Perianal infectious dermatitis: An underdiagnosed, unremitting and stubborn condition

Table 1 Studies/case series with perianal infectious dermatitis: Clinical and bacteriological patient characteristics

Name, yr, country, study design	Population size; age; sex	Symptoms/signs1;symptom duration	Etiologyof PID	Otherfindings2
Amren, 1966, United States, PS[2]	10; 1-8 yr, half < 5 yr; 90% M	Painful defecation, constipation, anal pruritus, perianal pain, mucoid or bloody anal discharge; 1 F also with vulvo-vaginitis	GAS (culture)	Throat GAS positive: 28% (no symptoms)
Spear, 1985, United States, RS[28]	14; mean age 3.9 yr (1-10 yr); 11 M	Painful defecation (14), constipation (6), bloody stool (7), anal fissure (5); mean duration: 6.2 mo (range: 1-12 mo)	GAS (culture)
Kokx, 1987, United States, RS[4]	31; 7 mo to 8 yr (mean 4.25 ± 1.8 yr); 77% M	Perianal itching (78%), rectal pain (52%), and blood-streaked stool (35%)	GAS and RADT	Throat GAS positive: 64%; identical perianal and pharyngeal T-type (T28, 5 cases; T4, 4; T2, 1)
Krol, 1990, Canada, RS[20]	8; 8 mo to 10 yr; 6 M	Perianal pruritus (8); painful defecation (4); anal fissure (2); bloody stool (1); 3 wk to 6 mo	GAS (culture)
Grant, 1993, United Kingdom, RS[10]	20; 5 mo to 12 yr (mean 5 yr); 75% M	Perianal discomfort (14) and itch (13), fresh blood per rectum (12), pain on defecation (10), perianal pain (4), anal mucus discharge (2); 3 wk to 1 yr (mean 3 mo)	GAS (culture)
Patrizi, 1994, Italy, RS[22]	1. 10 yr, M	1. Pruritus, tenesmus, constipation, acute GP and mild balanitis	GAS (culture)	1. Throat GAS negative; penile GAS: same antibiogram
	2. 4 yr, F	2. Anal pruritus, vulvar and perineal erythema, and GP; 4 mo		2. Throat GAS negative
	3. 5 yr, F	3. PID and GP		3. Throat GAS positive
	4. 9 yr, M	4. Painful defecation, GP; 1 mo		4. Throat GAS positive
	5. 7 yr, M	5. PID and balanitis		5. GAS tonsillitis 3 mo before; penile GAS and mother with cervical GAS (child and mother bathing together)
Wright, Australia, 1994, PS[11]	22; 5 mo to 8 yr (mean 41 mo); 13 M	Painful defecation, bleeding ± anal pain, perianal pruritus, constipation	Culture: 12 GAS, 1 GBS, 1 GCS
Mostafa, 1997, Egypt, PS[15]	150; 2 mo to 11 yr (mean 3.8 ± 2.1 yr); 75% M	Perianal itching (15%), gastroenteritis (34%)	BHS: 35.3%, S. aureus 3.4%	Throat: BHS 44% (GAS 21.3%, non-GAS 22.7%); PID caused by GAS: 53.8% with same GAS in the throat
Barzilai, 1998, Israel, PS[14]	18; 7 mo to 5.4 yr; 10 M	Perianal pruritus (50%); painful defecation or constipation (44%); anal fissure (39%); purulent secretion (27%); rectal bleeding (16%); 2 GP	GAS	GAS in other locations: 72%; 4 siblings throat GAS positive (no symptoms)
Mogielnicki, 2000, United States, RS[5]	23; mean age 5 yr (1-11 yr); 13 F	13 only PID; 2 PID + vulvo-vaginitis; 8 only vulvo-vaginitis	GAS (culture)	Throat GAS positive: 92% (± symptoms)
Mateo, 2002, Spain, RS[19]	10; 9 mo to 7 yr; 6 M	Oozing and rectal bleeding, anal pruritus, pain on defecation; 1 M also GP; 20 d to 2 yr	GAS	Throat GAS positive: 3/6
Petersen, 2003, Denmark, RS[27]	17; mean age 6 yr (3-13 yr)	Painful defecation, fresh blood on stool	GAS 12 (11 M) T28	Throat GAS positive 12%; 6/12 with T28 from kindergarten
Landolt, 2005, Switzerland, RS[17]	13; 7 F	Obstipation (58%), painful defecation (50%), perianal itching (25%), melena (25%); 10 cases with > 1 symptom	GAS positive in 12
Echeverría Fernández, 2006, Spain, PS[6]	19; 6 mo to 4 yr (median age 12 mo)	Anal pruritus (19), constipation (9), anal fissures (5), rectal bleeding (4), vulvo-vaginitis (2)	GAS (RADT and culture)	Throat GAS positive: 80%; GAS pharyngitis: 1 case
Meury, 2008, Switzerland, RCT[12]	35; 1-16 yr	Either typical erythema or at least 2 of: perianal itching, rectal pain, painful defecation, constipation, blood-streaked stool, rectal mucopurulent discharge, or anal fissure	GAS
Jongen, 2008, Germany, RS[8]	21; < 14 yr (mean age 6.3 yr); 76% M	Perianal itching, sore anus, bleeding and pain at defecation; mean duration of 6.6 months (2 wk to 2 yr)	17 GAS, 4 (culture)
Shouval, 2008, Israel, RS[18]	11; 6 mo to 4 yr (mean 24 mo); 73% M	Irritability (all), perianal itching (6) and pain (3); < 28 d	GAS (RADT)
Heath, 2009, United States, RS[26]	26; 5 mo to 12 yr; 15 F	Anal erythema or recurrent buttocks dermatitis; in PID caused by S. aureus: specific small papules and pustules of the buttocks or extension of the erythema to adjacent buttock skin	S. aureus 82%, GAS, GBS
Olson, 2011, United States, RS[25]	81; mean age, M: 4.1 yr and F: 4.6 yr; 58% M	(86.4%) perianal involvement; (22.2%) symptoms for at least 2 wk (6.2% with symptoms for at least 4 wk); the rest: duration < 1 wk	GAS
Clegg, 2015, United States, RS[23]	157; 18 d to 12.5 yr, mean 4.8 yr, 53% M	Predominant site of involvement: M: perianal (86%) and F: perivaginal area (62%); 9.8 d	GAS	Throat GAS positive: 95%; 100% concordance between perineal and pharyngeal GAS
Cohen, 2015, France, PS[16]	132; mean age 46.6 ± 23.5 mo; 64% M	Painful defecation, anal fissure, bloody stools; 4 also vulvo-vaginitis; 2 wk	GAS (RADT and culture)
Garcia, 2015, Spain, RS[21]	6; 9 mo to 5 yr (mean age 3 yr); 5 M	Perianal rash (6), rectal pain (3), itching (2), vaginitis (1)	GAS	GAS pharyngitis: 30%
Sterbenc, 2016, Slovenia, RS[24]	89 cases < 15 yr (84.7%); median age 5 yr		GAS, GBS, GCS, GGS

¹Besides typical perianal erythema;

²Especially throat culture and infections in the family/community. AB: Antibiotic; BHS: Beta-hemolytic streptococci; F: Female; GAS: Group A beta-hemolytic streptococci; GBS: Group B beta-hemolytic streptococci; GCS: Group C beta-hemolytic streptococci; GP: Guttate psoriasis; M: Male; Pen: Penicillin; PID: Perianal infectious dermatitis; PS: Prospective study; RADT: Rapid antigen detection test; RCT: Randomized controlled trial; RS: Retrospective study; S. aureus: Staphylococcus aureus; T2: T-type 2 of GAS; T28: T-type 28 of GAS; T4: T-type 4 of GAS.

Table 2 Studies/case series with perianal infectious dermatitis: Therapy and follow-up of patients

Name, yr, country	Therapy of PID and results	Follow-up of PID
Amren, 1966, United States[2]	IM Pen, 10 d plus oral Pen, 10 d: disappearance of symptoms in 2-3 d	After therapy: 2 cases GAS positive; 10 d of Pen (same type): Effective in eradicating GAS in both cases
Spear, 1985, United States[28]	Oral Pen: rapid resolution of PID	Recurrence of infection: Not uncommon, requiring a repeated course of oral AB
Kokx, 1987, United States[4]	Oral Pen or amoxicillin, 10 d: clinical and bacteriological clearance in 61%	39% relapses, treated with IM or oral Pen; 4 children failed; 3 successfully treated with oral clindamycin, 10 d; 4th case successfully treated with oral Pen (10 d) and rifampin (last 4 d)
Krol, 1990, Canada[20]	Oral Pen, 10 d plus topical mupirocin in 4 cases (these 4 without recurrence)	2 cases: 2nd course of therapy within 1 mo
Grant, 1993, United Kingdom[10]	Oral Pen, 3 wk: 14 responded (6 plus topical fucidin)	6 cases: No complete response; successful 2nd course of oral Pen and topical fucidin
Patrizi, 1994, Italy[22]	1. Oral erythromycin, 14 d	1. 4 wk later, GP and PID disappeared and all swabs negative
	2. Oral Pen, 2 wk	2. Lesions improved, but swab positive: erythromycin, 2 wk: complete healing (including negative GAS)
	3. Oral erythromycin, 2 wk	3. Lesions disappeared in maximum 5 wk
	4. Oral erythromycin and topical mupirocin, 2 wk	4. 4 wk later, lesions and culture negative
	5. Amoxicillin, 2 wk: good results	5. 4 wk later, perianal GAS, no lesions; 2nd course of amoxicillin: good results
Wright, Australia, 1994[11]	Oral amoxicillin - clavulanate plus topical bacitracin, 2 wk	50%: Response to treatment in 2 wk; no recurrence
Barzilai, 1998, Israel[14]	Oral amoxicillin, 10 d and topical mupirocin: 16 patients clinically cured; perianal cultures GAS negative: days 3-5 of therapy and weeks 2 to 3 post-therapy	Recurrence: 2 cases (clinical and culture); successfully retreated 1 wk after finishing first therapy
Mateo, 2002, Spain[19]	IM Pen (1), oral amoxicillin (5), topical mupirocin (4)	All with favorable response and no recurrence
Petersen, 2003, Denmark[27]	Oral Pen, 10 d: ineffective in 3 cases	3 cases: Clarithromycin, 7 d; no recurrence
Landolt, 2005, Switzerland[17]	10 with > 1 symptom: oral Pen, 10 d; 3: oral or IV amoxicillin-clavulanate	4 with persistent symptoms: 2nd course of AB - oral Pen (3 cases), 14 d and oral clarithromycin (1 case), 10 d; 1 mo later: all 4 healed
Echeverría Fernández, 2006, Spain[6]	Oral Pen, 10 d	Favorable in 85%, perianal GAS negative in 95%
Meury, 2008, Switzerland[12]	15 cases: oral Pen, 10 d and 14 cases: oral cefuroxime, 7 d	Clinical improvement: More rapid in the cefuroxime group (P = 0.028) and perianal GAS negative the last day of therapy in 93% on cefuroxime vs 47% on Pen (P < 0.01)
Jongen, 2008, Germany[8]	Oral Pen ± local polihexanid, 10-14 d	1 case: New GAS associated PID 5 mo later; successfully treated with oral AB
Shouval, 2008, Israel[18]	Oral amoxicillin, 10 d and topical mupirocin (8/11); complete healing in 73%	Recurrence: 3/11; 2nd course of AB administered
Heath, 2009, United States[26]	Oral cephalexin for S. aureus: Successful in all but one; 4 cases with S. aureus cleared on topical mupirocin and 1 on bleach baths and topical steroids	1 case with MRSA: 2nd course of oral AB required
Olson, 2011, United States[25]	Oral AB alone: 81.4%; topical agent alone: 2.5%; both: 16%; duration: oral beta-lactams 10 d, azithromycin 5 d, cephalexin 5 d, oral Pen 14 d	Recurrence 32.1%; recurrence within 6 wk 69.2%; recurrence rate: After Pen or amoxicillin 38.1% vs 27.8% after a beta-lactamase resistant AB (adjusted odds ratio: 2.02)
Clegg, 2015, United States[23]	Amoxicillin 82.2%; cephalexin 11%; other AB 7%; topical therapy: 6%	Recurrence rate (symptomatic PID) 6 mo after the initial episode: 13.4% after any AB, 12.4% after amoxicillin, 29.4% after cephalexin, and 0% after all other AB (oral Pen, amoxicillin-clavulanate, azithromycin, clarithromycin, cefprozil and cefdinir)
Garcia, 2015, Spain[21]	Oral AB (Pen 5, amoxicillin 1), plus 4 topical mupirocin and 3 clotrimazole	Satisfactory; 1 recurrence
Sterbenc, 2016, Slovenia[24]		All BHS: susceptible to Pen; all GAS susceptible to clindamycin, 1.4% resistant to erythromycin; GBS resistant to erythromycin in 14.8% and clindamycin in 7.4% of cases

AB: Antibiotic; BHS: Beta-hemolytic streptococci; GAS: Group A beta-hemolytic streptococci; GBS: Group B beta-hemolytic streptococci; GP: Guttate psoriasis; IM: Intramuscular; IV: Intravenous; Pen: Penicillin; MRSA: Methicillin-resistant S. aureus; PID: Perianal infectious dermatitis.

Table 3 Case reports with perianal infectious dermatitis: Clinical and bacteriological patient characteristics

Name, yr, country	Case age, sex	Symptoms/signs1; symptom duration	Etiology of PID	Other findings2
Hirschfeld, 1970, United States[59]	1-2. 6 yr, F and 3 yr brother	1-2. Painful defecation; several days	GAS (culture)	1-2. Both had sore throats 2 wk prior
	3-4. 5 yr and 3 yr brothers (unrelated family)	3-4. Same history and symptoms		3-4. Throat GAS positive (1 case)
Farmer, 1987, United Kingdom[65]	1. 4 yr, M	1. White anal discharge, perianal pustules; 3 wk	GAS (culture)
	2. 5 yr, F	2. Perianal itching, pain on defecation, dysuria; vulva affected; 3 wk
Rehder, 1998, United States[61]	1. 3 yr, M	1. Rectal irritation; 6 mo	GAS (culture)	1. Sibling, 6 yr: GAS pharyngitis recently
	2. 3 yr, M	2. Perianal pain and itching; 5 wk		2. Patient: throat GAS positive; sibling with recent sore throat
	3. 4 yr, M	3. Perirectal pain; 6 wk		3. Identical GAS from anus and throat
	4. 1 yr, F	4. GP; 3 wk
Honig, 1988, United States[62]	4; 15 mo, 6, 8 and 12 yr; 3 M	Anal pruritus, bloody anal discharge; GP: 2 cases, appeared 9 mo after onset of PID; 1 M with PID history of 2 yr	GAS (culture)
Marks, 1988, United States[63]	5 yr, M	Perianal irritation and pruritus, bloody discharge; 2 wk	GAS (culture)
Guerrero - Vázquez 1989, Spain[64]	2 cases	Perianal irritation in both; seropurulent anal and balano-preputial discharge in 1 case	GAS (culture)
Duhra, 1990, United Kingdom[29]	5 yr, M	Painful defecation, micturition, bloody stool; penile erythema swelling; 4 wk	GAS (culture)	GAS positive from penile skin; members of patient's family: severe sore throat recently
Goodyear, 1991, United Kingdom[30]	4 yr, M	Painful defecation, blood-streaked liquid stool; fecal incontinence; 6 wk	GAS (culture)
Medina, 1992, Spain,[31]	4 yr, M	Perianal pruritus and bleeding; 3 mo	GAS (culture)
Montemarano, 1993, United States[32]	3 yr, M	Painful perianal area, satellite pustules; 2 mo	S. aureus (culture)	S. aureus positive in anterior nares and satellite pustule
Guppy, 1993, Australia[33]	1. 7 yr, M	1. Perianal excoriation; 8 wk	GAS (culture)	The three siblings bathing together
	2-3. His 2 brothers, 5 and 2.5 yr	2-3. Similar history
	4. 4 yr, M	4. Typical PID; penis lesions later; 4 wk
Paradisi, 1993, Italy[34]	3 yr, M	Perianal itching; 2 mo	GAS (culture)
Paradisi, 1994, Italy[35]	1. 3 yr, F 2. 5 ½ yr, M, brother	Painful defecation, perianal itching, rectal bleeding, constipation	GAS
van Zeijl, 1996, Netherlands[36]	4; 3 M (1, 6 and 8 yr, the last 2 brothers); 1 F (2 yr)	Constipation, painful defecation, diarrhea	GAS (culture)	Brothers shared same toilet
Saxen, 1997, Finland[37]	1. 3 yr, M	1. Itchy anus and bloody stool; 1 w	GAS (T28)
	2-3. Other cases	2. Same symptoms		2. Throat GAS positive, identical (T28)
Berlin, 1997, United States[38]	3 yr, M	Constipation, myositis	GAS (culture)	His mother had sore throat GAS positive
Bugatti, 1998, Italy[39]	12 yr, M	Perianal discharge, 1 mo	GAS (culture)
Adams, 1999, Canada[40]	1 yr, M	Typical PID	GAS (culture)
Roos, 1999, Sweden[41]	5 yr, M	Anal pruritus	GAS T28 (culture)	Case: throat GAS negative; mother: GAS tonsillitis positive; anal and throat GAS identical
Velez, 1999, Spain[42]	2 yr, M	Fever 39-40 °C, erythema: perianal, genitalia and proximal thighs	GAS (culture)	Throat negative
Herbst, 2000, Germany[9]	4 yr, M	GP; 6 w history; PID discovered at physical exam	GAS (culture)	Patient and family members: Negative GAS throat
Brilliant, 2000, United States[43]	1. 4 yr, M	1. Rectal itching and pain, scant mucoid discharge	GAS (RADT + culture)
	2-3. 2 mo and 30 mo	2-3. Several days later with similar symptoms		2-3. Siblings of case 1
	4. 4 yr, F	4. Plus vulvitis		4. Neighbor of the 3 cases
Balasubramanian, 2000, India[44]	1. 13 mo, M	1. Fever, painful defecation, anal pruritus; 2 d	GAS (culture)
	2. 11 mo, M	2-3. Fever, painful defecation
	3. 13 mo, F
Heidelberger, Germany, 2000[45]	1. 6 yr, M	1. Anal itching and burning; 3 mo	GAS (culture)
	2. 9 yr, M	2. Balanitis and impetigo
Nowicki, 2000, United States[46]	7 yr, M	Perianal itching, painful defecation; 10 d	GAS (culture)	Throat GAS negative
Soulliet, 2000, France[13]	7 yr, F	Vulvar erythema, perirectal pain, painful defecation, constipation; perioral impetigo; 3 wk	GAS (culture)	Perioral GAS positive
Lunghi, 2001, Italy[47]	Brother (4 yr) and sister (6 yr)	1 also vulvo-vaginitis; 4 mo	GAS (culture)	Throat GAS positive in both patients
Romano, 2002, Italy[48]	12 yr, M	PID and GP	GAS
Huang, 2003, Taiwan[49]	6 yr, M	Perianal itching, painful defecation, scant mucoid discharge	GAS (culture)	Throat GAS positive
Reimer, 2004, Sweden[50]	1. 4 yr, M	1. Perianal discomfort	1. GAS (RADT)
	2. 6 yr, M	2. Purulent discharge plus balanitis	2. GAS	2. Penis culture GAS positive; father treated for GAS pharyngitis; brother, 4 yr with GAS PID and brother 2 yr with GAS pharyngitis
	3. 4 yr, F	3. Perianal pain, vulvar erythema and pain	3. GAS
Takeshita, 2006, Japan[51]	1. 2 yr, F	1. PID; 2 wk	GAS (culture)
	2. 6 mo, M	2. PID; 1 wk
Usuki, 2006, Japan[52]	5 yr, F	PID	GAS (RADT)	4 d later: Father with symptoms of PID and GAS positive
Ulger, 2007, Turkey[53]	3 yr, M	Pain on defecation, anal pruritus; 8 d; GP: 2 d	GAS (culture)	Sore throat 2 wk before; no culture, no therapy needed
Greisser, 2008, Swiss[54]	7 yr, M	Perianal pain and pruritus, yellow discharge; 3 d	GAS (RADT + culture)	Throat GAS negative
Lehman, 2009, United Kingdom[7]	3 yr, F	Itchy bottom and painful defecation; 2 wk	GAS (culture)
Ledoux, 2009, France[55]	4 yr, M	PID for 2 wk; lesions of GP since second week	GAS (culture)
Rasi, 2009, Iran[56]	4 yr, M	Rectal itching and burning, pain on defecation; plaque type psoriasis; 3 mo	GAS (RADT)
Block, 2013, United States[57]	1. 2 mo, F	1. PID and vulvar erythema	GAS	1. 8 yr sibling: previous GAS pharyngitis
	2. 4 mo, F	2. Blood in diaper
Theotokatou, 2014, Greece[58]	1. 8 yr, M	1. Perianal itching, constipation, blood-streaked stool; 3 wk	Enterococcus faecalis (culture) in both)
	2. 10 yr, M, brother	2. Perianal itching and mucous discharge (2 wk after onset of symptoms of his brother)
Zhang 2016, Canada[3]	1. 4 yr, M	1. Painful defecation, GP, penile erythema	1. GAS and S. aureus	1. Throat GAS positive
	2. 4 yr, M	2. Painful defecation, GP	2. GBS	2. Throat culture negative
	3. 3 yr, F	3. Perivulvar erythema, small amount of greenish-yellowish vaginal discharge	3. GCS	3. Throat culture negative; vulvar culture few GCS and scant S. aureus
Garritsen, 2017, Netherlands[60]	19 mo, M	PID and 1 wk later: GP	GAS
Serban, present study, Romania	1. 9 yr 4 mo, M	1. Perianal pain and pruritus, anal mucous and bloody discharge, painful defecation; 6 wk	1. GBS and S. aureus (culture)	1. Throat GAS, GBS and S. aureus negative
	2. 9 yr 6 mo, M	2. Anal pruritus, painful defecation, anal mucous and bloody discharge	2. GAS (culture)	2. Throat GAS positive
	3. 11 yr 9 mo, M	3. Anal pruritus, mucous and bloody discharge, painful defecation, constipation	3. GAS (culture)	3. Throat GAS negative

¹Besides typical perianal erythema;

²Especially throat culture and infections in the family/community. F: Female; GAS: Group A beta-hemolytic streptococci; GBS: Group B beta-hemolytic streptococci; GCS: Group C beta-hemolytic streptococci; GP: Guttate psoriasis; M: Male; PID: Perianal infectious dermatitis; RADT: Rapid antigen detection test; S. aureus: Staphylococcus aureus; T28: T-type 28 of GAS.

Table 4 Case reports with perianal infectious dermatitis: Therapy and follow-up of patients

Name, yr, country	Case age, sex	Therapy of PID and results	Follow-up of PID
Hirschfeld, 1970, United States[59]	1-2. 6 yr, F and 3 yr brother	Oral Pen
	3-4. 5 yr and 3 yr brothers (unrelated family)
Farmer, 1987, United Kingdom[65]	1. 4 yr, M	1. Oral Pen: prompt and complete recovery
	2. 5 yr, F	2. Oral Pen, 1 wk: asymptomatic
Rehder, 1998, United States[61]	1. 3 yr, M	1. Oral Pen, 2 wk	1. 2 wk later, erythema and GAS positive: erythromycin, for 1 mo; no recurrence (including culture)
	2. 3 yr, M	2. Oral Pen, 2 wk	2. No recurrence (including cultures)
	3. 4 yr, M	3. Oral Pen, 3 wk	3. Perianal cultures positive after 2 and 3 wk: erythromycin, 10 d: negative culture
	4. 1 yr, F	4. Oral Pen, 3 wk: both conditions cleared	4. All negative
Honig, 1988, United States[62]	4; 15 mo, 6, 8 and 12 yr; 3 M	Oral Pen, 10 d; PID cleared in 3 cases within 10-14 d	The 4th case with PID history of 2 Y: 10 d of erythromycin, cleared PID and negative culture; psoriasis cleared 14-35 d after institution of therapy
Marks, 1988, United States[63]	5 yr, M	Oral Pen, 14 d; rash progressively healed (completely in 17 d)
Duhra, 1990, UK[29]	5 yr, M	Oral Pen, 3 wk: clearance of penile lesion (2 wk), but not perianal, also with positive GAS	Other 2 wk of oral Pen cleared PID and GAS
Goodyear, 1991, United Kingdom[30]	4 yr, M	Oral Pen, 10 d; completely resolved in 2 wk	Follow up 2 mo later: clinically well
Medina, 1992, Spain,[31]	4 Y, M	Topical mupirocin, 10 d: Completely resolved	Negative cultures 1 wk and 1 mo later
Montemarano, 1993, United States[32]	3 Y, M	Oral erythromycin, 10 d: Rapid cure
Guppy, 1993, Australia[33]	1. 7 yr, M	1. Oral Pen, 10 d	1. After stopping Pen, rectal bleeding: Cefaclor, 10 d, no recurrence
	2-3. His 2 brothers, 5 and 2.5 yr	2. Oral Pen, 10 d	2. No recurrence
		3. Oral Pen, 10 d, initially improved	3. 3 mo later: Persistent perianal infection: erythromycin
	4. 4 yr, M	4. Oral Pen, 2 wk, incomplete resolution	4. Erythromycin, 4 wk: Complete resolution
Paradisi M, 1993, Italy[34]	3 yr, M	Topical erythromycin, 15 d: Complete clinical and bacteriologic resolution	No recurrence
van Zeijl, 1996, Netherlands[36]	4; 3 M (1, 6 and 8 yr, the last 2 brothers); 1 F (2 yr)	Oral Pen, 10 d ± mupirocin or fucidin Oral amoxicillin + fucidin
Saxen, 1997, Finland[37]	1. 3 yr, M	1. Oral Pen, 10 d: clearance within 2 d	1. 1 wk after stopping Pen: PID recurrence, with GAS positive; oral cephalexin: good results
Berlin, 1997, United States[38]	3 yr, M	IV antibiotics (not mentioned)	Symptoms resolved entirely after 2 wk
Bugatti, 1998, Italy[39]	12 yr, M	Amoxicillin, 10 d: Rapid resolution of symptoms
Adams, 1999, Canada[40]	1 yr, M	Oral Pen and topical mupirocin, 10 d
Roos, 1999, Sweden[41]	5 yr, M	Cefadroxil plus topical fucidin, 10 d	No recurrence
Velez, 1999, Spain[42]	2 yr, M	Cefaclor, 10 ds: complete healing	2 wk after therapy: Acral (hands and feet) scarlatiniform desquamation
Herbst, 2000, Germany[9]	4 yr, M,	Oral Pen and topical fucidin, 2 wk: Complete healing (including culture)
Brilliant, 2000, United States[43]	1. 4 yr, M	1. Oral amoxicillin, dramatic improvement 1 d
	2-3. 2 mo and 30 mo	2-3. Same effective therapy
	4. 4 yr, F	4. Same effective therapy
Balasubramanian, 2000, India[44]	1. 13 mo, M	Oral Pen, 10 d; symptoms clearance in 3 d
	2.11 mo, M
	3. 13 mo, F
Heidelberger, Germany, 2000[45]	1. 6 yr, M	1: Oral Pen, 10 d
	2. 9 yr, M	2. Same plus topical clioquinol; in both cases, all lesions disappeared
Nowicki, 2000, United States[46]	7 yr, M	Oral Pen: Symptoms and signs disappeared	1 wk following Pen, peeling from his fingers tip (toes not involved)
Soulliet, 2000, France[13]	7 yr, F	Amoxicillin, 10 d; perianal lesions cleared by day 2
Lunghi, 2001, Italy[47]	Brother (4 yr) and sister (6 yr)	IM Pen, 4 wk, plus local mupirocin	Complete resolution (with negative culture) within 4 wk; no relapse in 4 mo
Huang, 2003, Taiwan[49]	6 yr, M	Oral Pen and topical mupirocin, 14 d: clinical healing after 4 d	After starting Pen: desquamation of fingers and perioral skin
Reimer, 2004, Sweden[50]	1. 4 yr, M	Oral Pen in all cases: quickly healed
	2. 6 yr, M
	3. 4 yr, F
Takeshita, 2006, Japan[51]	1. 2 yr, F	Oral antibiotics: rapid resolution of the condition
	2. 6 mo, M
Usuki, 2006, Japan[52]	5 yr, F	Oral and topical antibiotics
Ulger, 2007, Turkey[53]	3 yr, M	Oral Pen, 2 wk; topical corticosteroids for GP; all lesions healed	No recurrence
Greisser, 2008, Swiss[54]	7 yr, M	Oral amoxicillin, 6 d: Rapid improvement	No recurrence
Ledoux, 2009, France[55]	4 yr, M	Josamycin 1 mo and desonide for GP: All symptoms subsided	No relapse in 6 mo
Rasi, 2009, Iran[56]	4 yr, M	Oral amoxicillin, 10 d: Clinical response within 3 d, healed in 3 wk; GAS negative after 3 wk	No improvement of psoriatic lesions
Block, 2013, United States[57]	1. 2 mo, F	Amoxicillin, 10 d, in both patients	No recurrence in both cases
	2. 4 mo, F
Theotokatou, 2014, Greece[58]	1. 8 yr, M	Oral cefuroxime and topical mupirocin for both brothers: effective by day 4
	2. 10 yr, M, brother
Zhang 2016, Canada[3]	1. 4 yr, M	1. Oral cefuroxime, 7 d plus topical fucidin	1. 3 mo later: Throat and anus GAS negative; PID cleared
	2. 4 yr, M	2. Oral cefuroxime, 7 d plus betamethasone for GP	2. 2 wk later, perianal GBS positive: topical Fucidin; 3 mo later: GBS negative and cleared GP
	3. 3 yr, F	3. Oral cefuroxime, 7 d plus topical fucidin; persistent erythema and discharge	3. Vulvar culture: GCS and GBS, perianal culture: GCS; culture from vaginal introitus: positive GAS: oral amoxicillin, 10 d
Garritsen, 2017, Netherlands[60]	19 mo, M	Oral Pen plus mometasone for GP; 4 wk: PID and GP significantly improved
Serban, present study, Romania	1. 9 yr 4 mo, M	1. Spiramycin and topical mupirocin, 2 wk: improvement after 2 d; perianal culture negative on day 7; completely healed after 12 d	1. No recurrence after 2 yr
	2. 9 yr 6 mo, M	2. Spiramycin, 2 wk: improvement since day 2; negative perianal culture on day 7; completely healed after 1 wk	2. No recurrence after 7 mo
	3. 11 yr 9 mo, M	3. Spiramycin and topical bacitracin plus neomycin, 3 wk: improvement after 5 d; negative perianal culture on day 7; healed completely after 2 wk	3. No recurrence after 2 mo

F: Female; GAS: Group A beta-hemolytic streptococci; GBS: Group B beta-hemolytic streptococci; GCS: Group C beta-hemolytic streptococci; GP: Guttate psoriasis; IM: Intramuscular; IV: Intravenous; M: Male; Pen: Penicillin; PID: Perianal infectious dermatitis.

Table 5 Previous investigations, diagnoses and therapies in children with perianal infectious dermatitis

Name, yr, country	Population size; age; sex	Previous performed investigations and/or suspected diagnosis	Previous therapy
Spear, 1985, United States[28]	14; mean age 3.9 yr (range: 1-10 yr); M/F: 3.7/1	2 proctoscopies under general anesthesia, upper gastrointestinal x-ray series, barium enema; anal fissure, IBD, behavior disturbance, psychogenic stool holding, psoriasis, candidiasis, ammoniacal diaper dermatitis	Laxatives, suppositories, hydrocortisone, polymyxin, bacitracin and neomycin, povidone-iodine, triamcinolone
Farmer, 1987, United Kingdom[65]	1. 4 yr, M	1. Anal pinworms (negative)	1. Piperazine, miconazole, and hydrocortisone cream
	2. 5 yr, F	2. Anal pinworms (negative)	2. Clotrimazole cream
Kokx, 1987, United States[4]	31; 7 mo to 8 yr, mean 4.25 ± 1.8 yr; M 77%	Hemorrhoids, poor hygiene, perianal allergy to toilet paper perfumes, rectal fissures, and/or constipation
Rehder, 1998, United States[61]	1. 3 yr, M		1. Soaks, topical antifungals and corticosteroids
	2. 3 yr, M		2. Topical hydrocortisone, nystatin, triamcinolone and zinc oxide
	3. 4 yr, M	3. Pinworms	3. Oral cefaclor, with clearing of erythema, but recurrence
Marks, 1988, United States[63]	5 yr, M	Pinworms and stool for ova and parasites: negative	Topical A and D ointment, hydrocortisone, ketoconazole
Duhra, 1990, United Kingdom[29]	5 yr, M	Considered as possible case of sexual abuse; threadworms, candidiasis, psoriasis and eczema	Treatment for threadworms, candidiasis, psoriasis and eczema
Goodyear, 1991, United Kingdom[30]	4 yr, M	Examination under anesthesia and proctoscopy	Stool softeners, stimulant laxatives, topical anesthetics, steroid and antifungal creams
Montemarano, 1993, United States[32]	3 yr, M		Topical and oral nystatin
Grant, 1993, United Kingdom[10]	20; 5 mo to 12 yr; 75% M	2 cases: suspected Crohn’s disease 1 case: suspected sexual abuse	3 patients treated for worms, 7 treated for constipation, 5 topical treatment (steroids, lignocaine, eosin, fucidin)
Guppy, 1993, Australia[33]	1. 7 yr, M		1. Topical antifungal, antibacterial and steroid creams, oral pyrantel embonate and metronidazole
	2-3. 5 and 2.5 yr		2-3. Various antifungal, antibacterial and steroid creams, oral pyrantel embonate
	4. 4 yr, M		4. Local nystatin, hydrocortisone; oral pyrantel embonate
Patrizi, 1994, Italy[22]	5; 4-10 yr; 3 M		Topical agents, including steroid cream
Bugatti, 1998, Italy[39]	12 yr, M		Topical antifungal agents
Adams, 1999, Canada[40]	1 yr, M		Topical corticosteroids and clotrimazole
Roos, 1999, Sweden[41]	5 yr, M		Topical steroids
Herbst, 2000, Germany[9]	4 yr, M		Various ointments for the last several months
Brilliant, 2000, United States[43]	1. 4 yr, M		1. Topical ointment and baby powder, topical antifungal
	4. 4 yr, F		4. Topical antifungal
Heidelberger, 2000, Germany[45]	1. 6 yr, M		1. Tannolact seat baths and topical tetracycline
	2. 9 yr, M		2. Tannolact seat baths and topical clotrimazole
Soulliet, 2000, France[13]	7 yr, F	Candidiasis	Nystatin unsuccessful for suspected candidiasis
Lunghi, 2001, Italy[47]	Brother (4 yr) and sister (6 yr)		Both: Local and oral antifungal drugs for 4 mo
Mateo, 2002, Spain[19]	10; 9 mo to 7 yr; 6 M		4 cases: 2 steroids cream, 1 clotrimazole cream and 1 betamethasone and clotrimazole cream
Reimer,2004, Sweden[50]	1. 4 yr, M	1. Pinworms (negative)
	3. 4 yr, F		3. Local ointment (kenacutan)
Jongen, 2008, Germany[8]	21; < 14 yr (mean age 6.3 yr), 76% M	Anoscopy and rectoscopy: negative	Topical agents (zinc paste, corticosteroids, antimycotic ointments)
Rasi, 2009, Iran[56]	4 yr, M		Topical antibiotics, steroids and antifungal creams, 3 mo
Zhang, 2016, Canada[3]	1: 4 yr, M		1. Topical terbinafine and hydrocortisone acetate
	3: 3 yr, F		3. Gentle skin care, zinc barrier cream, topical antifungals, corticosteroids, and mupirocin
Garritsen, 2017, Netherlands[60]	19 mo, M		Topical corticosteroids and antimycotic agents
Serban, present paper, Romania	1. 9 yr 4 mo, M	1. Psoriasis, pinworms, candidiasis, eczema; Hospitalization in 6 public clinics and 2 private hospitals; upper and lower endoscopy under general anesthesia; magnetic resonance enterography – all negative; considered as Crohn’s disease and sent to our clinic	1. Topical antibiotics, steroids, antifungal and anesthetics creams; oral antiallergics
	2. 9 yr 6 mo, M	2. Pinworms, intestinal dysbiosis	2. Oral probiotics and therapy against worms; topical baneocin and neomycin, cortisone and anti-hemorrhoids
	3. 11 yr 9 mo, M	3. Eczema, anal fissure, constipation	3. Oral probiotics, osmotic laxatives and stool softeners; topical hydrocortisone, cicatrizants

F: Female; IBD: Inflammatory bowel disease; M: Male.