- Email: [email protected]
Baboon syndrome and toxic erythema of chemotherapy: Fold (intertriginous) dermatoses
Clinics in Dermatology (2015) 33, 462–465
Baboon syndrome and toxic erythema of chemotherapy: Fold (intertriginous) dermatoses Ronni Wolf, MD a,⁎, Yalçın Tüzün, MD b a
The Dermatology Unit, Kaplan Medical Center, Rechovot, Israel, affiliated with the School of Medicine, Hebrew University and Hadassah Medical Center, Jerusalem b Department of Dermatology, Istanbul University Cerrahpaşa Medical Faculty, Istanbul, Turkey
Abstract Three decades ago, researchers described an eruption with a very characteristic distribution pattern that was confined to the buttocks and the intertriginous and flexor areas. They gave this reaction pattern one of the most unforgettable names in dermatology, baboon syndrome (BS), due to the characteristic, bright-red, well-demarcated eruption predominantly on the buttocks and genital area, reminiscent of the red bottom of a baboon. The authors described three cases provoked by ampicillin, nickel, and mercury. They were convinced that BS represented a special form of hematogenous or systemic contact-type dermatitis, but several important papers that appeared during the past decade disagreed and suggested that BS should be distinguished from hematogenous or systemic contact-type dermatitis. A new acronym, SDRIFE (symmetrical drug-related intertriginous and flexoral exanthema), was proposed along with five diagnostic criteria: (1) exposure to a systemically administered drug at the time of first or repeated doses (contact allergens excluded), (2) sharply demarcated erythema of the gluteal/perianal area and/or V-shaped erythema of the inguinal/perigenital area, (3) involvement of at least one other intertriginous/flexural fold, (4) symmetry of affected areas, and (5) absence of systemic symptoms and signs. Although there are merits to the arguments in favor of SDRIFE, many of us still prefer to use the wittier name baboon syndrome, and even more authors use both terms. We confess that we find it difficult to relinquish the term BS, which has served us so well for years; however, recognition, familiarity, and knowledge of the characteristics of this form of drug eruption must supersede sentimental attachment to a certain nomenclature and so, however reluctantly, we must embrace change. Another intertriginous drug eruption is the one induced by chemotherapy. Toxic erythema of chemotherapy (TEC) is a useful clinical term that recently has been introduced to describe this group of chemotherapy-induced eruptions. This group of overlapping toxic reactions is characterized by areas of painful erythema often accompanied by edema usually involving the hands and feet, intertriginous zones (eg, axilla, groin), and, less often, the elbows, knees, and ears. Toxic erythema of chemotherapy is briefly discussed. © 2015 Elsevier Inc. All rights reserved.
⁎ Corresponding author. Fax: + 972-9-9560978. E-mail address: [email protected] (R. Wolf). http://dx.doi.org/10.1016/j.clindermatol.2015.04.008 0738-081X/© 2015 Elsevier Inc. All rights reserved.
Baboon syndrome and toxic erythema of chemotherapy
Introduction of the term baboon syndrome Drug-associated eruptions can mimic a variety of skin diseases, but intertrigo is generally easily distinguishable and is, therefore, not listed in the differential diagnosis of these kinds of reactions. We will concentrate on this type of drug eruption and present the main characteristics of intertriginous drug reactions. In 1984, researchers described an eruption with a very characteristic distribution pattern that was confined to the buttocks and the intertriginous and flexor areas.1 They gave this reaction pattern one of the most memorable names in dermatology, baboon syndrome (BS), due to the characteristic bright-red, well-demarcated eruption, predominantly located on the buttocks and genital area, reminiscent of the red bottom of the baboon. The authors described three cases provoked by ampicillin, nickel, and mercury. They were convinced that BS represented a special form of hematogenous or systehoimic contact-type dermatitis (title: “The BS: Systemically-induced allergic contact dermatitis”), because all of their patients had been previously sensitized by topical exposure to the allergen. Interestingly, the patient with an ampicillin allergy had been sensitized by a gelatin foam moistened with an ampicillin solution applied in the middle ear during a stapedectomy. The authors admitted that “a rationale for the distribution pattern is difficult to offer.” Other authors who later described the syndrome accepted the hypothesis.2 In a textbook on contact dermatitis,3 systemic contact dermatitis is divided into (1) “Dermatitis in areas of previous exposure” (flare-up of dermatitis at positive patch test sites), and (2) “Dermatitis on previously unaffected skin.” BS is mentioned in this group together with vesicular hand eczema, flexural dermatitis, maculopapular rash (toxicoderma), and vasculitis-like lesions.
Is BS a type of systemic contact dermatitis? Several important papers that appeared during the last decade4–6 suggested that BS should be distinguished from hematogenous or systemic contact-type dermatitis (SCD). In two papers that proposed criteria for diagnosing this syndrome, the first criterion was “Exposure to a systemically administered drug, first or repeated doses (contact allergen excluded).”4,5 In a review of 100 published cases of BS, 50 were found to be drug induced. Of these, only eight were considered representatives of systemically induced allergic contact dermatitis, and the remaining 42 reported cases were considered examples of drug eruptions of oral or intravenous drugs with no history of previous cutaneous sensitization.5
Reported cases In that excellent 2004 review of 50 cases of BS,5 the main clinical findings included sharp demarcation of a V-shaped erythema in inguinal/genital and gluteal/perianal areas and,
463 in most cases, additional involvement of at least one other flexural or intertriginous fold. In 14 of 42 cases of drug eruptions (excluding the eight cases of SCD), amoxicillin was the culpable drug. Thirty of the 42 patients were men, and the latency periods were between hours and few days. Other cases have been reported since then, some of them using the proposed name symmetric drug-related intertriginous and flexural exanthema (SDRIFE) and others using the terms SCD or BS.7,8 In contrast to the homogeneity of BS cases in terms of clinical distribution, range of primary cutaneous lesions, latency period after drug intake, and courses, the syndrome’s histologic picture is quite variable. The main finding in drug-induced BS is the superficial perivascular infiltrate composed of mononuclear cells, sometimes including neutrophils and eosinophils. Other less common findings are vacuolar and hydropic alterations of the basal cell layer with necrotic keratinocytes, and histologic pictures seen in bullous drug eruption, fixed drug eruption, and others.5
Terminology, classification, and criteria proposed for BS The new acronym for this syndrome, SDRIFE, was proposed in a review5 and five diagnostic criteria were suggested for it: (1) exposure to a systemically administered drug at the time of first or repeated doses (contact allergens excluded); (2) sharply demarcated erythema of the gluteal/ perianal area and/or V-shaped erythema of the inguinal/ perigenital area; (3) involvement of at least one other intertriginous/flexural fold; (4) symmetry of affected areas; and (5) absence of systemic symptoms and signs. After its introduction, the term BS was widely used for many conditions other than SDRIFE—for example, the historical definition of characteristic mercury-induced eruptions with previous sensitization to mercury, topical drug-induced syndrome, SCD-induced BS, and other gluteal erythemas, such as candida intertrigo, or diaper dermatitis, etc. A new proposal for a clinically oriented subclassification of BS was recently suggested by a Japanese group of dermatologists.8 They divided BS into four groups. The first was classical BS, which is often historically equated with a mercury-induced exanthema resulting from SCD in patients with previous contact sensitization. Although there are many case reports on this type of BS, the number of causative agents are few and include mercury, nickel, balsam of Peru, and poison ivy. The second type was topical drug-induced BS and the third was systemic drug-induced BS, both types representing an SCD, meaning that the patients had been sensitized to the offending drug via skin contact. The formal difference between the two types is the method of exposure to the challenge dose—that is, topical (via absorption of the drug from the skin or mucosal surfaces) or systemic. The fourth type was non-contact allergenic drug-induced BS,
464 which is equivalent to SDRIFE. There is a further small group that they termed infection-induced BS-like pattern.8 The question arises as to whether we should adopt this latter classification and, indeed, whether we really need it. Should we prefer SDRIFE over the old and familiar, catchy and simple term, BS? As very often occurs in medicine, there are conflicts and disagreements over issues dealing with names, terminology, and classifications. The arguments in favor of the acronym SDRIFE as presented by its introducers9 are reasonable and even convincing, but many still prefer to use the wittier name baboon syndrome,10,11 and even more authors use both terms.12–17 We confess that we find it difficult to relinquish the term baboon syndrome, which has served us so well for years.
Pathogenesis The precise mechanism of BS pathogenesis is still unknown. As many as three decades ago it was noted that “a rationale for the distribution pattern is difficult to offer,”1 and the dilemma has persisted to this day. There is evidence for the role of a T-cell–mediated delayed type of hypersensitivity reaction. Immunohistologic findings on skin biopsies have indicated an infiltration with predominantly CD4+-positive T cells in the dermis.18,19 Positive patch tests, delayed skin tests,20 and lymphocyte transformation tests7,21further support a T-cell–mediated delayed-type hypersensitivity pathomechanism. The main enigma continues to be the reason for the localization of this bizarre eruption. Several hypothetical explanations have been offered for its peculiar clinical manifestation.22 One hypothesis is that BS may represent a form of recall phenomenon from previous mechanical stimulation or a form of intertrigo that had occurred in the past in the same areas as those of the new drug eruption. The previous dermatitis may have been severe diaper dermatitis in infancy, contact dermatitis to any allergen or irritant, or other forms of typical intertrigo. Another relevant and equally plausible explanation for the predilection of this localization is the high density of eccrine glands together with the higher concentrations of the drugs in the eccrine ducts where they are excreted. The occlusive phenomenon in intertriginous zones might also contribute to the localization. Further supporting this theory is the development of localized areas of eccrine squamous syringometaplasia, a feature particularly applicable to chemotherapeutic drugs.23
Chemotherapy-induced intertrigo-like eruption: Toxic erythema of chemotherapy Diagnosis and recognition of chemotherapy-induced eruptions is especially important and challenging. The clinical situation in oncologic patients receiving chemotherapy often
R. Wolf, Y. Tüzün demands immediate recognition and action because these patients are prone to life-threatening conditions, such as infections, drug reactions from the multiple drugs they usually receive (especially antibiotics), and graft-versus-host disease. These and others should be promptly diagnosed and differentiated from chemotherapy-induced eruptions; furthermore, it must be borne in mind that many of the classic clinical features that aid in diagnosis may look different in immunocompromised patients. Toxic erythema of chemotherapy (TEC) is a useful clinical term that has recently been introduced to describe a group of chemotherapy-induced eruptions.23 This group of overlapping toxic reactions is characterized by areas of painful erythema (and oftentimes edema) that usually involve the hands and feet, intertriginous zones (eg, axilla, groin) and, less often, the elbows, knees, and ears. The eruptions may have a bullous component, they are selflimited, and they often resolve with desquamation and postinflammatory hyperpigmentation. Over the past decades, these reactions have unfortunately been collected under multiple names, some of them emphasizing the location (eg, intertriginous eruption associated with chemotherapy, intertrigo-like eruption, hand and foot syndrome, toxic acral erythema, and others), and, even worse, by the histologic pattern (eg, eccrine squamous syringometaplasia, chemotherapyinduced epidermal dysmaturation, chemotherapy-induced neutrophilic eccrine hidradenitis, and others). Although most of the authors find the term TEC to be sufficiently appropriate and to allow for ease in communication with nondermatologists as well as reflecting the nonallergic and noninfectious nature of the eruption, other authors 24 do not. The chemotherapeutic agents most often associated with TEC are polyethelene glycol-coated liposomal doxorubicin, cytarabine, 5-fluorouracil, capecitabine, and docetaxel. The eruption usually appears 2 days to 3 weeks after the administration of chemotherapeutic agents. It might recur when the same or higher doses of chemotherapy is administrated. A delayed onset of up to several months can be seen in patients who are receiving lower doses of chemotherapeutic drugs. The main histologic feature of TEC—particularly the form that involves the intertriginous areas24—is eccrine squamous syringometaplasia, which is characterized by the transformation of the eccrine cuboidal epithelium into two or more layers of squamous cells with intercellular bridges. Other histologic findings25 are atypia (characterized by enlarged cell and nuclear size and nuclear pleomorphism) and apoptosis of keratinocytes, loss of polarity of epidermal cells and crowding of keratinocytes, vacuolar degeneration of the basal layer, and dermal edema. The exact pathogenesis of TEC remains unclear. One plausible explanation is that the chemotherapeutic agents that are excreted via eccrine sweat exert a toxic insult to the cells of the straight portion of the eccrine duct, the acrosyringium and the epidermis. The localization of the reaction could thus
Baboon syndrome and toxic erythema of chemotherapy be explained by the high density of eccrine glands on the palms and soles plus some occlusive phenomenon in intertriginous areas.26 Treatments of TEC remain nonspecific and primarily palliative. They include cool compresses, analgesics, bland emollients, topical corticosteroids, and topical antibiotics. Prevention of recurrence involves dose reduction, lengthening the interval between cycles, or discontinuation of the offending agents when possible. What is most essential, however, is early recognition of TEC, which may prevent the inappropriate use of systemic immunosuppressives for presumed hypersensitivity reaction or graft-versus-host disease or systemic antimicrobials for assumed infections.
References 1. Andersen KE, Hjorth N, Menne T. The baboon syndrome: Systemically-induced allergic contact dermatitis. Contact Dermatitis. 1984;10: 97-100. 2. Wolf R, Orion E, Matz H. The baboon syndrome or intertriginous drug eruption: A report of eleven cases and a second look at its pathomechanism. Dermatol Online J. 2003;9:2. 3. Veien N, Menne T. Systemic contact dermatitis. In: Frosch P, Menne T, Lepoittevin JP, eds. Contact Dermatitis. 3rd ed. Berlin: Springer; 2006. p. 295-308. 4. Arnold AW, Hausermann P, Bach S, Bircher AJ. Recurrent flexural exanthema (SDRIFE or baboon syndrome) after administration of two different iodinated radio contrast media. Dermatology. 2007;214:89-93. 5. Hausermann P, Harr T, Bircher AJ. Baboon syndrome resulting from systemic drugs: Is there strife between SDRIFE and allergic contact dermatitis syndrome? Contact Dermatitis. 2004;51:297-310. 6. Wolf R, Elman M, Brenner S. Drug-induced “intertrigo." Int J Dermatol. 1993;32:515-516. 7. Winnicki M, Shear NH. A systematic approach to systemic contact dermatitis and symmetric drug-related intertriginous and flexural exanthema (SDRIFE): A closer look at these conditions and an approach to intertriginous eruptions. Am J Clin Dermatol. 2011;12:171-180. 8. Miyahara A, Kawashima H, Okubo Y, Hoshika A. A new proposal for a clinical-oriented subclassification of baboon syndrome and a review of baboon syndrome. Asian Pac J Allergy Immunol. 2011;29:150-160. 9. Hausermann P, Bircher AJ. SDRIFE—another acronym for a distinct cutaneous drug exanthema: Do we really need it? Dermatology. 2007;214:1-2.
465 10. Akkari H, Belhadjali H, Youssef M, Mokni S, Zili J. Baboon syndrome induced by hydroxyzine. Indian J Dermatol. 2013;58:244. 11. Ozdemir H, Celik NG, Tapisiz A, et al. Baboon syndrome induced by oral antitussive-decongestant agent in a child. Turk J Pediatr. 2010;52: 659-661. 12. Handisurya A, Stingl G, Wohrl S. SDRIFE (baboon syndrome) induced by penicillin. Clin Exp Dermatol. 2009;34:355-357. 13. Chong WS, Lim HL. Symmetrical drug-related intertriginous and flexural exanthema (baboon syndrome) with fever induced by oral cloxacillin: Does fever confound the diagnosis? J Dermatol. 2010;37: 830-832. 14. Kardaun SH, Tupker RA. Symmetrical drug-related intertriginous and flexural exanthema (Baboon syndrome) induced by omeprazole. Int J Dermatol. 2012;51:1134-1137. 15. Dogru M, Ozmen S, Ginis T, Duman H, Bostanci I. Symmetrical drug-related intertriginous and flexural exanthema (baboon syndrome) induced by amoxicillin-clavulanate. Pediatr Dermatol. 2012;29: 770-771. 16. Culav I, Ljubojevic S, Buzina DS. Baboon syndrome/SDRIFE due to sulfamethoxazole-trimethoprim. Int J Dermatol. 2013;52:1159-1160. 17. Lugovic-Mihic L, Duvancic T, Vucic M, Situm M, Kolic M, Mihic J. SDRIFE (baboon syndrome) due to paracetamol: Case report. Acta Dermatovenerol Croat. 2013;21:113-117. 18. Helmbold P, Hegemann B, Dickert C, Marsch WC. Symmetric prychotropic and nonpigmenting fixed drug eruption due to cimetidine (so-called baboon syndrome). Dermatology. 1998;197:402-403. 19. Barbaud A, Trechot P, Granel F, et al. A baboon syndrome induced by intravenous human immunoglobulins: Report of a case and immunological analysis. Dermatology. 1999;199:258-260. 20. Kick G, Przybilla B. Delayed prick test reaction identifies amoxicillin as elicitor of baboon syndrome. Contact Dermatitis. 2000;43:366-367. 21. Tan SC, Tan JW. Symmetrical drug-related intertriginous and flexural exanthema. Curr Opin Allergy Clin Immunol. 2011;11:313-318. 22. Wolf R, Oumeish OY, Parish LC. Intertriginous eruption. Clin Dermatol. 2011;29:173-179. 23. Bolognia JL, Cooper DL, Glusac EJ. Toxic erythema of chemotherapy: A useful clinical term. J Am Acad Dermatol. 2008;59:524-529. 24. Martorell-Calatayud A, Sanmartin O, Botella-Estrada R, et al. Chemotherapy-related bilateral dermatitis associated with eccrine squamous syringometaplasia: Reappraisal of epidemiological, clinical, and pathological features. J Am Acad Dermatol. 2011;64: 1092-1103. 25. Parker TL, Cooper DL, Seropian SE, Bolognia JL. Toxic erythema of chemotherapy following i.v. BU plus fludarabine for allogeneic PBSC transplant. Bone Marrow Transplant. 2013;48:646-650. 26. Jacobi U, Waibler E, Schulze P, et al. Release of doxorubicin in sweat: First step to induce the palmar-plantar erythrodysesthesia syndrome? Ann Oncol. 2005;16:1210-1211.
Baboon syndrome and toxic erythema of chemotherapy: Fold (intertriginous) dermatoses Ronni Wolf, MD a,⁎, Yalçın Tüzün, MD b a
The Dermatology Unit, Kaplan Medical Center, Rechovot, Israel, affiliated with the School of Medicine, Hebrew University and Hadassah Medical Center, Jerusalem b Department of Dermatology, Istanbul University Cerrahpaşa Medical Faculty, Istanbul, Turkey
Abstract Three decades ago, researchers described an eruption with a very characteristic distribution pattern that was confined to the buttocks and the intertriginous and flexor areas. They gave this reaction pattern one of the most unforgettable names in dermatology, baboon syndrome (BS), due to the characteristic, bright-red, well-demarcated eruption predominantly on the buttocks and genital area, reminiscent of the red bottom of a baboon. The authors described three cases provoked by ampicillin, nickel, and mercury. They were convinced that BS represented a special form of hematogenous or systemic contact-type dermatitis, but several important papers that appeared during the past decade disagreed and suggested that BS should be distinguished from hematogenous or systemic contact-type dermatitis. A new acronym, SDRIFE (symmetrical drug-related intertriginous and flexoral exanthema), was proposed along with five diagnostic criteria: (1) exposure to a systemically administered drug at the time of first or repeated doses (contact allergens excluded), (2) sharply demarcated erythema of the gluteal/perianal area and/or V-shaped erythema of the inguinal/perigenital area, (3) involvement of at least one other intertriginous/flexural fold, (4) symmetry of affected areas, and (5) absence of systemic symptoms and signs. Although there are merits to the arguments in favor of SDRIFE, many of us still prefer to use the wittier name baboon syndrome, and even more authors use both terms. We confess that we find it difficult to relinquish the term BS, which has served us so well for years; however, recognition, familiarity, and knowledge of the characteristics of this form of drug eruption must supersede sentimental attachment to a certain nomenclature and so, however reluctantly, we must embrace change. Another intertriginous drug eruption is the one induced by chemotherapy. Toxic erythema of chemotherapy (TEC) is a useful clinical term that recently has been introduced to describe this group of chemotherapy-induced eruptions. This group of overlapping toxic reactions is characterized by areas of painful erythema often accompanied by edema usually involving the hands and feet, intertriginous zones (eg, axilla, groin), and, less often, the elbows, knees, and ears. Toxic erythema of chemotherapy is briefly discussed. © 2015 Elsevier Inc. All rights reserved.
⁎ Corresponding author. Fax: + 972-9-9560978. E-mail address: [email protected] (R. Wolf). http://dx.doi.org/10.1016/j.clindermatol.2015.04.008 0738-081X/© 2015 Elsevier Inc. All rights reserved.
Baboon syndrome and toxic erythema of chemotherapy
Introduction of the term baboon syndrome Drug-associated eruptions can mimic a variety of skin diseases, but intertrigo is generally easily distinguishable and is, therefore, not listed in the differential diagnosis of these kinds of reactions. We will concentrate on this type of drug eruption and present the main characteristics of intertriginous drug reactions. In 1984, researchers described an eruption with a very characteristic distribution pattern that was confined to the buttocks and the intertriginous and flexor areas.1 They gave this reaction pattern one of the most memorable names in dermatology, baboon syndrome (BS), due to the characteristic bright-red, well-demarcated eruption, predominantly located on the buttocks and genital area, reminiscent of the red bottom of the baboon. The authors described three cases provoked by ampicillin, nickel, and mercury. They were convinced that BS represented a special form of hematogenous or systehoimic contact-type dermatitis (title: “The BS: Systemically-induced allergic contact dermatitis”), because all of their patients had been previously sensitized by topical exposure to the allergen. Interestingly, the patient with an ampicillin allergy had been sensitized by a gelatin foam moistened with an ampicillin solution applied in the middle ear during a stapedectomy. The authors admitted that “a rationale for the distribution pattern is difficult to offer.” Other authors who later described the syndrome accepted the hypothesis.2 In a textbook on contact dermatitis,3 systemic contact dermatitis is divided into (1) “Dermatitis in areas of previous exposure” (flare-up of dermatitis at positive patch test sites), and (2) “Dermatitis on previously unaffected skin.” BS is mentioned in this group together with vesicular hand eczema, flexural dermatitis, maculopapular rash (toxicoderma), and vasculitis-like lesions.
Is BS a type of systemic contact dermatitis? Several important papers that appeared during the last decade4–6 suggested that BS should be distinguished from hematogenous or systemic contact-type dermatitis (SCD). In two papers that proposed criteria for diagnosing this syndrome, the first criterion was “Exposure to a systemically administered drug, first or repeated doses (contact allergen excluded).”4,5 In a review of 100 published cases of BS, 50 were found to be drug induced. Of these, only eight were considered representatives of systemically induced allergic contact dermatitis, and the remaining 42 reported cases were considered examples of drug eruptions of oral or intravenous drugs with no history of previous cutaneous sensitization.5
Reported cases In that excellent 2004 review of 50 cases of BS,5 the main clinical findings included sharp demarcation of a V-shaped erythema in inguinal/genital and gluteal/perianal areas and,
463 in most cases, additional involvement of at least one other flexural or intertriginous fold. In 14 of 42 cases of drug eruptions (excluding the eight cases of SCD), amoxicillin was the culpable drug. Thirty of the 42 patients were men, and the latency periods were between hours and few days. Other cases have been reported since then, some of them using the proposed name symmetric drug-related intertriginous and flexural exanthema (SDRIFE) and others using the terms SCD or BS.7,8 In contrast to the homogeneity of BS cases in terms of clinical distribution, range of primary cutaneous lesions, latency period after drug intake, and courses, the syndrome’s histologic picture is quite variable. The main finding in drug-induced BS is the superficial perivascular infiltrate composed of mononuclear cells, sometimes including neutrophils and eosinophils. Other less common findings are vacuolar and hydropic alterations of the basal cell layer with necrotic keratinocytes, and histologic pictures seen in bullous drug eruption, fixed drug eruption, and others.5
Terminology, classification, and criteria proposed for BS The new acronym for this syndrome, SDRIFE, was proposed in a review5 and five diagnostic criteria were suggested for it: (1) exposure to a systemically administered drug at the time of first or repeated doses (contact allergens excluded); (2) sharply demarcated erythema of the gluteal/ perianal area and/or V-shaped erythema of the inguinal/ perigenital area; (3) involvement of at least one other intertriginous/flexural fold; (4) symmetry of affected areas; and (5) absence of systemic symptoms and signs. After its introduction, the term BS was widely used for many conditions other than SDRIFE—for example, the historical definition of characteristic mercury-induced eruptions with previous sensitization to mercury, topical drug-induced syndrome, SCD-induced BS, and other gluteal erythemas, such as candida intertrigo, or diaper dermatitis, etc. A new proposal for a clinically oriented subclassification of BS was recently suggested by a Japanese group of dermatologists.8 They divided BS into four groups. The first was classical BS, which is often historically equated with a mercury-induced exanthema resulting from SCD in patients with previous contact sensitization. Although there are many case reports on this type of BS, the number of causative agents are few and include mercury, nickel, balsam of Peru, and poison ivy. The second type was topical drug-induced BS and the third was systemic drug-induced BS, both types representing an SCD, meaning that the patients had been sensitized to the offending drug via skin contact. The formal difference between the two types is the method of exposure to the challenge dose—that is, topical (via absorption of the drug from the skin or mucosal surfaces) or systemic. The fourth type was non-contact allergenic drug-induced BS,
464 which is equivalent to SDRIFE. There is a further small group that they termed infection-induced BS-like pattern.8 The question arises as to whether we should adopt this latter classification and, indeed, whether we really need it. Should we prefer SDRIFE over the old and familiar, catchy and simple term, BS? As very often occurs in medicine, there are conflicts and disagreements over issues dealing with names, terminology, and classifications. The arguments in favor of the acronym SDRIFE as presented by its introducers9 are reasonable and even convincing, but many still prefer to use the wittier name baboon syndrome,10,11 and even more authors use both terms.12–17 We confess that we find it difficult to relinquish the term baboon syndrome, which has served us so well for years.
Pathogenesis The precise mechanism of BS pathogenesis is still unknown. As many as three decades ago it was noted that “a rationale for the distribution pattern is difficult to offer,”1 and the dilemma has persisted to this day. There is evidence for the role of a T-cell–mediated delayed type of hypersensitivity reaction. Immunohistologic findings on skin biopsies have indicated an infiltration with predominantly CD4+-positive T cells in the dermis.18,19 Positive patch tests, delayed skin tests,20 and lymphocyte transformation tests7,21further support a T-cell–mediated delayed-type hypersensitivity pathomechanism. The main enigma continues to be the reason for the localization of this bizarre eruption. Several hypothetical explanations have been offered for its peculiar clinical manifestation.22 One hypothesis is that BS may represent a form of recall phenomenon from previous mechanical stimulation or a form of intertrigo that had occurred in the past in the same areas as those of the new drug eruption. The previous dermatitis may have been severe diaper dermatitis in infancy, contact dermatitis to any allergen or irritant, or other forms of typical intertrigo. Another relevant and equally plausible explanation for the predilection of this localization is the high density of eccrine glands together with the higher concentrations of the drugs in the eccrine ducts where they are excreted. The occlusive phenomenon in intertriginous zones might also contribute to the localization. Further supporting this theory is the development of localized areas of eccrine squamous syringometaplasia, a feature particularly applicable to chemotherapeutic drugs.23
Chemotherapy-induced intertrigo-like eruption: Toxic erythema of chemotherapy Diagnosis and recognition of chemotherapy-induced eruptions is especially important and challenging. The clinical situation in oncologic patients receiving chemotherapy often
R. Wolf, Y. Tüzün demands immediate recognition and action because these patients are prone to life-threatening conditions, such as infections, drug reactions from the multiple drugs they usually receive (especially antibiotics), and graft-versus-host disease. These and others should be promptly diagnosed and differentiated from chemotherapy-induced eruptions; furthermore, it must be borne in mind that many of the classic clinical features that aid in diagnosis may look different in immunocompromised patients. Toxic erythema of chemotherapy (TEC) is a useful clinical term that has recently been introduced to describe a group of chemotherapy-induced eruptions.23 This group of overlapping toxic reactions is characterized by areas of painful erythema (and oftentimes edema) that usually involve the hands and feet, intertriginous zones (eg, axilla, groin) and, less often, the elbows, knees, and ears. The eruptions may have a bullous component, they are selflimited, and they often resolve with desquamation and postinflammatory hyperpigmentation. Over the past decades, these reactions have unfortunately been collected under multiple names, some of them emphasizing the location (eg, intertriginous eruption associated with chemotherapy, intertrigo-like eruption, hand and foot syndrome, toxic acral erythema, and others), and, even worse, by the histologic pattern (eg, eccrine squamous syringometaplasia, chemotherapyinduced epidermal dysmaturation, chemotherapy-induced neutrophilic eccrine hidradenitis, and others). Although most of the authors find the term TEC to be sufficiently appropriate and to allow for ease in communication with nondermatologists as well as reflecting the nonallergic and noninfectious nature of the eruption, other authors 24 do not. The chemotherapeutic agents most often associated with TEC are polyethelene glycol-coated liposomal doxorubicin, cytarabine, 5-fluorouracil, capecitabine, and docetaxel. The eruption usually appears 2 days to 3 weeks after the administration of chemotherapeutic agents. It might recur when the same or higher doses of chemotherapy is administrated. A delayed onset of up to several months can be seen in patients who are receiving lower doses of chemotherapeutic drugs. The main histologic feature of TEC—particularly the form that involves the intertriginous areas24—is eccrine squamous syringometaplasia, which is characterized by the transformation of the eccrine cuboidal epithelium into two or more layers of squamous cells with intercellular bridges. Other histologic findings25 are atypia (characterized by enlarged cell and nuclear size and nuclear pleomorphism) and apoptosis of keratinocytes, loss of polarity of epidermal cells and crowding of keratinocytes, vacuolar degeneration of the basal layer, and dermal edema. The exact pathogenesis of TEC remains unclear. One plausible explanation is that the chemotherapeutic agents that are excreted via eccrine sweat exert a toxic insult to the cells of the straight portion of the eccrine duct, the acrosyringium and the epidermis. The localization of the reaction could thus
Baboon syndrome and toxic erythema of chemotherapy be explained by the high density of eccrine glands on the palms and soles plus some occlusive phenomenon in intertriginous areas.26 Treatments of TEC remain nonspecific and primarily palliative. They include cool compresses, analgesics, bland emollients, topical corticosteroids, and topical antibiotics. Prevention of recurrence involves dose reduction, lengthening the interval between cycles, or discontinuation of the offending agents when possible. What is most essential, however, is early recognition of TEC, which may prevent the inappropriate use of systemic immunosuppressives for presumed hypersensitivity reaction or graft-versus-host disease or systemic antimicrobials for assumed infections.
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