Original article A new proposal for a clinical-oriented subclassifi- cation of baboon syndrome and a review of baboon syndrome Atsushi Miyahara1, 2, Hisashi Kawashima2, Yukari Okubo3 and Akinori Hoshika2 drug-related intertriginous and flexural exanthema Summary (SDRIFE), classical baboon syndrome, topical Objective: To review baboon syndrome (BS). drug-induced baboon syndrome, systemic drug- Data Sources: Date sources were obtained from induced baboon syndrome, recall phenomenon, p-i PubMed and Google Scholar: Photographs of (pharmacologic interaction with immuno-receptors) baboon syndrome were obtained from our concept. patient. Study Selections: PubMed and Google Scholar Introduction were searched up to June 30, 2010. The search The term “baboon syndrome”(BS) was terms were “baboon syndrome”, “SDRIFE” and introduced in 1984 to describe a mercury-induced “thimerosal allergy”. Reverse references from characteristic eruption with previous sensitization to relevant articles and Google Scholar were also mercury1. It presents with a diffuse symmetrical used. As BS is a classical disease and cases of erythema, predominantly on major flexural areas, offending agents were relatively old, some and an inverted triangular or V-shaped erythema on references were more than five years old. In both upper antero-medial thighs1. BS was named order to gather as many cases of offending agents after the red bottomed baboon1. as possible, more than 50 references were Recently it has been revealed that an eruption collected. which resembles mercury-induced BS was due not Results and Conclusion: We divided BS into as 4 only to mercury but also other metals, drugs and groups; classical baboon syndrome, topical drug- natural products, with or without previous induced baboon syndrome, systemic drug- sensitization to offending or related drug(s). Despite induced baboon syndrome and symmetrical its characteristic eruptions, the name “baboon drug-related intertriginous and flexural syndrome” is not well understood among doctors exanthema (SDRIFE). The pathomechanism of except for dermatologists. Therefore BS may be BS is still unknown. A delayed type of wrongly diagnosed as candida intertrigo or diaper hypersensitivity reaction, a recall phenomenon, dermatitis, which can lead to the wrong treatment. pharmacologic interaction with immune- There is also the possibility that doctors, parents or receptors and anatomical factors may be even patients may overlook the symptoms. involved in the causation of BS. (Asian Pac J Moreover, the definition of BS is not clear. In the Allergy Immunol 2011;29:150-60) present paper we try to establish the definition of BS and to review this syndrome. Key words: baboon syndrome, allergic contact dermatitis syndrome (ACDS), systemic reactivation History and classification of allergic contact dermatitis (SRCD), symmetrical In 1983, Nakayama et al. reported characteristic eruptions induced by mercury2. A generalized rash appearing after inhalation of mercury vapor has also 3 From the 1Department of Pediatrics, Tokyo Medical been reported . It presented as a diffuse University. symmetrical erythema predominantly on major 2Department of Dermatology, Tokyo Medical University. flexural areas and an inverted triangular or V-shaped Corresponding author: Atsushi MIYAHARA erythema on both upper antero-medial thighs. It E-mail: [email protected] mostly appeared after breaking a clinical Submitted date: 5/11/2010 thermometer or during dental treatment by persons Accepted date: 18/3/2011 with a history of contact dermatitis to Mercurochrome. 150 Review of baboon syndrome Table 1. Definition of SDRIFE6 However, cases of drug-related BS without a previous cutaneous sensitization cannot be 1. Exposure to a systemically administered drug either following the first or subsequent dose (excluding contact allergens) categorized as stage 3A or 3B of ACDS. In 2004, 2. Sharply demarcated erythema of the gluteal/perianal area Häusermann et al. proposed that systemically and/or V-shaped erythema of the inguinal/perigenital area 3. Involvement of at least one other intertriginous/flexural induced drug-related BS could occur without localization previous cutaneous sensitization(symmetrical drug- 4. Symmetry of affected areas related intertriginous and flexural exanthema, 6 5. Absence of systemic symptoms and signs. SDRIFE) . SDRIFE specifically refers to the Abbreviations: SDRIFE, systemic reactivation of allergic contact distinctive clinical pattern of these drug eruptions dermatitis. and the following diagnostic criteria are proposed: 1) exposure to a systemically administrated drug either at the first or repeated dose (excluding contact In 1984, the term baboon syndrome(BS) was allergens; 2) sharply demarcated erythema of the introduced to describe the characteristic gluteal area and/or V-shaped erythema of the development of diffuse bright red erythema 1 inguinal/perigenital area; 3) involvement of at least resembling the red bottom of baboons . In this one other intertriginous/flexural localization; 4) paper, this reaction was noted in 3 patients, symmetry of affected areas; and 5) absence of previously sensitized by topical contact, upon systemic symptoms and signs, as listed in Table 16. subsequent systemic exposure to the same substance 1 SDRIFE differs from stage 3A and 3B of ACDS (mercury, nickel and ampicillin) . which are associated with previous sensitization. The name of BS is very catchy and easy to use. There are several reasons of why Häusermann et However, the term „BS‟ is so widely used that it is al. proposed SDRIFE6: first, BS is historically difficult to define the real essence of this syndrome. equated with the gluteal erythema induced by There was confusion over whether other gluteal systemic absorption of mercury and other agents, erythema such as candida intertrigo or diaper 4 often after a previous cutaneous sensitization with dermatitis should be called BS or a BS-like pattern . the same substance. Second, based on recent results, Therefore, a specific definition of BS was made. the previous classification does not reflect the entire The concept of allergic contact dermatitis 5 range of clinical symptoms and signs of BS. Third, syndrome (ACDS) was developed by Lachapello according to various investigators, BS incorporates a recently. There are four clinical stages of ACDS spectrum of diseases. with a previous cutaneous sensitization comprising: In 2009, Özkaya suggested a subclassification of localized ACDS(stage1), regional dissemination of BS, based on the causative agent and previous ACDS via lymphatic vessels(stage2), and sensitization: contact allergen-induced BS(excluding hematogenous dissemination of ACDS to distance drugs), contact allergenic drug-induced BS and non- sites (stage 3A) or systemic reactivation of ACDS contact allergenic drug-induced BS4. Non-contact (stage 3B). Stage 3A of ACDS can be defined as a allergenic drug-induced BS is the same as SDRIFE. generalized dissemination of skin lesions from the This classification has merit, but there is still primary site of application of the allergen via blood disagreement about how to classify cases of vessels; whereas in stage 3B, allergen(s) are infections or other dermatoses affecting the gluteal introduced by systemic administration (ingestion, region. inhalation or injection). Patients with stage 3B of In this article, we paraphrased contact allergen- ACDS were previously sensitized to the same induced BS (excluding drugs) as classical BS, BS of contact allergen or chemically closely related ACDS stage 3A as topical drug-induced BS, BS of substance(s) to the contact allergen. Lachapello ACDS stage 3B (or SRCD) as systemic drug- called stage 3B of ACDS as systemic reactivation of 5 induced BS and non-contact allergenic drug-induced allergic contact dermatitis (SRCD) . The clinical BS as SDRIFE. We also propose that eruptions signs observed in stage 3B of ACDS share a similar resembling BS induced by generalized infections be pattern with skin lesions observed in stage 3A of describes as infection-induced BS-like pattern and ACDS. The only difference is that in stage 3B, no that other dermatoses affecting the gluteal region current skin contact occurs. Drug-related BS with a without generalized infections(candida intertrigo previous cutaneous sensitization is a special case of and diaper dermatitis) be described as BS-like stage 3A or 3B of ACDS. pattern. This subclassification is shown in Table 2. 151 Asian Pac J Allergy Immunol 2011;29:150-60 Table 2. Classification of baboon syndrome infection- topical drug- systemic drug - BS-like Our proposal classical BS SDRIFE induced BS-like induced BS induced BS pattern pattern Häusermann P et al.6 stage 3A of stage 3B of SDRIFE ACDS ACDS/ SRCD 4 Özkaya E BS BS type 2:contact allergenic drug- BS type type1:contact induced BS 3:non-contact allergen- allergenic induced BS drug-induced (excluding BS drugs) previous sensitization + + + - - - drug induced - + + + - - generalized infection - - - - + - other dermatoses affecting the gluteal - - - - + + region patch tests +- + + +- - - current skin contact +- + - - - - Abbreviations: BS, baboon syndrome; ACDS, allergic contact dermatitis syndrome; SRCD, systemic reactivation of allergic contact dermatitis; SDRIFE, symmetrical drug-related intertriginous and flexural exanthema. Etiologies ingestion of mercury-containing homeopathic Causative agents of BS have been reported by medicine 10 and walking around cinnabar (mercuric various investigators (Table 3).