Potential links of Interests

• In the past 2 years, I (or my department) have received honoraria for lectures on STDs (BMS) or for participation in advisory boards on TBE (Baxter) or KS (Gallen) • I am the Editor in Chief of the Journal of Travel Medicine (IF = 1.7) Dermatoses tropicales • Introduction • Données épidémiologiques • cutanées bactériennes • Larva migrans cutanée ankylostomienne • Leishmaniose cutanée localisée • Dermatoses prurigineuses • Dermatoses marines • Exanthème fébrile • Dépigmentation volontaire Dermatoses tropicales ??

• Dermatoses vues dans les pays tropicaux • Dermatoses vues dans les pays occidentaux .Voyageurs . Immigrés Consultations médicales au retour de voyage

7767 suisses(1) 8 % 2109 italiens(2) 11 % 779 américains(3) 12 % 200 israeliens(4) 19 %

(1) Steffen et al ; J Inf Dis 1987;156:84-91 (2) Bruni et al ; J Travel Med 1997;4:61-64 (3) Hill D ; J Travel Med 2000;7:259-266 (4) Winer ; J Travel Med 2002;9:227-232 Part des dermatoses dans les consultations médicales au retour

93 américains (1) 11 % (4eme) 622 français (2) 24 % (2eme) 17343 Monde (3) 17 % (3eme)

(1) Hill D. J Travel Med 2000;7:259-266 (2) Freedman DO et al. N Engl J Med 2006; 354: 119-130 (3) Ansart S et al. Am J Trop Med Hyg 2007; 76 : 184-186 Part des dermatoses exotiques, tropicales, parmi les dermatoses au retour 224 francais (269) (1) 54 % (1995,Hosp) 114 français (149) (2) 34 % (2007,Hosp) 4594 Monde (4742) (3) 24 % (GeoSent) 10 américains (4) 0 % (ville)

(1) Caumes E et al. Clin Inf Dis 1995; 20 : 542-548 (2) Ansart S et al. Am J Trop Med Hyg 2007; 76 : 184-186 (3) Freedman DO et al. N Engl J Med 2006; 354: 119-130 (4) Hill D. J Travel Med 2000;7:259-266 What is the most common skin disease diagnosed in returning travellers :

1. Myiasis 2. Syphilis 3. Skin and soft tissue infections 4. related 5. Arthropod related dermatitis The top nine travel associated dermatoses* in 4594 pts, 1997-2006, WW travellers (GeoS)

• Cutaneous larva migrans : 465 (10%) • Insect bites : 388 (8%) • Abcess (pyoderma) : 366 (7%) • Surinfected insect bites : 324 (7%) • Cutaneous allergy : 263 (5%) • Rash of undetermined origin : 262 (5%) • Bite by : 203 (4%) • Superficial mycose : 190 (4%) SSTI : 690 • Dengue : 159 (3%) (15%) * 24% tropical;

Lederman E et al. Int J Inf Dis 2008, i:10.1016/j.ijd.2007.12.008 The top nine travel associated dermatoses* in 114 pts, 2000s, tourists, migrants, expat

• Infectious cellulitis : 21 (14%) • Scabies : 17 (11%) • PUO : 15 (10 %) • Pyoderma : 14 (9%) • Myiasis : 12 (8%) • Tinea : 10 (6%) SSTI : 35 • : 9 (6%) • Cutaneous Larva migrans : 8 (5%) (23%) • Urticaria : 8 (5%)

* 76 % of 149 dermatoses (34% tropical)

Ansart S et al. Am J Trop Med Hyg 2007; 76 : 184-186 Dermatoses in 8.227 ill travelers (19%), GeoSentinel, 2007-2011

Rabies PEP required in 12% 18% CLM = 8% of all skin pbs 16% 14% 12% 10% 8% Derm 6% 4% 2% Sentinel 0% SSTI Insect itch

Leder K et al. Ann Intern Med 2013; 158: 456-468 www.medecine-voyages.fr Regarding SSTI acquired during travel in tropical countries, the main cause of concern is :

1. Unusual culprit microbial agent 2. Atypical clinical appearance 3. Importance of serologic results 4. Fear of antibiotic resistance 5. Stool examination Inf Cutanées bactériennes (n = 48)

• Impétigo : 19 (39%) - S aureus (40%) [12 (63%) avec piqure/ - Streptococcus sp (20%) morsure d’arthropode] - S. aureus + st (20%) - négative (20%) • Erysipèle : 9 (18%) • Ecthyma : 8 (16%) • Abces : 4 (8%) • Furoncle : 4 (8%) • Intertrigo : 2 (4%) • Folliculite : 1 (2%) • DHBA nécrosante : 1 (2%)

Caumes et al - Clin Inf Dis 1995;20:542-548 Infections cutanées bactériennes chez 60 voyageurs; 01/2006-08/2007

Formes N (%) % culture + Sa MS SGA Les 2

Impetigo 21 (35%) 76% 31% 38% 31%

Abces 14 (23%) 57% 0100% 0

Ecthyma 11 (19%) 91% 10% 60% 30%

Cellulite (19%) 011 NA NA NA

Folliculite 3 (5%) 33% 0100% 0

Hochedez P et al. Am J Trop Med Hyg 2009; 80: 431-4

Insect bite, impetigo, cellulitis

Insect bite, cellulitis, Abcess, fistulisation to the skin Erysipela vs infectious cellulitis Erysipela vs infectious cellulitis –Peripheral surelevated borderline –Clear borderline with surrounding tissues

Bisno AL. N Engl J Med 1996; 334:240-245

« In practice, distinguishing between cellulitis and erysipelas clinically may be difficult…. »

Stevens DL. Clin Infect Dis 2005; 41: 1373-1406 Criteria of severity when facing an infectious cellulitis

• No clinical response to antibiotherapy • Intense and constant pain (+++) • Cutaneous oedema reaching surrounding tissues • Cutaneous necrosis (blue, white then black) • Gaz (crepitation, Xray) • Loss of cutaneous sensitivity (+++) • Having clinical signs of severe infections

Stevens DL. Clin Inf Dis 2005; 41: 1373-1406 Regarding S.aureus related SSTI acquired while being in the tropics, the main causes of concern are: • Transmission in the household • Antibiotic resistance • Reccurences • Portage • All of them Femme, 35 ans, Homme, 41 ans, Retour de Apparition Cote d’Ivoire à J6 des retrouvailles Femme, 35 ans; lendemain d’un retour de voyage en Côte d’Ivoire (J 3 lésion)

J 1 : piqure d’insecte J 4 : apparition de la lésion cutanée J 6 : retour; J 7 : consultation Homme de 41 ans, compagnon de N°1 Lésion cutanée localisée sur le pied droit apparue 6 jours aprés les “retrouvailles” avec N°1 Lésion cutanée à J5 de l’évolution spontanée …… Male, 33 y, just returning from Fiji Female, 29 y, wife of Mr Fiji and companion of travel Mr Abcess & Mrs impetigo cellulitis

MS PVL+ S. aureus Import and spread of PVL+ S.aureus in travelers with SSTI

• 38 travelers with S.aureus + SSTI vs 124 control with other trav-dis; genotyping • S.aureus SSTI were associated with travel duration and location (: OR =4.2) • Pts with PVL+ S.aureus SSTI were also colonized in the nares (73% vs 25%) • SSTI due to PVL+ S.aureus were more likely to be complicated, reduced antibiotic susceptibility and 2ry spread (5 clusters)

Zanger P et al. Clin Inf Dis 2012; 54: 483-92 Import and spread of PVL+ S.aureus in travelers with SSTI

Sa+ nasal PVL+ nasal PVL+ lesion carriage carriage Abscess 0.5 0.1 0.001 Furuncle Recurrent 0.4 0.002 0.001 Disease Surgical 1 0.2 0.015 drainage SSTI contacts 1.8 0.1 0.1

Zanger P et al. Clin Inf Dis 2012; 54: 483-92 Traveling MRSA Imported MRSA in Sweden, 2000-2003 • 1733 cases MRSA reported in Sweden • 444 (25 %) imported cases (acquired abroad) * 292 (65 %) in Swedish travellers * 56 (12 %) in newly arrived immigrants * 40 (9 %) in internat adopted children * 30 (7 %) in foreign residents * 20 (4 %) in Swedish expatriates • Including 246 (55 %) HA and 146 (33 %) CA

Stenhem M et al. Emerg Inf Dis 2010;16:189-196 MRSA Imported by Swedish travelers 2000-2003 : countries at risk (ORs) • Nordic 0.1 (0.01-0.6) • Western Europe Reference* • Southern Europe 2.4 (1.0-5.8) • Central and Eastern Europe 2.8 (1.0-8.1) • UK and Ireland 10.3 (4.4-24.0) • North America 10.6 (4.2-26.7) • Northeastern Mediterranean 15.8 (7.0-35.6) • South America 31.2 (10.0-97.6) • East 36.5 (16.2-82.0) • Oceania and Pacific Islands 43.0 (15.5-119.4) • Sub-Saharan Africa 46.3 (17.3-123.6) • North Africa and Middle East 59.0 (25.1-138.9)

Stenhem M et al. Emerg Inf Dis 2010;16:189-196 Abscess management

• « Ubi pus, Ibi evacuata »

Still true since Hippocrate

Am J Med 1876; 6: 226 In case of recurrent S.aureus SSTI, the followings can be proposed:

• Education • Mupirocin • Antiseptic wash • None of them • All of them Staphylococcal decolonisation in pts with recurrent SSTI: effective?

Ref N= S.aureus FU Tt vs P(or E) P = Raz MSSa34 12 m M monthly 0.002 Ellis 134 CA-MRSa 4 m M /5 days 0.76 Gordon 92 27%-MRSa 6-8 m M monthly NS Fritz 300 68%MRSa 6 m E + M (5 d) 0.4

M: mupirocin; E: education; E + M + Chl 0.51 P: Placebo; Chl: Chlorhexidine BB: Bleach baths E + M + BB 0.02

Simar AE. Lancet 2011; 11: 952-962 Decolonization for prevention of recurrent CA-MRSA infections • California, private practice, 31 pts enrolled • Mean age : 40 y; 58% Female; 86% healthy • Mean Nb of episodes < 6 mths = 5 (2-30) • 10 d regimen:nasal mupirocin 2/d, body wash hexachlorophene/d + AB (cycl; tmp/smx) • Mean rate = 0.03 inf/month > 6 mths (FU period) vs 0.84 inf/mth < 6 mths intervention (P < 0.0001)

Miller LG et al. Antimicrob Ag Chemoth 2012; 56: 1085-86 Infections cutanées bactériennes

• Streptocoques et staphylocoques sont responsables d’infections plus ou moins sévères selon le terrain et la profondeur de l’atteinte cutanée • Streptococcus pyogenes: toujours sensible aux pénicillines (G,A,…), résistance aux macrolides rendant aléatoire le traitement par les antibiotiques du groupe MLSK • Staphylococcus aureus: toujours plus résistant, notamment diffusion mondiale progressive des SARM an ville; pristinamycine (MLSK) efficace Larva migrans cutanée ankylostomienne (larbish)

• Même si tout ce qui court sous la peau ne relève pas de la larva migrans cutanée ankylostomienne (HrCLM) • HrCLM reste la cause la + fréquente de dermatite rampante exception faite de quelques pays (Japon….) Boracay, Philippines LMC ankylostomienne c° voyageurs

Ref (1) (2) (3) Patients 60 67 64 Nationalité Canada France France > Retour 45 % 51 % 55 % Délai/Retour 5j (0-30) 8j (0-28) 16j (1-120)

(1) Davies et al. Arch Dermatol 1993;129:588-591 (2) Caumes et al. Clin Infect Dis 1995;20:542-548 (3) Bouchaud et al. Clin Infect Dis 2000;31:493-498

Courtesy F.Ly (Dakar, Sénégal) Folliculitis (HrCLM)

Diagnosis of HrCLM relies on :

1. Epidemiological data 2. Clinical appearance and course 3. Biopsy of local lesion 4. Serologic studies 5. Stool examination Diagnosis of HrCLM relies on :

1. Epidemiological data : typical exposure 2. Clinical appearance : creeping dermatitis (but also pruritic folliculitis) 3. Course of the disease : appearance less than one month after return, chronic 4. Biopsy of local lesion useless (except in folliculitis) 5. Stool examination : no interest except in ……dogs You have made the diagnosis of hookworm related cutaneous larva migrans. You could confirm your clinical suspicion by…. • Confocal microscopy • Histological examination • Optical microscopy • PCR which allows species identification • All of these • None of these Confocal microscopic identification of hookworm larvae in HrCLM (Purdy KS et al. Lancet 2011; 377: 1948) (A)Serpiginous eruption of plantar aspect of right foot. (B) Reflectance confocal microscope imaging showing highly refractile oval larva (arrow). (C) Histological examination of punch biopsy extraction showing richly eosinophilic intact hookworm larva (arrow) within the epidermis. Identification of Ancylostoma braziliense in HrCLM (Le Joncour A et al. Am J Trop Med Hyg 2012; 86:843-5) hookworm larva recovered from a skin scraping of folliculitis Lesion (optical micro, x40)

Living hookworm larva recovered from a skin scraping of folliculitis Lesion (optical micro, x10)

Le Joncour A et al. Am J Trop Med Hyg 2012; 86:843-5 You have made the diagnosis of hookworm related cutaneous larva migrans. You could have confirmed your clinical suspicion by….

• Confocal microscopy • Histological examination • Optical microscopy • PCR

But in daily practice we relie on epidemiological and clinical grounds …. and the answer to « specific » treatment Hr Cut larva migrans in travellers

Ref (1) (2) (3) Patients 60 67 64 Nationality Canada France France After return 45 % 51 % 55 % Lagtime 5d (0-30) 8d (0-28) 16d (1-120)

(1) Davies et al. Arch Dermatol 1993;129:588-591 (2) Caumes et al. Clin Infect Dis 1995;20:542-548 (3) Bouchaud et al. Clin Infect Dis 2000;31:493-498 LMC ankylostomienne chez voyageurs

Ref (1) (2) (3) Patients 60 67 64 Nb lésions/pt 1(1-6) 1(1-24) 3(1-15) Infection 17 % 6 % 8 % Vésiculobulle 9 % 10 %

(1) Davies et al. Arch dermatol 1993;129:588-591 (2) Caumes et al. Clin Infect Dis 1995;20:542-548 (3) Bouchaud et al. Clin Infect Dis 2000;31:493-498

You are going to treat this patient with…

• Ivermectine single dose • Ivermectine double dose • Albendazole 800 mg/d, 3 days course • Albendazole 400 mg/d, 5 days course • None of these • All of these Traitement de LMC ankylostomienne Local • (thiabendazole) • (flubendazole) • Albendazole 10% crotamiton Oral • (thiabendazole : 50 mg/kg/j x 2- 4 j) • albendazole : 400-800 mg/j x 3 j • ivermectin : 12 mg dose unique (adultes)

Caumes E. Clin Inf Dis 2000; 30: 811-14 4 Treatment of HrCLM : ivermectin, 12 mg

• 51 patients (28 H, 23 F) • Median age : 30 (1-69)

• Succes : 50/51 (98 %) Cured within 5 days (n = 48) Cured after 7 and 10 days (n = 2) Relapse : 2/50 • Relapse (ID) : 1/51 (2%)

Van den Enden et al - NEJM 1998 ; 339 : 1246-1247

HrCLM : efficacy of a single dose ivermectin varies with the clinical presentation.

• 62 travellers (35 F, 27 M, mean age 35) with HrCLM treated with 200 µg/kg dose of ivermectin, single dose. • All pts had creeping dermatitis and 6 patients (10%) also had hookworm folliculitis (HF). • Overall CR = 59/62 pts (95%). CR = 98% in the 56 pts presenting with only creeping dermatitis and 66% in the 6 patients also presenting with HF

Vanhaecke C et al. J Eur Acad Dermatol Venereol 2013

Topical albendazole in CLM : 2 pts

• 2 children, 10 kgs, 2 years old • Return from Senegal, Dominican Republic • 1 cutaneous lesion/pt • ivermectin and albendazole contra indicated • thiabendazole no more marketed • albendazole ointment 10% (3 tablets, i.e. 1200 mg, mixed with 12 gr crotamiton) twice a day during 10 days

Caumes E ; Clin Inf Dis 2004; 38: 1647-1648 A traveler wants to know how to avoid HrCLM on his next vacation. Your advice to him is :

1. Use insect repellent 2. Sleep under bednets 3. Protect skin against direct sand/soil exposure 4. Make dogs wearing sun glasses 5. Make dogs clean their shit Beppu, Japan Taipei, Taiwan Tokyo, Japan

Tokyo Borracay, Philippines

Dermatite rampante et larva migrans cutanée

Tout ce qui migre sous la peau n’est pas toujours une larva migrans cutanée ankylostomiennne (larbish) voire même une cause du syndrôme de larva migrans cutanée Dermatite rampante vs LMC

Un signe = dermatite rampante vs Un syndrôme = larva migrans cutanée

- larva migrans cutanée ankylostomienne (HrCLM) - Gnathostomose (larve de nematode)

- Anguillulose (larva currens) (larve de nématode) - Loase () (nematode) - Myiase rampante (asticot) - Gale (acarien) - …….. Caumes E. Dermatology. 2006;213:179-81. 7070 patientspatients withwith creepingcreeping dermatitisdermatitis,, 20082008-- 2012,2012, PitiPitiéé SalpêtriSalpêtrièèrere hospitalhospital

Disease Number of cases (%) HrCLM including 66 (94%) Hookworm folliculitis 7 (11%) 2 (3%) Loiasis 1 (1.5%) Creeping (dog) hair 1 (1.5%)

Migratory myiasis, 0 , larva currens

Van Haecke C et al. Br J Dermatol 2013 Larva currens () Strongyloidiasis in travellers

• High seroprevalence of S stercoralis infection (6%) found in NZ police deployed overseas (Visser JT et al. J Travel Med 2012, 19: 37-41) • 0.25% (rate of 3.2/1,000 person months) were found to seroconvert for S stercoralis in short- term dutch travelers (Baaten Get al, BMC Infect Dis 2011; 11:84) • 0.8% of returning travelers had a positive S stercoralis polymerase chain reaction (ten Hove RJ et al. Eur J Clin Microbiol Infect Dis 2009; 28:1045–1053 ) Single and Double (D 14) Ivermectin versus 7- Day Albendazole for Strongyloidiasis.

ALB x 7 d IVE X1 IVE X2 800 mg/d 200µg/kg 200µg/kg N = 30 31 29

FU duration 19 wks 39 wks 26 wks (2–76) (2–74) (2–74) Cure rate 63% 96% 93% (P = 0.006) Suputtamongkol Y, et al. PLoS Negl Trop Dis 2011; 5: e1044 Single Ivermectin versus 2 days Thiabendazole for Strongyloidiasis.

Criteria of THIA x 2 d IVE X1 P = Judgement 25 mg x 2/d 200µg/kg Negativation 48/92 60/106 serology Cure rate 52% 56% 0.53 Negativation 35/37 30/5 3 Stool test Cure rate 94% 85% 0.19

Bisoffi Z, et al. PLoS Negl Trop Dis 2011; 5: e1254 Loiasis (Loa loa) Loiasis

Calabar edema

Creeping dermatits

In case of Calabar oedema the diagnosis of loiasis can be confirmed by..

• Microfilaremia • Serology • Blood PCR • Ultrasonography • Histology • PCR on tissue specimen Ultrasonography of the right calf shows a pipeline-shaped lesion Xiaohui Wang et al. J Travel Med 2012, 19: 314-316 Result of surgical excision of Calabar oedema and calf biopsy specimen • No worm was found on examination of this mass • Histopathological examination revealed only inflammatory cell infiltration, mainly eosinophils. • Total DNA was extracted from the calf biopsy specimen and Nested PCR confirmed the dg of loiasis • Calabar swellings are manifestations of localized angioedema related to the subcutaneous migration of L loa Xiaohui Wang et al. J Travel Med 2012, 19: 314-316 You have made the diagnosis of loiasis. You are going to treat this patient with….

• Single dose of ivermectin • Single dose of albendazole • 21 days course of albendazole • 7 days course of diethylcarbamazine • None of them Treatment of loiasis: 4 rules

• Tt in specialized units or by specialized MD • Evaluating microfilaremia density (10 AM- 4 PM) is mandatory before any Tt • DEC & IVE can both induce potentially fatal encephalopathis in persons having microfilaremia > 30-50.000/ml • Definitive cure of loiasis is difficult when DEC (the only drug with macrofilaricidal effect) is not available

Boussinesq M. J Travel Med 2012 Management of loiasis mf/ml Treatment < 2.000 Start with DEC; increase the daily dose everyday up to 400 mg/d 2.000-8.000 Start with ivermectin; wait for 10 days; then use DEC if mf/ml OK 8.000-30.000 Start with albendazole; wait for 6 months; then use DEC or IVE then DEC >30.000 Start with albendazole or plasmapheresis; then use DEC or IVE then DEC

Boussinesq M. J Travel Med 2012 Répartition géographique gnathostomose

JS.Herman,PL.Chiodini.Gnathostomiasis, Another Emerging Imported Disease.Clin.Microbiol.Rev.Jul 2009;22:484-492.

Gnathostomiasis to be suspected in

• A traveller, a migrant • Country of endemicity (SEA…,) • At risk meals (ceviche, lap………,) • Cutaneous signs (+ visceral involv) • Usually with eosinophilia • Dg + : serologic tests, extraction • Tt : albendazole, ivermectin Fasciolasis ( gigantica)

Xuang LT et al. Am J Trop Med Hyg 2005; 72: 508-509 Fasciola gigantica

• Larva of F.gigantica, a trematode • Vietnam • 1 cutaneous trail, slow creeping dermatitis • Duration = 3 weeks • High eosinophilia • Dg + : serology, anatomic • Treatment : triclabendazole

Xuang LT et al. Am J Trop Med Hyg 2005; 72: 508-509 Human scabies (Sarcoptes scabiei) Pyemotes dermatitis (Pyemotes ventricosus) An itchy furoncular like lesion An « itchy » papular skin lesion of the ankle of 4 days duration in a patient returning from Senegal since two days Myiasis = Infection of the human skin by maggots (larvae) of flies (Diptera) that usually infect animals Imported cutaneous myiasis in Western countries

Country France Great Britain Germany Reference Caumes, CID Mc Garry, Lancet Jelinek, IJD

Patients 25 19 13

C. anthropophaga 20 9 6 D. hominis 4 4 6 C. hominivorax 1 1 O. ovis 1 H. lineatum 1 Furoncular myiasis

Diptera Cordylobia Dermatobia anthropophaga hominis

Geography Africa America

Development 9 days 3-6 weeks

Transmission Sand Insect

Localisation Covered areas uncovered areas

Number 1-94* 1-3 Extraction manual surgery

* Biggar et al;Clin Pediatr 1980;19:231-232 (a child from Ghana with 94 lesions)

All these patients have something in common. What is it?

• Place of acquisition • Localisation • Duration of the disease • Clinical aspect • Type of disease • Type of treatment

Key points to think LC leishmaniasis • Return from endemic areas • Exposure to bites by Phlebotomidae • Medium to long incubation period • Localisation on uncovered areas • Absence of pain • Below 10 cutaneous lesions • Failure of antibiotics LCL : pourquoi traiter ?

• AM : pas de complications viscérales ; très rares atteintes CM et CD (L. aethiopica ; ID). • NM : pas de complications viscérales ; fréquence atteintes CM (L. braziliensis…) • 10 % patients initialement • <3% actuellement • Taux guérison stade nasal : 75% • Indication thérapeutique : esthétique! Key drugs to treat LC leishmaniasis • Antimonials IM (NW) or IL (OW) • Pentamidine isethionate (NW; Lg complex) • Fluconazole oral (OW; L.major) • Ketoconazole oral (NW; L.mexicana) • Miltefosine oral (NW; not L.b complex) • Paromomycin Topical (OW) • Heat, 50°C 30 sec (OW; L.tropica) Wortmann G. Clin Infect Dis 2005; 40:1156-1158 Ampho B liposomale c% LCL < 2010

Amato 600 mg Bresil 1/1 Brown 41 mg/kg L.b 1/1 Gunduz 36 mg/kg L.t 0/1 Mirzabeigi 300 mg/kg Bolivie 1/1 Paradisi 21 mg/kg L.i 1/1 Rapp 18 mg/kg Djibouti 1/1 Rongioletti 15 mg/kg L.i 1/1 Rodal 50 mg/kg L.b 2/2 Solomon 18 mg/kg L.b 7/7 Torre… 31 mg/kg Espagne 1/1 Perez… 21 mg/kg L.b 0/2 Ampho B liposomale et LCL

• N = 20 milit. US (10 AM/10 NM) (Lm, Lt / Lb, Lg, Lp) • Ambisome : 3 mg/kg/jr (2 heures) (5-10 doses/pt, J1-5,J14,J21) [dose cumulée = 21 mg/kg (10-30)] • Age : 29 ans ; 95 % M ; nb lesion/pt = 1 (1-11) • 13 patients avec EI (65 %) * toxicité rénale : 9 (45 %) * « infusion related toxicity » : 5 (25 %) • 16/19 pts (84 %) : guérison • 3/19 (16%) : échecs (guéris avec 2nd cure) • Coût = 6500 US $ / cure (median dose)

[Wortmann G et al. Am J Trop Med Hyg 2010;83:1028-1033] LCL : indications thérapeutiques

• Évolution spontanée favorable : Taux de guérison à 3 mois (placebo) : 5 - 75% • Évolution variable selon l’espèce : kétoconazole au Guatemala guérit L. mexicana mais inefficace sur L. braziliensis. • Indications thérapeutiques = parasitologique = géographique The rapid diagnosis of the culprit species (Li, Lm, Lt) in this case of LCL will relie on

• Clinical aspect • Country of acquisition (Tunisia) • Optical microscopy • Serology • Histology • Culture of cutaneous specimen • PCR on cutaneous specimen How determining the culprit species in LCL ? • Clinical presentation may give an orientation but lacks of specificity – Tunisia (Aoun K, 2013); Guatemala (Herwaldt, 1992) • Place of acquisition is reliable for OW species if a) geographic distribution is well known, b) no species overlap, c) single place (Morizot G, 2013) – https://www.parasitologie.univ-montp1.fr/cnrI2.htm – https://www.whp.int/topics/leishmaniasis/fr

Buffet P. Ann Dermatol Venereol 2012; 139: 515-517. Morizot G et al. Clin Infect Dis 2013 The treatment of LCL is preferably ..

• Local/topical in NW AND • Parenteral/oral in OW • Local/topical in OW AND • Parenteral/oral in NW L. major (Afghanistan), IL AM, Miltefosine

• Netherlands 172 MP + 3 non MP (Mazar el Sharif) • Tt with IL AM + cryotherapy in 172 pts : – 141 cured (81 %) – 31 failure (19%) • Oral miltefosine 150 mg/jr x 28 days (31+3 = 34) – 30 cured (88 %) – 4 failure (AM iL, AM iM) • Decrease of ejaculate volume in 21 pts (61 %)

Van Thiel PPAM et al, Clin Inf Dis 2010:50;80-83 Miltefosine vs AM IM, LCL (L. major) Iran

Miltefosine AM Dose 2,5 mg/kg 20 mg/kg Durée 28 jrs 14 jrs Voie PO IM N = 32 31 45 jrs 43 jrs ITT(M3) 81 % 80 % PP(M3) 92 % 83 % Intolérance 9,8 % 41 %

[Mokebeli M et al. Acta Tropica 2007;103:33-40] Topical paromomycin +/- gentamycin vs placebo for LCL in Tunisia (L.major)

Tt for 20 days Paro 15% Paro 15% Vehicule mITT pop Genta 0.5% N = 125 125 125 Cure rate IL 82% 81% 58% Superinfect° 2% 0% 10% AE vesicules 26% 25% 7%

Differences between Tt groups : P < 0.001 vs vehicule

Ben Salah A et al. N Engl J Med 2013; 368: 524-532 Local or systemic Tt for NW LCL ?

• Incidence of ML after LCL: < 3% (except Bolivia) • Severity of ML : not that seen in the past • Efficacy of different treat for ML: good • Toxicity (and cost) of systemic Tt: high • Risk factors for developing ML in LCL : … Local Tt might be considered as a valuable option for travellers with NW LCL

Blum J et al. International Health 2012; and at CISTM 2013 Thursday morning Local or systemic Tt for NW LCL ?

Local Tt might be considered as a valuable option for travellers with NW LCL given that there are no risk factor for developing ML such as… • Multiple lesions • Lesions > 4 cm2 + lymphangite • Head/neck location nodulaire • Immunosupression • Acquisition in the high Andean countries, notably Bolivia

Blum J et al. International Health 2012 Miltefosine vs AM for LCL in Colombia (L.guyanensis, L.panamensis)

Failure rate Meglumine Miltefosine (98%CI) antimoniate IM Oral At Wk 26 20 mg Sb/kg/d 1.8-2.5 mg/kg/d 20 days 28 days N = 58 58 PP pop 28% (14-42) 12.7% (2.3-23) ITT pop 31% (16.9- 45.2) 17% (5-28)

Differences between Tt groups = - 15 % (-1 to 33) PP Rubiano LC et al. J Infect Dis 2012; - 13 % (-4 to 32) ITT (P= 0.04) 205: 684-692 Tt LCL : orienté par la clinique ett l’espèce • Lésions < 1 cm et L. major ou L. mex (guérison spontanée < 6 mois) abstention Tt Tt local : AM IL + cryothérapie • Lésions « cosmétique » ou L. tropica ou L. braziliensis (potentiel métastatique, pas de guérison spontanée) AM IM ou Ambisome (3mg/kg à J1 - J5, J14, J21 = 20 mg/kg dose cumulée)

[Wortmann G et al. Am J Trop Med Hyg 2010;83:1028-1033] Pruritic skin lesions

Pruritus

Localized Generalized

sine materia withskin lesions Generalized pruritus

• Scabies • Ciguatera • Cercarial dermatitis • Marine dermatitis • Filariasis (, loiasis) • Invasive phase of helminthic disease • PUO (aged African migrants VFRs) Courtesy Antoine Mahé

Courtesy Antoine Mahé (Colmar, France) Scabies = Pruritus

• Occurs within one month after exposure (1st episode) and within a few days (history of previous scabies) • Generalized and intense itching, worsening at night, usually sparing the face and head • Specific findings : 5 to 10 mm burrows, vesiculopustules and papulonodular genital lesions. Classic distribution : interdigital web spaces, flexor surfaces of the wrists, elbows, axillae, buttocks, genitalia and breast. • Microscopic diagnosis : identification of female mite, eggs, or fecal pellets. Itching in the marital bed is scabies Common scabies = treatment

• Varies according to the country • Local: either permethrin OR benzyl benzoate • Oral : ivermectin • To be repeated : – D2 for BB, – D7 for permethrin, – D 14 (D 7) for ivermectin • Also include persons sharing the same household – Sex/bed partners – children Tt scabies in Dakar : Ivermectin (1 dose) vs BB (1 application) vs BB (2 applications)

Patients Cured D 14 Cured D 28 N = 181 86 126 BB 1 68 37 (54%) 52 (76%) BB 2 48 33 (68%) 46 (95%) IVER 65 16 (24%) 28 (43%)

OR = 2 (0.9-4.6) BB2 vs BB1, Ly F et al. Bull WHO = 0.2 (0.1-0.5) IVE vs BB1 2009; 87 : 424-430. Prurit localisé au retour de voyages

• Arthropode induit : – prurigo aigu [sur place (73 %), histoire de piqûres d’insecte (47 %), jambes (78 %)], – prurigo bulleux, – « papular urticaria » • Prurit d’acclimatement (immigrés d’origine africaine, personnes + agées)

Caumes E et al. Clin Inf Dis 1995; 20 : 542-548 Ansart S et al. Am J Trop Med Hyg 2007; 76 : 184-186

Dermatoses marines

. Dermatite cercarienne . Dermatite des nageurs . Envenimations marines Blessures vulnérantes Blessures avec envenimation Contact avec envenimation

Tropical skin diseases in travellers • Top : hookworm-related cutaneous larva migrans (to be distinguished from the other causes of creeping dermatitis), localized cutaneous leishmaniasis (old world and new world), tungiasis and myiasis (mainly furoncular forms). • Other exotic dermatoses such as M.ulcerans infection (Buruli ulcer), cutaneous anthrax, cutaneous and amebiasis are exceptionally observed in this setting. Etiologies Exanthème fébrile chez 62 voyageurs au retour

Virus Chikungunya (35%), dengue (26%), EBV (5%), HIV (3%), CMV (2%), Rougeole, Rubeole et varicelle (2%) Bacteria Fièvre Africaine à tiques (10%), Toxic Strep syndrome (2%) Parasite Toxoplasmose, bilharziose aigue (2%) ADR Nevirapine (traitement prophylactique post exposition en Afrique (2%) Unknown 8%

Hochedez P et al. Am J Trop Med Hyg 2008; 78:710-713

Dengue fever

Dengue vs Chikungunya

Variable Chikungunya Dengue P = N = 22 N = 16 Arthralgies 100% 0% <0.001 Prurit 48% 31% NS Neutropenie 10% 81% <0.001 Thrombopenie 35% 88% 0.002 Cytolyse hépatique 65% 88% NS

Hochedez P et al. Am J Trop Med Hyg 2008; 78:710-713 Chikungunya

Courtesy P.Hochedez Chikungunya chez 157 patients, Réunion

• Age : 57 ans, M/F = 1.2; comorbidité chez 60% • Hospitalisation : 61% • Polyarthralgies : 96% • Fièvre : 89% • Signes GI : 47% • Exanthème : 40% (prurit: 54%; bulles: 4.8%) • Signes neurologiques : 12% • Signes hémorragiques : 6%

Borgherini G et al. Clin Inf Dis 2007; 44 : 1401-1407

West Nile, New-York, 08-09/1999, 59 pts

• Encéphalite: 37 (63%) • Méningite: 17 (29%) • Fièvre: 53 (90%) • Asthénie: 33 (56%) • Nausée: 31 (53%) • Diarrhée: 16 (27%) • Exanthème: 11 (19% )

Nash D et al; N Engl J Med 2001; 344: 1807-18014 West Nile dans le Var • Eté 2003 • Hopital de Fréjus Saint Raphael • 4 cas: 2 méningoencéphalites, 2 syndrome pseudo grippal associés à un exanthème • Exanthème, macules erythémateuse (roseole like), tronc, paumes, plantes épargnées, conjonctivite; prévalence: 5- 25 % selon épidémies

Del Giudice P et al. Emerging Infectious Dis 2004; 21 : 65 - 67

Rougeole : maladie ré-emergente Rougeole de l’adulte : maladie émergente

• Importance de la couverture vaccinale à l’âge scolaire • Intérêt du rattrapage vaccinal chez les adultes non vaccinés, particulièrement les professions médicales et paramédicales • Vaccin lors de séjours en pays « importateurs » de rougeole. Epidémie de rougeole, France 2008-2012 = 22.178 cas notifiés 16000 14000 M/F ratio = 1.05 12000 3 vagues successives, D5 puis D4 Incidence : 2.7 à 25.6/100.000 hbts 10000 Median age= 12 ans (IQR = 5-18) à 16 ans (IQR = 7-24) 8000 N = 6000 4000 2000 0 2006 2007 2008 2009 2010 2011 2012

Antona D et al. Emerg Inf Dis 2013; 19: 357-364 Epidémie de rougeole, France 2008-2012 = 22.178 cas notifiés • Statut vaccinal (n=6841): 1375 + (20%) [1041 (15%) 1 dose, 318 (4.7%) 2 doses] • Complications (plus fréquentes chez l’adulte) : 2582 (11%), pneumonie (6%), OMA (1.4%), hépatite/pancréatite (1%), myélite (n=1), encéphalite (26 dont 25 ADEM) • Hospitalisation: 4980 (22%) • Décès: 10 (0.45 mort/1000 cas)

Antona D et al. Emerg Inf Dis 2013; 19: 357-364

Meningococcemia Typhoid fever (rose spots) Febrile exanthema may be caused by • Arboviruses : dengue, West Nile, Chikungunya, … • Bacteria : Rickettsia sp, S.pyogenes, S.aureus, M.meningitidis,… • Parasites : helminthic infections (urticaria), toxoplasmosis, trypanosomiasis • Drugs, i.e., adverse cutaneous reactions Urticaire aiguë

Helminthiases (PE) - en phase invasive : ascaris, Epidémiologie (contamination) ankylostomose, anguillulose, Clinique distomatoses, bilharzioses Serodiagnostics hydatidose fissuraire Ex parasitologique direct < 0 - en impasse parasitaire : Tt d ’épreuve antiparasitaire gnathostomose, anisakiase, toxocarose, trichinose Invasive schistosomiasis (acute urticaria) Acute schistosomiasis in 14* travellers in Mali (S.haematobium), Signs % Interval/exposure Duration (d) Fever 93 19 d (15-24) 9 (2-30) Urticaria 57 33 d (21-55) 4 (1-8) Cough 86 30 d (18-65) 61 ( 7-210) Eosino 100 47 d (25-119) 113 (1-190) Seroconversion 100 46 d (27-100) NA

Ova in urines 57 196 d (124-330) NA

* : 10 treated, Grandière-Perez L et al. Am J Trop Med Hyg 2006; 74: 814-818 4 worsened Subungueal splinter hemorrhages in a 21 y old tourist with acute schistosomiasis (S.haematobium in urines, 4 months later), 1 month after bathing in a cascade in the Dogon area (Mali), and 2 days after PRZ treatment for acute schistosomiasis Acute neuroschistosomiasis

Magnetic resonance imaging (T2 flair) showing borderzone infarcts suggestive of cerebral vasculitis in a 21 y old tourist with acute schistosmiasis (S.haematobium), 1 month after bathing in a cascade in the Dogon area (Mali), 2 days after PRZ treatment Cutaneous signs may reveal systemic tropical diseases • Gnathostomiasis (creeping dermatitis, panniculitis, limb oedema), • African trypanososomiasis (trypanoma, trypanids), • American trypanosomiasis (chagoma), • Filariasis (loiasis, onchocerciasis, ), • invasive helminthic diseases (urticaria, subungueal hemorrages), • Rickettsial infections (febrile exanthema more or less inoculation escar) • Arboviral infections (febrile exanthema). Le voyage est associé à une perte des inhibitions naturelles…… STD are a common (underestimated) cause of health impairment in travellers

731 British travellers (1) 5.7 % 622 French travellers (2) 3.7 % (6th) 121 Swiss VFRs (3) 1.6% 217 Swiss travellers (3) 0.3% 17353 WW travellers (4) 0.8 % 7886 Swiss travellers (5) 0.6 % genital discharge (7th) 0.1 % genital ulcer (11 th)

(1) Hawkes S et al. AIDS 1994;8:247-252 (2) Ansart S et al. J Travel Med 2005. 12:312-318 (3) Fenner L et al. Emerg Infect Dis 2007;13: 217-222 (4) Freedman D et al. N Engl J Med 2006; 354:119-130 (5) Steffen R et al. J Infect Dis 1987; 156:84-91 61 patients avec une MST présumée acquise pendant un voyage (1990s)

• HPV “primary infection” (32%) • Uretrite non gonococcique (31%) • Gonococcie (8.2%) • Trichomonose vaginale (6.5%) • Herpes génital (6.5%) Moyenne de 3 mois entre le retour et la consultation

Hawkes S et al. Genitourin Med 1995; 71: 351-4 49 voyageurs français (22 F, 37 M) avec MST, 11/2002 - 10/2003

• Uretrite gonococcique (n=18, 4 avec resistance aux FQ)(hommes seulement, p<0.001) • HSV 2 (n=12)(oral et génital) Moyenne de • Urethrite d’étiologie indéterminée (n=9) 9 jours • Chlamydia trachomatis (n=4) entre retour • Syphilis, primaire (n=4)(MSM) et consult • Primo infectionVIH (n=2)(1F,1M). [Candidose vaginale (n=10)] Ansart S et al. J Travel Med 2009; 16: 79-83 Man, 45 y Coming back from Bangkok

…….in exotic (migrants) persons (n=51, 24%)

1. Prurit of unknown origin : n=13; 25% 2. Filariasis (loiasis, onchocerciasis): n=8; 15% 3. Infectious cellulitis: n=6; 11% 4. Scabies: n=4; 7,8% 5. Leprosy: n=4; 7,8% 210 migrants; 11/2002 – 5/2003 6. Tungiasis: n=3; 5,8% Mean Age : 37 (18-63) 7. Pyoderma: n=2; 4% African origin : 89% 8. Myiasis, n=2; 4% Lag time/return : 23 days (1-90) 9. Tinea, n=2; 4% 10.Herpes, zoster, n=2; 4% 11.Contact dermatitis, n=2; 4% Ansart S et al. Am J Trop Med Hyg 2007; 76 : 184-186 12.Others, n=3 Main causes of skin consultations in migrants

• Pruritus (xerosis….) • Pigmentary disorders (hypopigmentation and hyperpigmentation) • Hair problems (traumatic alopecia, pomade acne, hair shaft abnormalities, pseudo folliculitis barbae…) • SSTI, again and again…. • A few (less and less) exotic diseases : leprosy, loiasis, myiasis, LCL, HrCLM, gnathostomiasis…. Main problems faced by Western dermatologists seing migrants

• Where is the erythema ? • Rule out leprosy when facing hypopigmentation • Deal with hyperperpigmentation and skin sequellae • Treat hair and follicular problems • Do with end stage disease Dépigmentants en Afrique

• Prévalence importante • Sénégal (Dakar) : 67% • Mali (Bamako) : 25% • Femmes jeunes, urbaines et actives • Dermocorticoides et hydroquinones • Complications cutanées • Complications viscérales (freinage de l’axe hypothalamo hypophysaire, HTA, diabète) « Raissal » (blanchiement de la peau) à Dakar

425 utilisatrices de « blanchissants »

Substance active Nb d’utilisatrice (%) Hydroquinone 378 (89 %) Corticoides 297 (70 %) Mercuriels 43 (10 %) Agent caustiques 72 (17 %) Inconnu 55 (13 %)

(Mahe et al. Br J Dermatol 2003;148:493-500) Inapropriate use of corticosteroids based ointment for lichen simplex chronicus lead to depigmentation of the skin area surrounding the lesion Dermatoses observées chez 425 utilisatrices dépigmentant à Dakar

Dermatoses Nb ptes (%)

Dermatophytie 128 (30 %) Gale 69 (15 %) Acné 123 (29 %) Hyperchromie 154 (36 %) Vergetures 169 (40 %) Hypertrichose 43 (10 %) Eczéma 43 (10 %)

(Mahe et al. Br J Dermatol 2003;148:493-500) Courtesy : Antoine Mahé, Colmar, France

Ochronosis : Complications due to hydroquinone Carcinomes épidermoïdes

Courtesy : Antoine Mahé, Meaux, France Bleaching during pregancy in Dakar, Senegal

• 01/2003-06/2003; Maternity Unit of the institut d’hygiène sociale, Dakar; women randomly selected • 99 pregant women included, mean age : 25 (15-42), mean parity : 1.3 (0-8) • 68/99 (68%) used lightening products for cosmetic purpose. Actives principles : hydroquinone (64/68), steroids (34/68, including highly potent steroids use in 28/34), caustics (2/68); •Products were applied to the whole body in 58 cases at least once a day; for a mean period of 5 years (3 months- 24 years) Mahé A et al. Tr R Soc Trop Med Hyg 2007; 101 : 183-7. Bleaching during pregancy in Dakar, Senegal

Variable Use of highly No use of HP P potent corticoster corticosteroids Vaginal bleeding 5/28 (18%) 2/60 (3%) 0.03 Placental weight 565 gr 632 gr 0.04 New born weight 7/23 (30%) 6/56 (11%) 0.04 < 2.5 kgs Plasma cortisol 652 nM/L 738 nM/L 0.007

Highly potent corticosteroids users = 28 pregant women (mean : 60 gr/month)

Mahé A et al. Tr R Soc Trop Med Hyg 2007; 101 : 183-7. Cutaneous diseases in returning travellers • Acquisition: arthropods bites • Warning: bacterial infections • Imported < 1/3 cutaneous disorders • Types of dermatoses most strongly related to: time of onset / return (incubation period), traveler status (migrants tourists), country visited. Merci pour votre attention

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