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Potential influence of bacterial biofilm formation on scalp folliculitis therapy
2773
3275
Potential influence of bacterial biofilm formation on scalp folliculitis therapy Simone Ramos Nogueira Guerra Neri, Instituto Butantan, S~ao Paulo, Brazil; Rosely Alves, Instituto Butantan, S~ao Paulo, Brazil; Marcia Regina Franzolin, Instituo Butatan, S~ao Paulo, Brazil; Vaniky Duarte Marques, Instituto Butantan, Brazil; Thiago Jord~ao da Silva Lemos, Instituto Butantan, S~ao Paulo, Brazil; Irys Viana Neves, Instituto Butantan, S~ao Paulo, Brazil; Camila Bueno Pacheco Pereira, Instituto Butatan, S~ao Paulo, Brazil; Marta de Oliveira Domingos, Instituto Butantan, S~ao Paulo, Brazil; Luiz Carlos Cuce, PhD, Universidade de Santo Amaro, S~ao Paulo, Brazil; Durvanei Augusto Maria, PhD, Instituto Butantan, S~ao Paulo, Brazil
Progression of hidradenitis suppurativa: Outcomes of placebo-treated patients in a phase 3, randomized, placebo-controlled trial (PIONEER II) Alexander Boer Kimball, Massachusetts General Hospital, Boston, MA, United States; Gregor B. E. Jemec, Roskilde Hospital, University of Copenhagen, Copenhagen, Denmark; David M. Brooks, AbbVie Inc, North Chicago, IL, United States; Yihua Gu, AbbVie Inc, North Chicago, IL, United States; Henrique D. Teixeira, AbbVie Inc, North Chicago, IL, United States Introduction: Hidradenitis suppurativa (HS) is a chronic, painful skin disorder characterized by inflammatory skin lesions. This prespecified analysis evaluated progression of untreated HS among patients (pts) receiving placebo (PBO) continuously during a 36-week clinical trial. Methods: PIONEER II was a phase 3, multicenter, randomized, double-blind trial that enrolled adults with at least 1-year history of moderate-to-severe HS. Pts were randomized to adalimumab (ADA) 40 mg weekly or PBO for 12 weeks, and ADA pts were rerandomized to ADA weekly, ADA every other week, or PBO, while PBO pts received PBO, from weeks 12 up to 36. Use of a concomitant stable dose of doxycycline or minocycline was permitted. Primary efficacy endpoint was proportion of pts who achieved HS clinical response (HiSCR; $50% reduction in inflammatory lesion count (total abscesses and inflammatory nodules [AN] counts) with no increase in abscess/draining fistulas counts relative to baseline [BL]) at 12 weeks. Pts who achieved HiSCR at week 12 and experienced a loss of response (LOR; loss of 50% of improvement from BL to week 12) after week 12 and pts who failed to achieve HiSCR at week 12 and experienced worsening or absence of improvement (WOAI; AN count $ AN count at BL on 2 consecutive visits) after week 16 were discontinued from study and could enter an open-label extension study to receive ADA 40 mg weekly. This prespecified analysis reports the rates of LOR and WOAI.
Scalp folliculitis is considered to be an inflammatory reaction of the hair follicle, whose cause has not been elucidated. Several studies have demonstrated, however, that bacteria, yeasts and mites are all associated with this disease, although, in severe cases S aureus seems to be predominant. The treatment of folliculitis can be performed by the use of topical or oral antibiotics such as tetracycline, with the latter being used usually in cases of long term infections. There is a general consensus that increase in time taken to treat severe infections is associated with bacterial biofilm formation, since one characteristic of the biofilm is to decrease the pathogen susceptibility to antibiotics. Based on the premise that bacterial biofilm can influence the outcome of infections, we investigated whether biofilm-forming bacteria could be associated with scalp folliculitis. Accordingly, biopsies of the hair follicle of eight patients with scalp folliculitis were teased apart in PBS and incubated aerobically at 378C for 24 hours in in both TSB medium and TSA plates. Subsequently, the isolates were spread in TSA and the colonies were identified by API Staph (BioMerieux). To determine the level of bacterial proliferation, four microliters of each isolate, previously grown in TSB overnight at 378C, were added in triplicate to 96 well culture plates containing TSB at different pHs, or TSB diluted in the culture supernatant of S aureus or S lugdunensis (200 l/well). The plate was then incubated at 378C for 18h and proliferation was determined by reading the plate at 595 nm on a Multiskan EX plate reader. In order to measure the biofilm production, the same plate used for proliferation was subsequently washed with PBS, fixed with 75% ethanol and the remaining bacteria contained therein were stained with crystal violet solution. The crystal violet retained was solubilized with 95% ethanol and the optical density read at 595nm. The results showed the presence of S aureus, S lugdunensis, S epidermidis, S warneri, and a mixture of S aureus and S lugdunensis in two samples. All the isolates were able to produce biofilm and were resistant to erythromycin (81.8%). They were also able to proliferate and form biofilm at different pHs. It was also observed that S aureus can decrease the biofilm of S lugdunensis in mixed cultures. In contrast, the presence of S lugdunensis seems to increase the proliferation and the biofilm production of S aureus. In summary, the data obtained in this study suggest that opportunistic biofilmforming bacteria such as S lugdunensis and S epidermidis can contribute to the development of scalp folliculitis. Also, biofilm formation and resistance to the antibiotics that are most commonly used in therapy can be involved in the prolongation of the disease. Finally, the presence of mixed infections with S lugdunensis and S aureus can worsen the prognosis.
Results: Discontinuation rates for pts randomized to weekly ADA were 4.9% (8/163) at 12 weeks and 45.1% (23/51) at 36 weeks, and for PBO 7.36% (12/163) at Week 12 and 73.5% (111/151) at Week 36. Most frequently reported reason for discontinuation was LOR or WOAI. At week 12, 27.6% (45/163) of pts in PBO group achieved HiSCR. This rate decreased to 15.9% (24/151) at week 36. 32 pts randomized to PBO continued BL antibiotics in first 12 weeks, of which 7 (21.9%) achieved HiSCR. AN counts increased for a substantial proportion of PBO-treated pts during weeks 12 to 36; subsequently, rates of LOR and WOAI increased with each visit after week 12 to 12.6% and 43.0%, respectively, at week 36. Conclusion: Pts who received PBO during this 36-week study experienced progression of HS, as indicated by increased AN counts and high rates of LOR and WOAI. Without early study discontinuation and receiving active treatment, further progression may have been reported. AbbVie Inc participated in the study design; study research; collection, analysis and interpretation of data; and writing, reviewing and approving of this publication. All authors had access to the data, and participated in the development and review.
Commercial support: None identified.
2839 Primary follicular mucinosis: Case report Ana Carolina Folchini de Barcelos, MD, Universidade do Sul de Santa Catarina, Tubar~ao - SC, Brazil; Laura Loures Tavares, MD, Hospital Naval Marcılio Dias, Rio de Janeiro, Brazil; Caroline Ferreira de Moraes, MD, Irmandade Santa Casa de Miseric ordia de Porto Alegre, Porto Alegre, Brazil; Dalva Fabris Pasini Rodrigues, MD, Hospital Naval Marcılio Dias, Rio de Janeiro, Brazil; Glaucia Pereira Christo Antonioli, MD, Centro Universitario Lusıada, Santos - SP, Brazil; Thuany Silva Santos, MD, Hospital Naval Marcılio Dias, Rio de Janeiro, Brazil Follicular mucinosis is a relatively rare inflammatory disease, characterized by the accumulation of mucin and lymphocytes in the infundibular portion of the pilosebaceous unit, promoting total and irreversible destruction of the affected area. It can be classified as primary, benign and self-limited, with few lesions restricted to the cephalic extremity of children or young adults; prolonged primary form, more common in older individuals, with more generalized lesions in the extremities, face and trunk, and a course many times superior to two years; and in the secondary form associated to other processes, especially mycosis fungoidesetype cutaneous T-cell lymphoma. Histopathology is essential in the diagnosis, and is characterized by mucinous degeneration in the external sheath of the hair follicle and sebaceous gland, in addition to inflammatory infiltrate of lymphocytes, macrophages and eosinophils. Despite the possibility of spontaneous regression in the idiopathic forms, one must take into account the use of topical, intralesional or systemic, dapsone, indomethacin, interferons, minocycline corticosteroids and PUVA for the treatment. The treatment of secondary form should be the treatment of the associated disease. We report a case of a male patient, 7 years of age, with development of a few months of single, rounded, erythematous, slightly scaly plaque in the supraciliar region, asymptomatic, with partial alopecia of the right eyebrow. The histopathologic examination revealed perivascular lymphocytic infiltrate without atypia and with scattered intermingled eosinophils. Mucinous degeneration and dilation of the pilosebaceous follicle were demonstrated by staining with Alcian-blue. The patient was diagnosed with primary follicular mucinosis by means of clinical, pathological and immunohistochemical data, and was isolated in this first moment from association with another pathology. The topical treatment was performed with mometasone cream 1 mg/g twice a day for 30 days, observing the significant regression of the lesion. The patient was instructed to undergo annual clinical monitoring and keep an eye on the appearance of new lesions. The knowledge of the uncommon disease and little seen in doctors’ practices, assists in the differential diagnosis of atypical cutaneous lesions that may be confirmed with the histopathologic diagnosis. Commercial support: None identified.
AB68
J AM ACAD DERMATOL
3300 Prospective study of cutaneous adverse effects associated with BRAF inhibitor dabrafenib and MEK inhibitor trametinib: A study of 12 patients Jean-Philip Lacroix, MD, McGill University, Montreal, Quebec, Canada; Beatrice Wang, MD, McGill University, Royal-Victoria Hospital, Montreal, Quebec, Canada; Catalin Mihalciouiu, MD, McGill University, Royal-Victoria Hospital, Montreal, Quebec, Canada Background: Dabrafenib, a novel selective small molecule inhibitor of BRAF, has been shown to increase progression-free survival and overall survival in patients with unresectable metastatic melanoma harboring the BRAFV600E mutation. The development of resistance has led to the combination therapy with selective MEK inhibitor trametinib. These novel small molecule inhibitors are associated with adverse cutaneous side effects. Compared to vemurafenib, dabrafenib is a more recent BRAF inhibitor FDA approved in May 2013 for metastatic melanoma; less data is available in the current literature regarding cutaneous toxicity, mainly because of its more recent use. Objective: We sought to present additional cutaneous side effects of dabrafenib and trametinib, follow their evolution and management. Methods: We carried out a prospective study of 12 patients treated with dabrafenib alone or in combination with trametinib. Patients were followed every 4 weeks and we collected detailed dermatologic symptoms, photos and biopsy specimens, which enabled us to classify the cutaneous side effects. Results: All patients presented with at least one adverse skin reaction. The mean duration of treatment was 24 weeks. The most common adverse effect was verrucous keratosis (6/12), followed by palmoplantar hyperkeratosis (5/12) and alopecia (4/12). Two patients developed a seborrheic dermatitis-like eruption of the face. Two patients who received dabrafenib and trametinib developed an acneiform eruption (2/3). One patient developed a keratoacanthoma-like squamous cell carcinoma. We report no photosensitivity and no morbilliform eruptions in our cohort. Side effects presented as early as 2 weeks after starting therapy, with a mean time of onset of 8.1 weeks. Conclusion: Selective BRAF inhibitor dabrafenib and MEK inhibitor trametinib are associated with multiple skin adverse effects that have an impact on patient’s quality of life. Given their recent approval and the potential for malignant lesions to develop on treatment, awareness of potential adverse effects and their management is necessary. Commercial support: None identified.
MAY 2016
3275
Potential influence of bacterial biofilm formation on scalp folliculitis therapy Simone Ramos Nogueira Guerra Neri, Instituto Butantan, S~ao Paulo, Brazil; Rosely Alves, Instituto Butantan, S~ao Paulo, Brazil; Marcia Regina Franzolin, Instituo Butatan, S~ao Paulo, Brazil; Vaniky Duarte Marques, Instituto Butantan, Brazil; Thiago Jord~ao da Silva Lemos, Instituto Butantan, S~ao Paulo, Brazil; Irys Viana Neves, Instituto Butantan, S~ao Paulo, Brazil; Camila Bueno Pacheco Pereira, Instituto Butatan, S~ao Paulo, Brazil; Marta de Oliveira Domingos, Instituto Butantan, S~ao Paulo, Brazil; Luiz Carlos Cuce, PhD, Universidade de Santo Amaro, S~ao Paulo, Brazil; Durvanei Augusto Maria, PhD, Instituto Butantan, S~ao Paulo, Brazil
Progression of hidradenitis suppurativa: Outcomes of placebo-treated patients in a phase 3, randomized, placebo-controlled trial (PIONEER II) Alexander Boer Kimball, Massachusetts General Hospital, Boston, MA, United States; Gregor B. E. Jemec, Roskilde Hospital, University of Copenhagen, Copenhagen, Denmark; David M. Brooks, AbbVie Inc, North Chicago, IL, United States; Yihua Gu, AbbVie Inc, North Chicago, IL, United States; Henrique D. Teixeira, AbbVie Inc, North Chicago, IL, United States Introduction: Hidradenitis suppurativa (HS) is a chronic, painful skin disorder characterized by inflammatory skin lesions. This prespecified analysis evaluated progression of untreated HS among patients (pts) receiving placebo (PBO) continuously during a 36-week clinical trial. Methods: PIONEER II was a phase 3, multicenter, randomized, double-blind trial that enrolled adults with at least 1-year history of moderate-to-severe HS. Pts were randomized to adalimumab (ADA) 40 mg weekly or PBO for 12 weeks, and ADA pts were rerandomized to ADA weekly, ADA every other week, or PBO, while PBO pts received PBO, from weeks 12 up to 36. Use of a concomitant stable dose of doxycycline or minocycline was permitted. Primary efficacy endpoint was proportion of pts who achieved HS clinical response (HiSCR; $50% reduction in inflammatory lesion count (total abscesses and inflammatory nodules [AN] counts) with no increase in abscess/draining fistulas counts relative to baseline [BL]) at 12 weeks. Pts who achieved HiSCR at week 12 and experienced a loss of response (LOR; loss of 50% of improvement from BL to week 12) after week 12 and pts who failed to achieve HiSCR at week 12 and experienced worsening or absence of improvement (WOAI; AN count $ AN count at BL on 2 consecutive visits) after week 16 were discontinued from study and could enter an open-label extension study to receive ADA 40 mg weekly. This prespecified analysis reports the rates of LOR and WOAI.
Scalp folliculitis is considered to be an inflammatory reaction of the hair follicle, whose cause has not been elucidated. Several studies have demonstrated, however, that bacteria, yeasts and mites are all associated with this disease, although, in severe cases S aureus seems to be predominant. The treatment of folliculitis can be performed by the use of topical or oral antibiotics such as tetracycline, with the latter being used usually in cases of long term infections. There is a general consensus that increase in time taken to treat severe infections is associated with bacterial biofilm formation, since one characteristic of the biofilm is to decrease the pathogen susceptibility to antibiotics. Based on the premise that bacterial biofilm can influence the outcome of infections, we investigated whether biofilm-forming bacteria could be associated with scalp folliculitis. Accordingly, biopsies of the hair follicle of eight patients with scalp folliculitis were teased apart in PBS and incubated aerobically at 378C for 24 hours in in both TSB medium and TSA plates. Subsequently, the isolates were spread in TSA and the colonies were identified by API Staph (BioMerieux). To determine the level of bacterial proliferation, four microliters of each isolate, previously grown in TSB overnight at 378C, were added in triplicate to 96 well culture plates containing TSB at different pHs, or TSB diluted in the culture supernatant of S aureus or S lugdunensis (200 l/well). The plate was then incubated at 378C for 18h and proliferation was determined by reading the plate at 595 nm on a Multiskan EX plate reader. In order to measure the biofilm production, the same plate used for proliferation was subsequently washed with PBS, fixed with 75% ethanol and the remaining bacteria contained therein were stained with crystal violet solution. The crystal violet retained was solubilized with 95% ethanol and the optical density read at 595nm. The results showed the presence of S aureus, S lugdunensis, S epidermidis, S warneri, and a mixture of S aureus and S lugdunensis in two samples. All the isolates were able to produce biofilm and were resistant to erythromycin (81.8%). They were also able to proliferate and form biofilm at different pHs. It was also observed that S aureus can decrease the biofilm of S lugdunensis in mixed cultures. In contrast, the presence of S lugdunensis seems to increase the proliferation and the biofilm production of S aureus. In summary, the data obtained in this study suggest that opportunistic biofilmforming bacteria such as S lugdunensis and S epidermidis can contribute to the development of scalp folliculitis. Also, biofilm formation and resistance to the antibiotics that are most commonly used in therapy can be involved in the prolongation of the disease. Finally, the presence of mixed infections with S lugdunensis and S aureus can worsen the prognosis.
Results: Discontinuation rates for pts randomized to weekly ADA were 4.9% (8/163) at 12 weeks and 45.1% (23/51) at 36 weeks, and for PBO 7.36% (12/163) at Week 12 and 73.5% (111/151) at Week 36. Most frequently reported reason for discontinuation was LOR or WOAI. At week 12, 27.6% (45/163) of pts in PBO group achieved HiSCR. This rate decreased to 15.9% (24/151) at week 36. 32 pts randomized to PBO continued BL antibiotics in first 12 weeks, of which 7 (21.9%) achieved HiSCR. AN counts increased for a substantial proportion of PBO-treated pts during weeks 12 to 36; subsequently, rates of LOR and WOAI increased with each visit after week 12 to 12.6% and 43.0%, respectively, at week 36. Conclusion: Pts who received PBO during this 36-week study experienced progression of HS, as indicated by increased AN counts and high rates of LOR and WOAI. Without early study discontinuation and receiving active treatment, further progression may have been reported. AbbVie Inc participated in the study design; study research; collection, analysis and interpretation of data; and writing, reviewing and approving of this publication. All authors had access to the data, and participated in the development and review.
Commercial support: None identified.
2839 Primary follicular mucinosis: Case report Ana Carolina Folchini de Barcelos, MD, Universidade do Sul de Santa Catarina, Tubar~ao - SC, Brazil; Laura Loures Tavares, MD, Hospital Naval Marcılio Dias, Rio de Janeiro, Brazil; Caroline Ferreira de Moraes, MD, Irmandade Santa Casa de Miseric ordia de Porto Alegre, Porto Alegre, Brazil; Dalva Fabris Pasini Rodrigues, MD, Hospital Naval Marcılio Dias, Rio de Janeiro, Brazil; Glaucia Pereira Christo Antonioli, MD, Centro Universitario Lusıada, Santos - SP, Brazil; Thuany Silva Santos, MD, Hospital Naval Marcılio Dias, Rio de Janeiro, Brazil Follicular mucinosis is a relatively rare inflammatory disease, characterized by the accumulation of mucin and lymphocytes in the infundibular portion of the pilosebaceous unit, promoting total and irreversible destruction of the affected area. It can be classified as primary, benign and self-limited, with few lesions restricted to the cephalic extremity of children or young adults; prolonged primary form, more common in older individuals, with more generalized lesions in the extremities, face and trunk, and a course many times superior to two years; and in the secondary form associated to other processes, especially mycosis fungoidesetype cutaneous T-cell lymphoma. Histopathology is essential in the diagnosis, and is characterized by mucinous degeneration in the external sheath of the hair follicle and sebaceous gland, in addition to inflammatory infiltrate of lymphocytes, macrophages and eosinophils. Despite the possibility of spontaneous regression in the idiopathic forms, one must take into account the use of topical, intralesional or systemic, dapsone, indomethacin, interferons, minocycline corticosteroids and PUVA for the treatment. The treatment of secondary form should be the treatment of the associated disease. We report a case of a male patient, 7 years of age, with development of a few months of single, rounded, erythematous, slightly scaly plaque in the supraciliar region, asymptomatic, with partial alopecia of the right eyebrow. The histopathologic examination revealed perivascular lymphocytic infiltrate without atypia and with scattered intermingled eosinophils. Mucinous degeneration and dilation of the pilosebaceous follicle were demonstrated by staining with Alcian-blue. The patient was diagnosed with primary follicular mucinosis by means of clinical, pathological and immunohistochemical data, and was isolated in this first moment from association with another pathology. The topical treatment was performed with mometasone cream 1 mg/g twice a day for 30 days, observing the significant regression of the lesion. The patient was instructed to undergo annual clinical monitoring and keep an eye on the appearance of new lesions. The knowledge of the uncommon disease and little seen in doctors’ practices, assists in the differential diagnosis of atypical cutaneous lesions that may be confirmed with the histopathologic diagnosis. Commercial support: None identified.
AB68
J AM ACAD DERMATOL
3300 Prospective study of cutaneous adverse effects associated with BRAF inhibitor dabrafenib and MEK inhibitor trametinib: A study of 12 patients Jean-Philip Lacroix, MD, McGill University, Montreal, Quebec, Canada; Beatrice Wang, MD, McGill University, Royal-Victoria Hospital, Montreal, Quebec, Canada; Catalin Mihalciouiu, MD, McGill University, Royal-Victoria Hospital, Montreal, Quebec, Canada Background: Dabrafenib, a novel selective small molecule inhibitor of BRAF, has been shown to increase progression-free survival and overall survival in patients with unresectable metastatic melanoma harboring the BRAFV600E mutation. The development of resistance has led to the combination therapy with selective MEK inhibitor trametinib. These novel small molecule inhibitors are associated with adverse cutaneous side effects. Compared to vemurafenib, dabrafenib is a more recent BRAF inhibitor FDA approved in May 2013 for metastatic melanoma; less data is available in the current literature regarding cutaneous toxicity, mainly because of its more recent use. Objective: We sought to present additional cutaneous side effects of dabrafenib and trametinib, follow their evolution and management. Methods: We carried out a prospective study of 12 patients treated with dabrafenib alone or in combination with trametinib. Patients were followed every 4 weeks and we collected detailed dermatologic symptoms, photos and biopsy specimens, which enabled us to classify the cutaneous side effects. Results: All patients presented with at least one adverse skin reaction. The mean duration of treatment was 24 weeks. The most common adverse effect was verrucous keratosis (6/12), followed by palmoplantar hyperkeratosis (5/12) and alopecia (4/12). Two patients developed a seborrheic dermatitis-like eruption of the face. Two patients who received dabrafenib and trametinib developed an acneiform eruption (2/3). One patient developed a keratoacanthoma-like squamous cell carcinoma. We report no photosensitivity and no morbilliform eruptions in our cohort. Side effects presented as early as 2 weeks after starting therapy, with a mean time of onset of 8.1 weeks. Conclusion: Selective BRAF inhibitor dabrafenib and MEK inhibitor trametinib are associated with multiple skin adverse effects that have an impact on patient’s quality of life. Given their recent approval and the potential for malignant lesions to develop on treatment, awareness of potential adverse effects and their management is necessary. Commercial support: None identified.
MAY 2016