that has worked well for other authors is permethrin 5% cream twice a day for 1 week.

Demodex-associated Folliculitis

Background.—Demodex mites are extremely common, and some researchers consider their presence in the typical biopsy specimen to be incidental. However, other researchers believe these mites to be associated with clinical disease. The association between Demodex mites and the presence of histologic folliculitis was examined to determine if Demodex mites are more common in such follicles.

Methods.—Skin specimens of breast cancer, basal cell carcinoma, or melanoma were examined for the presence of Demodex mites. Areas uninvolved by surgery were examined, and at least 1 mite had to be seen for the sample to be included. Follicles with mild to moderate inflammation (follicular spongiosis, mild lymphocytic infiltrate of follicular epithelium, or perifollicular lymphocytic or plasmacytic infiltrate) were included.

Findings.—Of the 388 follicles examined, 208 (54%) were inflamed and .180 (46%) were not. Of the 208 follicles with inflammation, 87 (42%) also had Demodex mites present. Of the 180 follicles without inflammation, only 18 (10%) had Demodex mites. Looked at another way, of the 105 follicles in which Demodex mites were found, 87 (83%) also had folliculitis. These differences were statistically significant.

Conclusions.—There is a strong association between folliculitis and the presence of the Demodex mite. These data do not confirm that this is a causal relationship, although other investigators have suggested such an association.

 These results do not prove that Demodex causes folliculitis; the organism may simply enjoy residing in inflamed follicles, which leak fluids rich in fat and protein and provide better nourishment. Demodex mites are most frequently found in areas with the most sebaceous glands, and the greater numbers observed in patients with rosacea may be secondary to the sebaceous hyperplasia characteristic of that disorder. An argument supporting the pathogenic role of Demodex is the therapeutic usefulness of topical metronidazole in treating rosacea.

 Ah, the pesky mite! The debate over the association of Demodex with folliculitis rages on. In this study, Dr. Vollmer examined 388 follicles incidentally seen in 24 large skin specimens obtained for different reasons, including excision of skin cancers. More than half the follicles had histologic evidence of inflammation and, among these, 42% contained Demodex mites within the plane of the slide. Ninety percent of follicles without inflammation had no associated Demodex. Accordingly, the author concluded that Demodex mites and follicular inflammation are preferentially associated. Unfortunately, this study, while interesting, does not help clarify the issue regarding the role of Demodex in disease processes such as rosacea.

Trichostasis Spinulosa: A Clinical Simulant of Acne Open Comedones

Objective.—Trichostasis spinulosa (TS) results from retention of multiple vellus hairs within pilosebaceous follicles. Because a blackhead-like plug is produced, the condition is frequently misdiagnosed as acne. Most commonly found in the middle-aged and elderly, TS is not well covered in the pediatric literature. A case of TS in a teenager, where it was mistaken for open comedones, is presented.

Case Report.—A black girl, 13, well nourished, had “acne blackheads” on her nose since age 18 months that had been treated unsuccessfully with benzoyl peroxide. Under a magnifying glass, black, spinelike projections were seen protruding from the lesions.

Discussion.—Trichostasis spinulosa is common, may occur at all ages, and is typically found on the head and face. Its characteristic comedo-like lesions contain tufts of short, spiny vellus hairs embedded in a keratinaceous plug. Although there is no established treatment for TS, use of depilatory waxes or 0.05% topical tretinoin solution once a day has shown some success. Use of systemic tretinoids has not been reported. Keratolytics have not proven useful but may be helpful after depilatories.

Conclusion.—Trichostasis spinulosa may occur at any age and is characterized by comedo-like lesions containing tufts of short, spiny vellus hairs embedded in a keratinaceous plug. The condition must be distinguished from acne vulgaris, and treatment must be individualized.

 Although trichostasis spinulosa is often confused with open comedones, the two conditions must be differentiated because they are distinct entities with different prognoses and, with the exception of topical retinoids, different treatments.