EJA cop somm_Stesura D’Alessandro 09/07/12 17:06 Pagina 1

Volume 3 - Number 1/2012 EJA cop somm_Stesura D’Alessandro 09/07/12 17:06 Pagina 3

EuVropoelaun mJouern a3l ,o fN Acunem anbd eRrel a1te/d2 D0is1ea2ses Volume 3, n. 1, 2012

The 6th edition of Day will take place Therefore it has to be considered in the beautiful setting of Naples, a complex medical, aesthetical, at Palazzo Salerno Army Officers Club, Giuseppe Monfrecola psychological and social problem. on 14-15 September 2012. The Acne Day 2012 represents The meeting, sponsored by a good opportunity to discuss about the Italian Acne Board, has been organized the many faces of acne by Giuseppe Monfrecola, Dept. of Dermatology and in particular University of Naples Federico II. the newest knowledges about Acne, one of the most frequent skin disorders, its pathogenetic mechanisms strongly influences the quality of life and therapeutic approaches useful of adolescents and young adults. for active phases, maintenance and scars.

3 EJA cop somm_Stesura D’Alessandro 09/07/12 17:06 Pagina 5

Volume 3, Number 1/2012

Editorial Board Content : a case report pag 5 Editor Elena Guanziroli, Franco Greppi, Mauro Barbareschi Stefano Veraldi Milano Refractory SAPHO syndrome in association Co-Editor with resistant E. coli cutaneous infection pag 9 Mauro Barbareschi Milano Caterina Fabroni, Carla Cardinali, Antonia Gimma, Giovanni Lo Scocco Scientific Board Vincenzo Bettoli Ferrara Treatment of comedonal-papular, mild acne with Stefano Calvieri Roma a fixed combination of hydroxypinacolone retinoate, Gabriella Fabbrocini Napoli retinol glycospheres and papain glycospheres. Giuseppe Micali Catania Preliminary results of a sponsor-free, pilot, open, Giuseppe Monfrecola Napoli multicentre study pag 13 Nevena Skroza Roma Stefano Veraldi, Rossana Schianchi Annarosa Virgili Ferrara Managing Editor Antonio Di Maio Milano

Italian Acne Club Mario Bellosta (Pavia), Enzo Berardesca (Roma), Carlo Bertana (Roma), Alessandro Borghi (Ferrara), Francesco Bruno (Palermo), Maria Pia De Padova (Bologna), Paolo Fabbri (Firenze), Carlo Pelfini (Pavia), Mauro Picardo (Roma), Maria Concetta Potenza (Roma), Marco Romanelli (Pisa), Alfredo Rossi (Roma), Patrizio Sedona (Venezia), Riccarda Serri (Milano), Aurora Tedeschi (Catania), Antonella Tosti (Bologna/Miami), Matteo Tretti Clementoni (Milano) International Editorial Board Zrinka Bukvic Mokos (Zagreb, Croatia), Tam El Ouazzani (Casablanca, Morocco), May El Samahy (Cairo, Egypt), Uwe Gieler (Giessen, Germany), Marius-Anton Ionescu (Paris, France), Monika Kapinska Mrowiecka (Cracow, Poland), Nayera Moftah (Cairo, Egypt), Nopadon Noppakun (Bangkok, Thailand), Gerd Plewig (Munich, Germany), Robert Allen Schwartz (Newark, Usa), Jacek Szepietowski (Breslau, Poland), Shyam Verma (Ladodra, India).

Editorial Staff Direttore Responsabile: Pietro Cazzola Consulenza grafica: Piero Merlini Direttore Generale: Armando Mazzù Impaginazione: Stefania Cacciaglia

Registr. Tribunale di Milano n. 296 del 01/06/2011. È vietata la riproduzione totale o parziale, con qualsiasi mezzo, Scripta Manent s.n.c. Via Bassini, 41 - 20133 Milano di articoli, illustrazioni e fotografie senza l’autorizzazione scritta dell’Editore. Tel. 0270608091/0270608060 - Fax 0270606917 L’Editore non risponde dell’opinione espressa dagli Autori degli articoli. E-mail: [email protected] Ai sensi della legge 675/96 è possibile in qualsiasi momento Abbonamento annuale (3 numeri) Euro 50,00 opporsi all’invio della rivista comunicando per iscritto Pagamento: conto corrente postale n. 20350682 la propria decisione a: intestato a: Edizioni Scripta Manent s.n.c., via Bassini 41- 20133 Milano Edizioni Scripta Manent s.n.c. Stampa: Arti Grafiche Bazzi, Milano Via Bassini, 41 - 20133 Milano 01 Guanziroli art_Stesura D’Alessandro 09/07/12 17:09 Pagina 5

European Journal of Acne and Related Diseases

Volume 3, n. 1, 2012

Elena Guanziroli, Franco Greppi, Mauro Barbareschi Department of Anaesthesiology, Intensive Care and Dermatological Sciences, Università degli Studi di Milano, Fondazione IRCCS, Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy

Steatocystoma multiplex: a case report

SUMMARY i l o r i z

n Steatocystoma multiplex (SM) is a squamous epithelium lines the intradermal . a u G

rare inherited or sporadic disorder or atrophic sebaceous elements are a n e

l characterized by multiple, round, constituently present adjacent to or within the wall. E firm, yellow to skin-colored, mobile Various treatment options include surgical excision, CO2 cystic papules and nodules of variable size. laser therapy, cryotherapy, oral antibiotics, and oral They are usually distributed on chest, but can also isotretinoin. involve the entire trunk, face, scalp, arms, axillae, thighs Here, we present a patient with asymptomatic, skin-col- and, more rarely, the genitalia. Incision of the cysts ored nodules on the chest. They were histopathologically releases an oily, milky or yellowish, odourless fluid, or diagnosed as SM. cheesy, solid material. Because the patient had no cosmetic or functional com- On histological examination, a thin wall of stratified plaint, no treatment was considered.

Key words: Steatocystoma multiplex, Eruptive vellus hair cyst.

Introduction

Steatocystoma multiplex (SM) is an face of the epithelial cyst wall 5. uncommon cutaneous disorder that is often inher- Non-inflamed lesions are asymptomatic and except ited as an autosomal dominant trait, resulting from for cosmetic problems, there is no need for treat- a mutation of keratin 17 on chromosome 17 1. ment. Onset is usually around adolescence or early adult life, when the activity of pilosebaceous glands increases 2. Case report It is characterized by multiple cutaneous cystic lesions 1-30 mm in size, which are most common- A 43 year-old man presented with an 28 ly found on the trunk, neck, axillae, and inguinal year history of multiple, asymptomatic nodules on region 3. SM should be differentiated from other the chest. The lesions had first appeared when he cystic lesions such as eruptive vellus hair cysts, was an adolescent and had gradually increased in epidermoid cysts, hidrocystomas, and persistent size and number. milia, but these conditions are often clinically very There was no family history of note. similar, and histological examination is needed to Skin examination showed multiple, smooth, skin- make a correct diagnosis 4. The distinctive features colored, freely movable nodules of soft consisten- of SM are the intramural sebaceous glands, the cy on the sternal region, which varied in size absence of a granular layer, and the crenulated sur- between 8 mm and 1.5 cm (Figure 1). 5 01 Guanziroli art_Stesura D’Alessandro 09/07/12 17:09 Pagina 6

European Journal of Acne and Related Diseases

Volume 3, n. 1, 2012

Figure 1

Figure 1 Clinical aspect of steatocystoma multiplex.

Figure 2 Figure 3

Figure 2 Figure 3 An enfolded cyst wall consisting of two or three layers The crenulated surface of the epithelial cyst wall. of squamous epithelium.

6 01 Guanziroli art_Stesura D’Alessandro 09/07/12 17:09 Pagina 7

European Journal of Acne and Related Diseases

Volume 3, n. 1, 2012

A single nodule of the upper chest was excised. Steatocystoma also occurs as a solitary, noninher- Biopsy specimens revealed a well-encapsulated ited tumor referred to as steatocystoma simplex 13. cyst with an enfolded wall consisting of a thin Histopathologically, steatocystomas are well- layer of stratifying epithelium characterized by a encapsulated dermal cysts with enfolded walls crenulated surface, without a granular layer and lined by stratified squamous epithelium without a without hairs in the lumen (Figure 2-3). granular layer. These histological findings were consistent with a Sebaceous glands, either associated with the cyst diagnosis of SM. or within its wall, are routinely detected. We informed the patient on the benign nature of Occasionally, vellus hairs fragments and amor- the lesions and we illustrated to him the treatment phous keratin material may be found in the cyst possibilities that could be applied in case the cysts space which usually appears empty 3, 5. would become an aesthetic or functional problem It has been reported in association with pachyony- for him. chia congenita, acrokeratosis verruciformis, hyper- trophic , hypohydrosis, hypothy- roidism, suppurativa, ichthyosis, hypo- Discussion trichosis, and multiple keratoacanthomas 14. Differential diagnosis include eruptive vellus hair SM is a nevoid tumor of the sebaceous cysts, epidermoid cysts, persistent milia, acne con- gland duct and acini 6. globata, and beard pseu- It is thought to be inherited in an autosomal domi- dofolliculitis 9. nant fashion, but many sporadic cases have also Occasionally, multiple adnexal tumors, especially been reported 2, 7. if cystic, such as hidrocystomas, may be identical. Mutation of keratin 17, a protein found in several Its relation with eruptive vellus hair cysts has been epithelial structures such as ungual lay, hair folli- a matter of debate. These two diseases have some cles and sebaceous glands has been associated with overlapping features such as clinical appearance familiar SM, as well as with congenita and mode of inheritance, and moreover, there are type 2 1. reports of hybrid forms showing histological fea- Onset occurs during adolescence or early adult life tures of both SM and eruptive vellus hair cysts, but it has also been described at birth and in the leading to the suggestion that they are related con- sixth decade 8, 9. ditions, representing nevoid malformations of the Multiple, widespread cutaneous cystic lesions are pilosebaceous duct junction 15, 16. However, keratin characteristic. They can appear anywhere on the expression pattern studies and immunohistochem- body but they are more common in areas where the ical analysis revealed some major differences pilosebaceous apparatus is well developed, such as between SM and eruptive vellus hair cysts 5, 17. the trunk (especially the sternal area), neck, axil- SM is basically a cosmetic concern to patients but it lae, and inguinal region 3. represents a chronic and difficult-to-treat condition. Some cases are reported in which the lesions are There is no standard treatment for SM. confined to the scalp 7, face 10, proximal extremi- Prolonged courses of antibiotics have been pre- ties 8, and genitalia 11. scribed. Cryotherapy and dermabrasion have been The cystic nodules range from 1 mm to 3 cm in reported to show limited success 18. size and they are soft and freely movable. They Needle aspiration decreases the size of the lesions grow slowly and they have a content that can be but the result remains only for some months 19. oily or creamy 3. Surgical excision is feasible for larger lesions, but Although the majority of them are asymptomatic, can be cumbersome, especially for multiple in some cases, cysts become severely inflamed and lesions. Moreover, extensive scarring is inevitable suppurate. This rare variant is known as SM sup- and cosmetic results may be disappointing 20. purativum 12. Good cosmetic results without relapse have been 7 01 Guanziroli art_Stesura D’Alessandro 09/07/12 17:09 Pagina 8

European Journal of Acne and Related Diseases

Volume 3, n. 1, 2012

achieved by mini-incisions of smaller cysts with ed in a single session, and it is a minimally invasive drainage of debris and excochleation of the cyst procedure 22. wall 21. Systemic therapy with isotretinoin is recommend-

The use of CO2 laser is an ideal technique for the ed in cases with inflamed and suppurative lesions. treatment of multiple lesions and/or lesions locat- It produces temporary improvement, especially in ed in areas aesthetically important such as the face. those patient whose cysts are rich in sebaceous It does not require anesthesia, the lesions are treat- glands 12, 23.

References

1. Covello SP, Smith FJ, Sillevis Smitt JH et al . Keratin 17 toma multiplex suppurativum with isotretinoin. Br J Dermatol mutations cause either steatocystoma multiplex or pachyony- 1984; 111:246. chia congenita type 2. Br J Dermatol 1998; 139:475-80. 13. Brownstein MH. Steatocystoma symplex. A solitary steato- 2. Magid, ML, Wentzell, JM, Roenigk, HH. Multiple cystic lesions. cystoma. Arch Dermatol 1982; 118:409-11. Steatocystoma multiplex. Arch Dermatol 1990; 126:101-4. 14. Moritz, DL & Silverman, RA. Steatocystoma multiplex treat- 3. Cho SY, Chang SE, Choi JH et al. Clinical and histopatholog- ed with isotretinoin: a delayed response. Cutis 1988; 42:437-9. ic features of 64 cases of steatocystoma multiplex. J Dermatol 15. Jerasutus, S, Suvanprakorn, P, Sombatworapat, W. Eruptive 2002; 29:152-6. vellus hair cyst and steatocystoma multiplex. J Am Acad 4. Patrizi A, Neri I, Guerrini V, Costa AM, Passarini B. Dermatol 1989; 2:292-3. Persistent milia, steatocystoma multiplex and eruptive vellus 16. Kiene, P, Hauschild, A, Christophers, E. Eruptive vellus hair hair cysts: variable expression of multiple pilosebaceous cysts cysts and steatocystoma multiplex. Variants of one entity? Br J within an affected family. Dermatology 1998; 196:392-6. Dermatol 1996; 134:365-7. 5. Riedel C, Brinkmeier T, Kutzne H, Plewig G, Frosch PJ. Late 17. Tomková, H, Fujimoto, W, Arata, J. Expression of keratins onset of a facial variant of steatocystoma multiplex - calretinin (K10 and K17) in steatocystoma multiplex, eruptive vellus hair as a specific marker of the follicular companion cell layer. J cysts, and epidermoid and trichilemmal cysts. Am J Dtsch Dermatol Ges 2008; 6:480-2. Dermatopathol 1997; 19:250-3. 6. Plewig G, Wolff HH, Braun-Falco O. Steatocystoma multi- 18. Notowicz, A. Treatment of lesions of steatocystoma multi- plex: anatomic reevaluation, electron microscopy and autoradi- plex and other epidermal cysts by cryosurgery. J Dermatol Surg ography. Arch Dermatol Res 1982; 272:363-80. Oncol 1980; 6:98-9. 7. Jeong SY, Kim JH, Seo SH, Son SW, Kim IH. Giant steatocys- 19. Sato K, Shibuya K, Taguchi H, et al. Aspiration therapy in toma multiplex limited to the scalp. Clin Exp Dermatol 2009; steatocystoma multiplex. Arch Dermatol 1993; 129:35–7. 34:e318-9. 20. Keefe M, Leppard BJ, Royle G. Successful treatment of 8. Rollins T, Levin RM, Heymann WR. Acral steatocystoma steatocystoma multiplex by simple surgery. Br. J. Dermatol multiplex. J Am Acad Dermatol 2000; 43:396-9. 1992; 127:414. 9. Lima AM, Rocha SP, Batista CM, Reis CM, Leal II, Azevedo 21. Schmook T, Burg G, Hafner J. Surgical pearl: mini-incisions LE. Case for diagnosis. Steatocystoma multiplex. An Bras for the extraction of steatocystoma multiplex. J Am Acad Dermatol 2011; 86:165-6. Dermatol 2001; 44:1041-2. 10. Park YM, Cho SH, Kang H. Congenital linear steatocystoma 22. Rossi R, Cappugi P, Battini M, et al. CO2 laser therapy in a multiplex of the nose. Pediatr Dermatol 2000; 17:136-8. case of steatocystoma multiplex with prominent nodules on the 11. Rongioletti F, Cattarini G, Romanelli P. Late onset vulvar face and neck. Int J Dermatol 2003; 42:302–4. steatocystoma multiplex. Clin Exp Dermatol 2002; 27:445-7. 23. Friedman SJ. Treatment of steatocystoma multiplex and 12. Statham, BN & Cunliffe, WJ. The treatment of steatocys- pseudofolliculitis barbae with isotretinoin. Cutis 1987; 39:506-7. 8 02 Fabroni art_Stesura D’Alessandro 09/07/12 17:11 Pagina 9

European Journal of Acne and Related Diseases

Volume 3, n. 1, 2012

Caterina Fabroni, Carla Cardinali, Antonia Gimma, Giovanni Lo Scocco U.O. Dermatologia, Ospedale di Prato, Prato, Italy

Refractory SAPHO syndrome in association with resistant E. coli cutaneous infection

SUMMARY i n o r b

a SAPHO syndrome (synovitis, acne, and skin abnormalities. F

a

n pustulosis, hyperostosis and osteitis) We review the case of a 37-year-old woman affected by i r e t

a is a rare chronic inflammatory refractory and severe SAPHO syndrome with poor C musculoskeletal disorder of response to medical therapy and with resistant E. coli unknown etiology which includes both osteo-articular infection of the skin.

Key words: SAPHO syndrome, Hidradenitis suppurativa, E. coli infection.

Introduction

The SAPHO syndrome is a rare syn- as non-steroidal anti-inflammatory drugs (NSAIDs), drome described for the first time by Chamot et al. oral isotretinoin, antibiotics, immunosuppressants in 1987 1. Cutaneous lesions mainly include and immunomodulators, radiotherapy and surgery palmo-plantar pustulosis, or ful- with varying results. We report here a patient with minans, psoriasis and/or hidradenitis suppurativa SAPHO syndrome with impressive cutaneous mani- (HS). Skin lesions may precede or follow bony festations and poor response to treatment. involvement or may be absent at the time of pre- sentation of other symptoms in 1/3 of patients. Bone and joint lesions include aseptic osteitis, Case report hyperostosis, and synovitis 2. A 37-year-old wo- Genetic, infectious man presented Figure 1 and immunologi- with draining si- cal factors seem to nuses and ab- be involved in the scesses evolving pathogenesis of with formation of this syndrome. fistulas and disfig- Although Propio- uring scar bridles, nibacterium acnes predominantly in has been some- skin folds and times recovered in anogenital areas. bone biopsies 3, the In addition, the pathophysiologic patient exhibited features remain comedones, cysts, poorly understood. abscesses, dis- Many therapies ha- charging sinuses, ve been used such and scars affect- 9 02 Fabroni art_Stesura D’Alessandro 09/07/12 17:12 Pagina 10

European Journal of Acne and Related Diseases

Volume 3, n. 1, 2012

ing predominantly the back, chest, and buttocks (Figures 1, 2, 3). Nodule-cystic acne was present since adolescence as well as some abscesses on the trunk (Figure 4). She also reported fatigue, joint pain with difficulty in walking and fulfilling daily activities. These symptoms were related mainly to a serum negative arthritis and osteitis that involved especially the sacroiliac and sterno-clavicular joints. The patient reported difficulty in relationships with others and a poor quality of life too. Based on the clinical and radiographic presentation, the SAPHO Figure 2 syndrome associated with severe HS was diag- nosed by rheumatologists ten years ago. She had a family history of nodulo-cistic acne. Her personal anamnesis was negative for other diseases. Laboratory evaluations were normal except for an increase of erythrocyte sedimentation rate (ESR: 120 mm/h) and C-reactive protein (CRP: 5 mg/dL) levels, a microcytic anemia (Hb: 8,5 mg/dL). Hepatitis A, B and C serologies and HLA-B27 were negative. During a recent hospitalization the presence of inflammatory bowel diseases (MICI) was excluded as well as the presence of tumors. Previous ineffec- tive treatment included acitretin, oral isotretinoin, topical and systemic antibiotics, corticosteroids, infliximab and adalimumab. During the adminis- Figure 3 tration of the third dose of infliximab, the patient had developed an idiosyncratic reaction while adalimumab had worsened microcytic anemia (Hb Figure 4 = 7 after two administrations). For this reasons, both these treatments were interrupted. Actually, she was treated by rheumatologist with etanercept (50 mg weekly) with improvement of osteoarticular but not cutaneous symptoms. After having carefully studied the patient's medical his- tory and considering the entity of HS lesions, we started a combination therapy with clindamycin (600 mg/die) and rifampicin (600 mg/die) for 12 weeks. The patient well tolerated this regimen but, after an initial improvement of skin lesions, we observed the appearance of new localized purulent abscesses above the buttocks. Cultures for aerobic and anaerobic bacteria and fungi were positive for extended-spectrum b-lactamases (ESBLs)-produc- ing Escherichia coli (E. coli). 10 02 Fabroni art_Stesura D’Alessandro 09/07/12 17:12 Pagina 11

European Journal of Acne and Related Diseases

Volume 3, n. 1, 2012

After an infectivologist consulting, we stopped The efficacy of anti-tumour necrosis factor (TNF)- etanercept and clindamycin/rifampicin and started alpha therapies in refractory SAPHO is reported in treatment with endovenous Ertapenem (1g daily numerous reports 6, 7. In our case therapy with for 14 days). etanercept did not cause any improvement of the After two weeks, we observed an important skin manifestations while was effective for improvement of the cutaneous lesions with resolu- osteoarticular symptoms. For this reason, we tion of the purulent abscesses and decreasing in decided to add a specific antibiotic therapy for HS. ESR and CRP levels. The patient also understood Literature data show the effectiveness of the com- an ultrasound examination of perianogenital areas bination therapy with clindamycin (600 mg daily) that demonstrated an extensive inflammation in the and rifampicin (600 mg daily) administered for at skin and subcutaneous tissue without involvement least 10 weeks in 80% of patients treated 8-10. The of the underlying fascia and muscles. Multiple mechanism of action of rifampicn/clindamycin is lymphoadenopathies were observed in the inguinal not completed known but is clear that they have regions too. Two weeks after the suspension of both antibacterial and anti-inflammatory effects 10. Ertapenem, a new culture from a cutaneous lesion A large variety of microorganisms has been isolat- of the buttock was negative for bacteria and fungi. ed from HS lesions but their role in the pathogen- For this reason, treatment with etanercept was esis of the disease is discussed. Bacteria are prob- restarted. Currently, 1 month after restarting etan- ably secondary colonizers, which may exacerbate ercept, the patient is symptom-free as concerns the HS, but they are not the primary etiologic agents. joint involvement. Rifampicin is a broad spectrum antibacterial agent that inhibits the growth of the majority of gram positive bacteria as well as of many gram-negative Discussion microorganisms. Clindamycin is a lincosamide antibiotic active against gram positive cocci and In 1987, SAPHO syndrome was proposed most anaerobia bacteria. The contemporary use of as an “umbrella” term for a group of diseases with rifampicin and clindamycin should prevent bacter- similar musculoskeletal manifestations, in particu- ial resistance 11, 12. According to our knowledge, lar hyperostosis of anterior chest wall, synovitis the onset of an infection by multiresistant bacteria and multifocal aseptic osteomyelitis, observed in [in our case an extended-spectrum β-lactamases association with skin lesions 1, 2, 4. Despite recent (ESBLs)-producing E. coli] has never been advances in the understanding of epidemiologic, described as a complication of this therapy. The pathophysiologic mechanisms involved in SAPHO most commonly reported risk factors for the onset syndrome, etiopathogenesis remains poorly under- ESBL-producing E. coli infections are contact with stood. The cutaneous manifestations are present in healthcare centres, recent use of antimicrobial 20% to 60% and are represented also by Sweet agents, and presence of comorbidities 13. Our patient syndrome, and pyoderma gangrenosum in addition had manifestations of HS by at least 10 years. with the most represented 3-5. During this time she had undergone several courses Because of the low incidence and different patterns of antibiotics and immunosuppressive drugs: these of disease expression, most reports describe treat- conditions have undoubtedly facilitated the selec- ment responses from anecdotal cases and small tion of bacterial strain-ESBL producing. series of patients. Currently there are no guidelines Finally, another peculiarity of this case is the for the treatment of this complex syndrome 4. patient's microcytic anemia. This condition has Converging arguments indicate that SAPHO syn- been studied thoroughly by the haematologist who drome can be classified with the inflammatory has ruled out cancer or haematological diseases. spondyloarthropathies, which typically affect the The association between HS and anemia sec- spine. The therapeutic strategy was largely ondary to chronic infection, however, was already inspired by that for spondyloarthropathies 5-7. described by Tennant et al. 5, 14. He found anemia 11 02 Fabroni art_Stesura D’Alessandro 09/07/12 17:12 Pagina 12

European Journal of Acne and Related Diseases

Volume 3, n. 1, 2012

in 23,8 % of subjects with severe HS of the but- the correct therapeutic approach. It is important to tocks and groin for more than 2 years 5, 14. evaluate the association of other comorbidities such SAPHO syndrome, in particular when associated as anemia, Crohn’s disease, follicular occlusion with severe HS, as in our case, it is difficult to treat tetrad, acne vulgaris) that can have implications on and requires an approach multispecialist. The lack of the patients’ psychological balance. Controlled clin- knowledge concerning the etiology and the patho- ical trials on large series are also needed to identify genesis of this syndrome makes difficult to identify widely accepted treatment guidelines.

References

1. Chamot AM, Benhamou CL, Kahn MF, Beraneck L, Kaplan Infliximab. Acta Derm Venereol 2011; 91:70-71 G, Prost A. Le syndrome acnè pustulose hyperostose ostèite 8. Gener G, Canoui-Poitrine F, Revuz JE et al. Combination (SAPHO). Resultats d’une enquete nationale. Rev Rhum Mal therapy with Clindamycin and rifampicin for Hidradenitis sup- Osteoartic 1987; 54:187-196 purativa:a case series of 116 consecutive patients. Dermatology 2. DiMeco F, Clatterbuck RE, Kahn W, McCarthy EF, Olivio A. 2009; 219:148-154 Synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome pre- senting as a primary calvarial lesion. J Neurosurg 2000; 93:693-7. 9. Wall D, Kirby B. Rifampicin and clindamycin for hidradeni- tis J Am Acad Dermatol 2011; 64(4):790. 3. Kotilainen P, Merilahti-Palo R, Lehtonen DP, Manner I, Helander I, Mottonen T, et al. Propionibacterium acnes isolated 10. Mendonça CO, Griffiths CE. Clindamycin and rifampicin from sternal osteitis in a patient with SAPHO syndrome. J combination therapy for hidradenitis suppurativa. Br J Rheumatol 1996; 23:1302-4. Dermatol 2006; 154:977-978. 4. Schilling F. SAPHO syndrome. Orphanet encyclopedia, 11. Hessel H, van der Zee, Boer J, Prens EP, Jemec GBE. The October 2004. Available from: effect of combined treatment with oral clindamycin and oral http:/www.orpha.net/data/patho/GB/uk-SAPHO.pdf rifampicin in patients with hidradenitis suppurativa. Dermatology 2009; 219(2):143-7 5. De Souza A, Solomon GE and Strober BE. SAPHO Syndrome Associated With Hidradenitis Suppurativa Successfully Treated 12. Alikhan A, Lynch PJ, Eisen DB. Hidradenitis suppurativa: a with Infliximab and Methotrexate. Bulletin of the NYU comprehensive review. J Am Acad Dermatol 2009; 60(4):539-61 Hospital for Joint Diseases 2011; 69(2):185-7. 13. Oteo J, Pérez-Vázquez M, Campos J. Extended-spectrum 6. Ben Abdelghani K, Dran DG, Gottenberg JE, Morel J, Sibilia [beta]-lactamase producing Escherichia coli: changing epidemiol- J, Combe B. Tumor necrosis factor-alpha blockers in SAPHO syn- ogy and clinical impact. Curr Opin Infect Dis 2010; 23(4):320-6 drome. J Rheumatol. 2010; 37(8):1699-704. Epub 2010 May 15. 14. Tennant F Jr, Bergeron JR, Stone OJ, Mullins JF. Anemia 7. Brunasso et al. Treatment of Hidradenitis Suppurativa with associated with hidradenitis suppurativa. Arch Dermatol 1968; Tumour Necrosis Factor-alpha Inhibitors: An Update on 98:138-40. 12 03 Veraldi-Schianchi ok_Stesura D’Alessandro 09/07/12 17:13 Pagina 13

European Journal of Acne and Related Diseases

Volume 3, n. 1, 2012

Stefano Veraldi 1, Rossana Schianchi 2 1 Department of Anaesthesiology, Intensive Care and Dermatological Sciences, University of Milan, I.R.C.C.S. Foundation, Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy 2 European Institute of Dermatology, Milan, Italy Treatment of comedonal-papular, mild acne with a fixed combination of hydroxypinacolone retinoate, retinol glycospheres and papain glycospheres. Preliminary results of a sponsor-free, pilot, open, multicentre study

SUMMARY i d l a r

e A fixed combination of 0.1% A ≥50% clinical improvement from baseline was V

o

n hydroxypinacolone retinoate (syn- observed in 32/65 patients (49.2%). A ≤50% clinical a f e t thetic esther of 9-cis-retinoic acid), improvement was observed in 8/65 patients (12.3%). S 1% retinol glycospheres and 2% No change was observed in 24/65 patients (36.9%). papain glycospheres in aqueous gel has been recently One patient worsened (1.5%). introduced into the Italian market in order to reduce irri- Nine patients (13.8%) reported one or more side effects tant contact dermatitis caused by topical retinoids with- (dryness, peeling, erythema, burning sensation). All these out compromising their efficacy side effects occurred during the first three weeks of treat- Primary objectives of this sponsor-free, pilot, open, mul- ment, were very mild or mild in severity and transitory. ticentre study were to evaluate the efficacy and tolerabili- In all patients it was not necessary to stop the treatment. ty of this gel in patients with comedonal-papular, mild Results of this study, based on a high number of evalu- acne of the face. able patients, demonstrate that this fixed combination of Sixty-six patients (22 males and 44 females) were treated 0.1% hydroxypinacolone retinoate, 1% retinol glycos- with the gel once daily for 12 weeks. Acne severity and pheres and 2% papain glycospheres is an effective and treatment efficacy were evaluated by means of the Global safe option for the treatment of comedonal-papular, mild Acne Grading System. acne of the face. A controlled clinical study is necessary Sixty-five patients (98.5%) were considered evaluable. to confirm these data.

Key words: Comedonal-papular acne; mild acne; irritant contact dermatitis; retinoid dermatitis; hydroxypinacolone retinoate; retinol; papain; glycospheres.

Introduction

The most important mechanism of action alone or associated with topical antimicrobials of topical retinoids is on the differentiation and and/or oral antibiotics 6, 7. proliferation of keratinocytes 1, 2. This action facil- The most frequent side effect of topical retinoids is itate the penetration of other anti-acne drugs: topi- irritant contact dermatitis (ICD), also named cal retinoids, and in particular tretinoin, “retinoid dermatitis” (RD) 8, 9. isotretinoin and adapalene, have been successfully ICD is characterized clinically by dryness, peeling, combined (“fixed combinations”) with clin- erythema, scaling, oedema, stinging, burning and damycin, erythromycin and benzoyl peroxide 3, 4. itching 10. RD is very common, occurring, in our Furthermore, the action on differentiation and pro- personal clinical experience, in approximately 85% liferation of keratinocytes induces the expulsion of of patients 10; mature closed and open comedones and the sup- the percentage can reach up to 95% in patients pression of microcomedone formation 5. treated with tretinoin 10. RD usually appears after Since 2003, topical retinoids are considered of first the first applications of the retinoid; very rarely it choice in the treatment of mild to moderate acne, persists for all the duration of the treatment 10. 13 03 Veraldi-Schianchi ok_Stesura D’Alessandro 09/07/12 17:13 Pagina 14

European Journal of Acne and Related Diseases

Volume 3, n. 1, 2012

Severity of RD is mainly due to the type of ed by means of the Global Acne Grading System retinoid: tretinoin and tazarotene can be very irri- (GAGS) 13. tant,11 while retinol and retinaldehyde are not irri- Significant clinical improvement was judged as an tant 12. RD severity is also concentration-depen- improvement ≥50% from baseline. dent and related to the vehicle used: retinoids in alcoholic gel are more irritant 10, 11. Severity of RD is usually mild to moderate and Results duration is changeable, from a few days up to 3-4 weeks. Sixty-five patients (98.5%) were consid- However, in our experience, severity of tretinoin- ered evaluable at the end of the study. induced ICD is moderate to severe in approximate- A ≥50% clinical improvement from baseline was ly 20% of patients 10. Furthermore, always in our observed in 32/65 patients (49.2%); a ≤50% clini- experience, 15% of patients stop the treatment cal improvement from baseline was observed in with tretinoin because of skin irritation 10. 8/65 patients (12.3%); no change was observed in RD improves after treatment suspension or by 24/65 patients (36.9%); one patient worsened application of moisturizers or, in more severe (1.5%). cases, of low- to mid-potency corticosteroids 10. Nine patients (13.8%) reported at least one side A fixed-combination of 0.1% hydroxypinacolone effect. All side effects occurred during the first retinoate, 1% retinol in glycospheres and 2% papain three weeks of treatment, were very mild or mild in in glycospheres in aqueous gel has been recently severity and transitory. Seven patients (10.8%) introduced into the Italian market with the aim to reported dryness, five (7.7%) mild peeling, three reduce incidence and severity of ICD. (4.6%) erythema and three (4.6%) burning sensa- We present the preliminary results of a sponsor-free, tion. In all patients it was not necessary to stop the pilot, open, multicentre study for the evaluation of treatment. the efficacy and tolerability of this gel in the treat- ment of comedonal-papular, mild acne of the face. Discussion

Patients and Methods ICD due to tretinoin 14, 15, tazarotene 14, isotretinoin 15, 16 and adapalene17 has been exten- Sixty-six patients [22 males (33.3%) and sively studied, both experimentally and clinically. 44 females (66.6%)], with an age ranging from 12 to The risk of ICD has triggered research for new and 50 years (median age: 23.8 years), with comedonal- better tolerated topical retinoids: as previously papular, mild acne located exclusively on the face, mentioned, tolerability is a critical factor for were treated with the gel. Wash-out period was of at patient’s compliance. least 2 months for oral isotretinoin and antibiotics, Hydroxypinacolone retinoate is a new synthetic and 3 weeks for topical retinoids, antiseptics, antibi- esther of 9-cis-retinoic acid. Retinol is one of the otics, azelaic acid, salicylic acid and nicotinamide. best known cosmeceutical forms of vitamin A 18. The gel was applied once daily, in the evening. The Papain is a hydrolase extracted from Carica application was preceded by a cleaning. No other papaya ripe fruit 19. Other ingredients of this gel topical and/or systemic products or drugs were are Rebuilt Natural Moisturizer Factor (RNMF) allowed, except for moisturizers, non-- that, thanks to its remarkable hygroscopic charac- genic make-ups and sunscreens. Abrasive teristics, forms a superficial semi-permeable film cleansers and chemical peels were not allowed. and blocks skin dehydration 20; tocopherol, that Treatment duration was 12 weeks. All patients acts as antioxidant 21; alpha-bisabolol, that pos- were clinically evaluated every 4 weeks. sesses anti-inflammatory action 22; glycerol, that Acne severity and treatment efficacy were evaluat- has a moisturizing effect 23; trehalase, a disaccha- 14 03 Veraldi-Schianchi ok_Stesura D’Alessandro 09/07/12 17:13 Pagina 15

European Journal of Acne and Related Diseases

Volume 3, n. 1, 2012

ride with a barrier-like action; and Aloe barbaden- ii) tolerability was very good: approximately 13% sis, that has an antioxidant effect 24. of patients reported local side effects; however, Preliminary results of our study (open, although in all these patients side effects were very mild sponsor-free, multicentre and based on a high or mild in severity and transitory; in fact, it was number of evaluable patients) may be summarized not necessary to stop the treatment. as follows: This very good tolerability allows a high adherence i) this gel seems to be effective in the treatment of of patients, mainly young patients, to the treat- comedonal-papular, mild acne of the face; ment: this gel markedly improves compliance.

References

1. Bikowski JB. Mechanisms of the comedolytic and anti- 13. Doshi A, Zaheer A, Stiller MJ. A comparison of current inflammatory properties of topical retinoids. J Drugs Dermatol acne grading systems and proposal of a novel system. Int J 2005; 4:41-7. Dermatol 1997; 36:416-8. 2. Thielitz A, Krautheim A, Gollnick H. Update in retinoid ther- 14. Phillips TJ. An update on the safety and efficacy of topical apy of acne. Dermatol Ther 2006; 19:272-9. retinoids. Cutis 2005; 75 (Suppl 2):14-24. 3. Richter JR, Förström LR, Kiistala UO, et al. Efficacy of the 15. Domínguez J, Hojyo MT, Celayo JL, et al. Topical fixed 1.2% clindamycin phosphate, 0.025% tretinoin gel formu- isotretinoin vs. topical retinoic acid in the treatment of acne vul- lation (Velac) and a proprietary 0.025% tretinoin gel formula- garis. Int J Dermatol 1998; 37:54-5. tion (Aberela) in the topical control of facial acne. J Eur Acad 16. Chalker DK, Lesher JL Jr, Smith JG Jr, et al. Efficacy of Dermatol Venereol 1998; 11:227-33. topical isotretinoin 0.05% gel in acne vulgaris: results of a mul- 4. Thiboutot DM, Weiss J, Bucko A, et al. Adapalene-benzoyl ticentre, double-blind investigation. J Am Acad Dermatol 1987; peroxide, a fixed-dose combination for the treatment of acne 17:251-4. vulgaris: results of a multicentre, randomized double-blind, con- 17. Waugh J, Noble S, Scott LJ. Adapalene: a review of its use trolled study. J Am Acad Dermatol 2007; 57:791-9. in the treatment of acne vulgaris. Drugs 2004; 64:1465-78. 5. Lavker RM, Leyden JJ, Thorne EG. An ultrastructural study 18. Rossetti D, Kielmanowicz MG, Vigodman S, et al. A novel of the effects of topical tretinoin on microcomedones. Clin Ther anti-ageing mechanism for retinol: induction of dermal elastin 1992; 14:773-80. synthesis and elastin fibre formation. Int J Cosmet Sci 2011; 6. Gollnick H, Cunliffe W. Management of acne. A report from 33:62-9. a global alliance to improve outcomes in acne. J Am Acad 19. Laidet B, Letourneur M. Enzymatic debridement of leg Dermatol 2003; 49:S1-37. ulcers using papain. Ann Dermatol Venereol 1993; 120:248. 7. Thiboutot D, Gollnick H, Bettoli V, et al. Global Alliance to 20. Bouwstra JA, Groenink HW, Kempenaar JA, et al. Water Improve Outcomes in Acne. New insights into the management distribution and natural moisturizer factor content in human of acne: an update from the Global Alliance to Improve skin equivalents are regulated by environmental relative humid- Outcomes in Acne group. J Am Acad Dermatol 2009; 60 (Suppl ity. J Invest Dermatol 2008; 128:378-88. 5):S1-50. 21. Murray JC, Burch JA, Streilein RD, et al. A topical antiox- 8. Cunliffe WJ. Acne. Martin Dunitz, London, 1994; 242. idant solution containing vitamins C and E stabilized by ferulic 9. Heel RC, Brogden RN, Speight TM, et al. Vitamin A acid: a acid provides protection for against damage caused review of its pharmacological properties and therapeutic use in by ultraviolet irradiation. J Am Acad Dermatol 2008; 59:418-25. the topical treatment of acne vulgaris. Drugs 1977; 14:401-19. 22. Jakovlev V, Von Schlichtegroll A. On the inflammation 10. Veraldi S, Schianchi R. Short contact therapy of acne with inhibitory effect of (-)-alpha-bisabolol, an essential component tretinoin. Eur J Acne 2011; 2 (Suppl 1):1-2. of chamomilla oil. Arzneimittelforschung 1969; 19:615-6. 11. Cunliffe WJ, Gollnick HPM. Acne. Diagnosis and manage- 23. Lodén M, Andersson AC, Anderson C, et al. A double-blind ment. Martin Dunitz, London, 2001; 110. study comparing the effect of glycerin and urea on dry, eczema- 12. Saurat JH, Didierjean L, Masgrau E, et al. Topical retinalde- tous skin in atopic patients. Acta Derm Venereol 2002; 82:45-7. hyde on human skin: biologic effects and tolerance. J Invest 24. Goodyear-Smith F. Aloe vera-Aloe vera, Aloe barbadensis, Dermatol 1994; 103:770-4. Aloe capensis. J Prim Care Health 2011; 3:322. 15 03 Veraldi-Schianchi ok_Stesura D’Alessandro 09/07/12 17:13 Pagina 16

European Journal of Acne and Related Diseases

Volume 3, n. 1, 2012 Istructions to Authors Authors’ responsibilities Manuscripts are accepted with the understanding that they have Title of the journal following Index Medicus rules. Year of publi- not been published or submitted for publication in any other jour- cation; Volume number: First page. nal. Authors must submit the results of clinical and experimental Example: Starzl T, Iwatsuki S, Shaw BW, et al. Left hepatic tri- studies conducted according to the Helsinki Declaration on clini- segmentectomy. Surg Gynecol Obstet 1982; 155:21. cal research and to the Ethical Code on animal research set forth by WHO (WHO Chronicle 1985; 39:51). Authors - Complete title in the original language. Edition number The Authors must obtain permission to reproduce !gures, tables (if later than the !rst). City of publication: Publisher, Year of and text from previously published material. publication. nd Written permission must be obtained from the original copyright Example: Bergel DIA. Cardiovascular dynamics. 2 ed. holder (generally the Publisher). London: Academic Press Inc., 1974.

Authors of the chapters - Complete chapter title. In: Book Editor, Manuscript presentation complete Book Title, Edition number. City of publication: Authors must submit the text (MAC and WINDOWS Microsoft Publisher, Publication year: !rst page of chapter in the book. Word are accepted) and illustrations by e-mail. It is also necessary Example: Sagawa K. The use of central theory and system analy- send a picture of the !rst Author. As an alternative manuscripts sis. In: Bergel DH (Ed), Cardiovascular dynamics. 2nd ed. can be submitted by surface mail on disk with two hard copies of London: Academic Press Inc., 1964; 115. the manuscript and two sets of illustrations. Manuscripts must be written in English or in Italian language in accordance with the Tables “Uniform Requirements for Manuscripts submitted to biomedical Tables must be clearly printed and aimed to make comprehension journals” de!ned by The International Committee of Medical of the written text easier. They must be numbered in Arabic digits Journal Editors (http://www.ICMJE.org). and referred to in the text by progressive numbers. Every table Manuscripts should be typed double spaced with wide margins. must be typed on a separate sheet and accompanied by a brief They must be subdivided into the following sections: title. The meaning of any abbreviations must be explained at the bottom of the table itself. Title page It must contain: Figures a) title; (graphics, algorithms, photographs, drawings) b) !rst, middle and last name of each Author without abbrevia- Figures must be numbered and quoted in the text by number. tions; If sent by surface mail !gures must be submitted in duplicate. c) University or Hospital, and Department of each Author; On the back side of each !gure the following data must appear: d) last name and address of the corresponding Author; !gure number, title of the paper, name of the !rst Author, an e) e-mail and/or fax number to facilitate communication; arrow pointing to the top of the !gure. f) list of abbreviations. Please follow these instructions when preparing !les: • Do not include any illustrations as part of your text !le. Summary • Do not prepare any !gures in Word as they are not workable. The Authors must submit a long English summary. • Line illustrations must be submitted at 600 DPI. After the summary, three to ten key words must appear, taken • Halftones and color photos should be submitted at a mini- from the standard Index Medicus terminology. mum of 300 DPI. • Power Point !les cannot be uploaded. Text • Save !gures as either TIFF or JPEG or EPS !les. For original articles concerning experimental or clinical studies • PDF !les for individual !gures may be uploaded. and case reviews, the following standard scheme must be fol- lowed: Introduction - Material and methods - Results - Discussion Figure legends - Conclusions - Summary - References - Tables - Legends - Figure legends must all be collected in one or more separate Figures. pages. The meaning of all symbols, abbreviations or letters must be indicated. Histology photograph legends must include the Size of manuscripts enlargement ratio and the staining method. Literature reviews, Editorials and Original articles concerning experimental or clinical studies should not exceed 20 typewritten Manuscript review pages including !gures, tables, and reference list. Case reports and Only manuscript written according to the above mentioned rules notes on surgical technique shouid not exceed 10 type written will be considered. All submitted manuscripts are evaluated by pages (references are to be limited to 12). Letters to the editors the Editorial Board and/or by two referees designated by the should be not longer than 1000 words. Editors. The Authors are informed in a time as short as possible on whether the paper has been accepted, rejected or if a revision References is deemed necessary. The Editors reserve the right to make edito- The Author is responsible for the accuracy of the references. rial and literary corrections with the goal of making the article References must be sorted in order of quotation and numbered clearer or more concise, without altering its contents. Submission with arabic digits between parentheses. Only the references quo- of a manuscript implies acceptation of all above rules. ted in the text can be listed. Journal titles must be abbreviated as in the Index Medicus. Only studies published on easily retrieved Papers submitted for publication and all other editorial corre- sources can be quoted. Unpublished studies cannot be quoted, spondence should be addressed to: however articles “in press” can be listed with the proper indica- tion of the journal title, year and possibly volume. Antonio Di Maio European Journal of Acne and Related Diseases References must be listed as follows: Edizioni Scripta Manent Via Bassini, 41 - 20133 Milano, Italy All Authors if there are six or fewer, otherwise the !rst three, fol- Tel. 0270608091 - Fax 0270606917 lowed by “et al.”. Complete names for Work Groups or E-mail: [email protected] Committees. Complete title in the original language. [email protected] 16 EJA cop somm_Stesura D’Alessandro 09/07/12 17:06 Pagina 7