The baboon syndrome or intertriginous drug eruption: a report of eleven cases and a second look at its pathomechanism

Although drug eruptions can mimic a variety of idiopathic skin diseases, this has not been mentioned in the differential diagnosis of intertrigo. We draw attention to an unusual presentation of a drug eruption with a characteristic distribution pattern that is confined to the intertriginous areas. This condition has been given one of the most memorable names in dermatology, the baboon syndrome. Originally, the baboon syndrome was described as a special form of systemic contact-type dermatitis (SCTD) that occurs after ingestion or systemic absorption of a contact allergen in individuals previously sensitized by topical exposure to the same allergen in the same areas. We present eleven cases of intertriginous eruptions that resulted from adverse drug reactions. A flare-up of a previous contact with the same allergen (i.e., drug) on the same areas is not a reasonable explanation for the unusual localization of the eruption in our and others' cases. We believe that we are dealing with a type of recall phenomenon and that the characteristic localization and appearance of the eruption is determined by an earlier, unrelated dermatitis that had occurred in precisely the same areas. Adverse drug reactions should always be considered in the differential diagnosis of intertrigo, especially in atypical and therapy-resistant cases.     

Baboon syndrome resulting from systemic drugs: is there strife between SDRIFE and allergic contact dermatitis syndrome?

The term 'baboon syndrome' (BS) was introduced 20 years ago to classify patients in whom a specific skin eruption resembling the red gluteal area of baboons occurred after systemic exposure to contact allergens. Thereafter, similar eruptions have been reported after systemic exposure to beta-lactam antibiotics and other drugs. In addition to the presentation of 2 of our own cases, we have reviewed and characterized the main clinical and histological aspects of published reports of drug-related baboon syndrome (DRBS) and compared the primary clinical signs from such cases to those found in other distinct drug eruptions. Of approximately 100 published baboon syndrome cases, 50 were identified as drug-induced. Of these, 8 were representatives of systemically induced contact dermatitis (SCD), and 42 were examples of drug eruptions elicited by systemic administration of either oral or intravenous drugs. The main clinical findings included a sharply defined symmetrical erythema of the gluteal area and in the flexural or intertriginous folds without any systemic symptoms and signs. 14 of 42 cases were elicited by amoxicillin, 30 of the 42 patients were male, and latency periods were between a few hours and a few days after exposure. DRBS is a rare, prognostically benign and often underdiagnosed drug eruption with distinct clinical features. The term baboon syndrome, however, does not reflect the complete range of symptoms and signs and is ethically and culturally problematic. Moreover, baboon syndrome is historically often equated with a mercury-induced exanthem in patients with previous contact sensitization. Symmetrical drug-related intertriginous and flexural exanthema, or SDRIFE, specifically refers to the distinctive clinical pattern of this drug eruption, and the following diagnostic criteria are proposed: 1) exposure to a systemically administered drug either at the first or repeated dose (excluding contact allergens); 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 localization; 4) symmetry of affected areas; and 5) absence of systemic symptoms and signs.     

Occupational facial allergic contact dermatitis caused by Finnish pine and spruce wood dusts

The term baboon syndrome was introduced 20 years ago. It was proposed for a particular eruption mimicking the red gluteal area of the baboon after systemic exposure either to the contact allergens nickel and mercury or to oral ampicillin. Previously this phenomen was e.g. termed flexural exanthema to mercury. Since then similar incidences have been reported after systemic exposure to betalactam antibiotics and other drugs, sometimes under different terms. Clinically sharp demarcation of a V‐shaped erythema is present in inguinal/genital and gluteal/perianal areas. Additionally papules, vesicles and hemorrhagic lesion may be found. In most patients presence of exanthema in other anatomical flexural regions (axilla, elbow, knee, ventral neck) has been identified. However, involvement of the plantar/palmar regions, face and mucosal sites has not been documented. Typically blood tests are normal and systemic symptoms are absent. Histological results vary but a predominance of superficial perivascular infiltrate with mononuclear cells has been reported. Occasional positive patch tests or stimulation of lymphocytes in the LTT may be suggestive for a type IV allergic reaction. Since the drug‐related baboon syndrome shows clinically and histologically different findings to systemic contact dermatitis and acute generalized exanthematous pustulosis (AGEP), it should be seen as a separate entity. The mainstay for the diagnosis of systemic contact dermatitis requires contact sensitization and elicitation by a contact allergen. In contrast in the baboon syndrome and AGEP history for sensitization is often negative, although sometimes positive patch and LTT results can be found. AGEP, on the other hand, requires a distinct score including systemic signs and leucocytosis. In all three symptoms typically occur within 1 to 2 days. The term baboon syndrome does not reflect the whole range of symptoms and signs. And, although it is easily remembered, the comparison to an animal may be insulting. Therefore, we suggest that drug‐induced baboon syndrome should be separated from the contact allergen‐induced form, and should be recognized as a separate entity within the spectrum of drug eruptions. For this reason we propose the acronym SDRIFE (symmetrical drug related intertriginous flexural exanthema). This refers to the distinctive clinical pattern of this drug eruption without implicating any pathomechanism, which has not been clearly elucidated. The following criteria are proposed: 1) Exposure to a systemically administered drug, 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) Bilaterally or symmetrically affected areas, and 5) Absence of systemic symptoms and signs.     

Symmetrical drug-related intertriginous and flexural exanthema secondary to topical 5-fluorouracil

We report the case of a 56-year-old man who developed a distinctive skin eruption after treating actinic keratoses on the dorsal aspects of his right and left hands with topical 5-fluorouracil (5-FU). The distribution of his rash was characteristic of symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), also known as baboon syndrome.     

Symmetrical Drug-Related Intertriginous and Flexural Exanthem due to Oral Risperidone

Abstract:   We report the case of an 8-year-old boy who developed a distinctive skin eruption after oral treatment with risperidone for the syndrome of attention deficiency with hyperactivity. The clinical findings were compatible with so-called symmetrical drug related intertriginous and flexural exanthema, also known as Baboon syndrome. Although epicutaneous patch testing with the offending drug was negative, drug rechallenge produced a recurrence of the skin findings. To the best of our knowledge, this is the first case of symmetrical drug related intertriginous and flexural exanthema reported due to risperidone.     

Intertriginous eruption

Intertrigo is a superficial inflammatory skin disorder involving any area of the body where two opposing skin surfaces can touch and rub or chaff. The word “intertrigo" comes from the Latin inter (between) and terere (to rub) and reflects the rubbing together of skin against skin to create maceration and irritation, hence, friction dermatitis or chaffing. It is a common disorder that can affect any individual from infancy to old age. It is primarily caused by skin-on-skin friction and is facilitated by moisture trapped in deep skin folds where air circulation is limited. The condition is particularly common in obese patients who have diabetes and who are exposed to heat and humidity. The moist, damaged skin associated with intertrigo is a fertile breeding ground for various microorganisms, and secondary cutaneous infections are commonly observed in these areas. The present chapter does not deal with “ordinary" intertrigo, but rather with other skin diseases that have affinity to the intertriginous areas. Diseases mentioned are: acrodermatitis enteropathica, the baboon syndrome or intertriginous drug eruption, Darier disease, Hailey-Hailey, granular parakeratosis, Kawasaki syndrome, necrolytic migratory erythema, streptococcal intertrigo and others.     

A Systematic Approach to Systemic Contact Dermatitis and Symmetric Drug-Related Intertriginous and Flexural Exanthema (SDRIFE)

Systemic contact dermatitis is a condition that occurs when an individual sensitized to a contact allergen is exposed to that same allergen or a cross-reacting molecule through a systemic route. Systemic exposure to allergens can include transcutaneous, transmucosal, oral, intravenous, intramuscular, and inhalational routes. Baboon syndrome is perhaps the most recognizable form of systemic contact dermatitis, presenting with diffuse, well demarcated erythema of the buttocks, upper inner thighs, and axillae. Other forms of systemic contact dermatitis include dermatitis at sites of previous exposure to the allergen such as at a previous site of dermatitis or at sites of previous positive patch tests, dyshidrotic hand eczema, flexural dermatitis, exanthematous rash, erythroderma, and vasculitis-like lesions. The most common causes of systemic contact dermatitis consist of three groups of allergens: (i) metals including mercury, nickel, and gold; (ii) medications including aminoglycoside antibacterials, corticosteroids, and aminophylline; and (iii) plants and herbal products including the Compositae and Anacardiaceae plant families and Balsam of Peru. Baboon syndrome caused by systemic medications without a known history of previous cutaneous sensitization in the patient has been termed drug-related baboon syndrome (DRBS) or symmetric drug-related intertriginous and flexural exanthema (SDRIFE). Criteria for SDRIFE include exposure to systemic drug at first or repeated dose, erythema of the gluteal/perianal area and/or V-shaped erythema of the inguinal area, involvement of at least one other intertriginous localization, symmetry of affected areas, and absence of systemic toxicity. The most common causes are aminopenicillins, β-lactam antibacterials, and certain chemotherapeutic agents, though the list of etiologic agents continues to grow. Baboon syndrome and SDRIFE should be strongly considered in a patient presenting with a symmetric intertriginous eruption involving multiple body folds. With the knowledge of the most frequent causes of these conditions, a detailed history and review of exposures will guide the clinician in the search for the most likely etiologic agent.     

Giant cell lichenoid dermatitis in a patient with baboon syndrome

Giant cell lichenoid dermatitis is a recently described pathological entity, which can be seen as an unusual lichenoid drug eruption, a manifestation of sarcoidosis or within herpes zoster scars. Histopathological findings include focal vacuolar alteration of the basal layer with cytoid bodies, dermal and intraepidermal multinucleated giant cells and a mixed chronic inflammatory infiltrate with a lichenoid pattern consisting of lymphocytes, histiocytes, eosinophils and plasma cells. Here, we report a giant cell lichenoid dermatitis in a 41-year-old male patient who developed, 3 days after intravenous treatment with amoxicillin-clavulanic acid for erysipelas of the left leg, a clinical picture suggesting a baboon syndrome characterized by an erythematous and pruritic eruption on the axillary, inguinal and popliteal areas and the anterior side of elbows. This is the first reported case of giant cell lichenoid dermatitis in a patient with baboon syndrome.     

Granulomatous and eccrinotropic lymphomatoid papulosis

Lymphomatoid papulosis has been classically described as a chronic, recurrent and self-healing papulonecrotic or papulonodular skin eruption, which is clinically benign and histopathologically malignant. The histologic characteristics of lymphomatoid papulosis are suggestive of a cluster of differentiation 30+ (CD30+) malignant lymphoma, and it is best regarded as a low grade cutaneous T cell lymphoma (CTCL). We hereby report a case of granulomatous and eccrinotropic lymphomatoid papulosis in a 40- year-old male. There was no systemic involvement. The patient was treated with low dose oral methotrexate with good response.     

Lymphomatoid drug eruption mimicking digitate dermatosis: cross reactivity between two drugs that suppress angiotensin II function

A 75-year-old male presented with an eruption characteristic of digitate dermatosis. The eruption cleared completely after discontinuation of lisinopril (angiotensin converting enzyme inhibitor). Eighteen months later a similar eruption recurred after using valsartan (a competitive inhibitor of angiotensin II receptor). The eruption cleared after discontinuation of valsartan. Histologic findings in both eruptions were consistent with lymphomatoid drug eruption. This case is interesting in that the eruption occurred after the intake of two structurally unrelated drugs that interfere with angiotensin II function. This observation may shed light on the mechanisms that may be operative in provoking the lymphomatoid drug eruption.     

A case of lymphomatoid papulosis with prominent myxoid change resembling a mesenchymal neoplasm

Lymphomatoid papulosis is a chronic recurrent eruption of self-regressing papules and nodules. Histologically this disorder is characterized by large atypical lymphoid cells resembling Reed-Sternberg (RS) cells that are set in a background of a mixed inflammatory infiltrate. Depending on the architecture of the infiltrate and the percentage of atypical cells, the histologic appearance is subclassified as type A, B, or C. The different histologic patterns do not seem to correlate with distinct clinical appearances. We report a case of lymphomatoid papulosis with unusual histologic features affecting a 14-year-old girl. The presence of anaplastic cells in a background of myxoid stroma closely resembled a sarcoma on histologic examination.     

Eosinophilic histiocytosis: A variant form of lymphomatoid papulosis or a disease sui generis?

Five patients are reported on whose clinical skin disease consisted of polymorphous papulonodular lesions healing with a depigmented scar. Although all cases had been termed lymphomatoid papulosis after clinical or histologic examination, the lesions consisted principally of masses of histiocytes and eosinophils. Individual lesions healed spontaneously or with minimal treatment, but the chronic course of disease was not altered by any therapy used. Follow-up 3 to 17 years later indicated persistent or recurrent disease, and one patient died of histiocytic malignancy. Eosinophilic histiocytosis is the microscopic picture of an unusual group of patients with chronic papulonodular necrotic skin disease that may deserve to be considered a disease pattern per se.     

A Challenging Case: Symmetrical Drug Related Intertriginous and Flexural Exanthem,Fixed Drug Eruption,or Both?

Abstract: We herein report a 12‐year‐old boy with amoxicillin‐induced, recurrent, site‐specific, symmetrical, sharply demarcated reddish plaques on the buttocks and the major flexural and intertriginous areas. The lesions resolved with topical corticosteroids, leaving hyperpigmentation. Histopathology showed nonspecific features of inflammation and dermal melanophages. Amoxicillin was the probable inducer based on oral provocation test with Amoksina^® tablet, however patch testing with amoxicillin on previously affected and unaffected skin remained negative. The diagnosis was challenging because of the overlapping features of symmetrical drug‐related intertriginous and flexural exanthema and fixed drug eruption. This one represents a unique and challenging one with overlapping clinical features of symmetrical drug‐related intertriginous and flexural exanthem (SDRIFE) and fixed drug eruption (FDE). We discuss the possible immunopathogenetic mechanisms leading to the simultaneous occurrence of different phenotypes of drug eruption in the same patient.     

Intertriginous drug eruption.

Presented are two patients who developed an unusual, and as yet unreported eruption due to amoxycillin. They exhibited an eruption confined to the intertriginous areas, which mimicked intertrigo. Although drug eruption can mimic a variety of idiopathic skin diseases, intertrigo is easily distinguished from drug eruption and has not been mentioned in the differential diagnosis of this reaction. It is suggested that drug reactions should be considered in the differential diagnosis of intertrigo, in particular of atypical and therapy-resistant cases. Early detection of these cases has practical importance since the elimination of the causative drug is essential for therapy success. Case 2 showed a response of the toxic epidermal neurolysis (TEN) type, which could have been very severe and dangerous had the diagnosis not been made in an early stage before the development of generalized TEN.     

Neutrophilic pustulosis and ulcerative colitis

Neutrophilic pustulosis is currently considered as a part of the spectrum of Sweet's syndrome, and has been associated with inflammatory bowel disease and several other diseases. We report the case of a 34-year-old male who had been suffering from ulcerative colitis (UC) for several years and who experienced the manifestation of a pustular eruption on both forearms and the abdominal wall during an exacerbation of his bowel disease. Both processes were controlled with steroids per os. The histological picture showed an inflammatory infiltrate composed mainly of neutrophils with scattered neutrophilic epidermal abscesses. Certain distinct clinical and histological characteristics have been described as diagnostic of the pustular eruption of UC. This picture should be included in the spectrum of the neutrophilic dermatosis, in our case associated with an ulcerative colitis. This is a well documented clinical and histologic case report of a recognized association of inflammatory pustulosis in the course of ulcerative colitis.     

Ethosuximide‐induced Stevens–Johnson syndrome: Beneficial effect of early intervention with high‐dose corticosteroid therapy

We report two rare cases of childhood epilepsy patients who developed ethosuximide‐induced Stevens–Johnson syndrome (SJS). Unlike typical SJS, the initial eruption of both patients presented well‐demarcated, infiltrating firm papules mainly on the cheeks and the extensor aspects of the arms (case 1), and multiple vesicles on the soles and oral aphthosis (case 2), which closely mimicked viral exanthema. We diagnosed both patients with ethosuximide‐induced SJS, based on the dosing period and the positive results of drug‐induced lymphocyte stimulation test. Systemic corticosteroids are usually selected as a standard therapy for SJS, despite controversial results regarding their effectiveness. In case 1, an i.v. pulse therapy of methylprednisolone (30 mg/kg, 3 days consecutively) was initiated on day 7 from the onset of illness, and an i.v. immunoglobulin (400 mg/kg, 5 days consecutively) was added the following day. In case 2, an i.v. prednisone treatment (1 mg/kg, for 1 week) was initiated on day 4 from the onset. Eventually, the early therapeutic interventions resulted in good outcomes in both patients.     

Complicated lichenoid drug eruption

We report a case of severe lichenoid drug eruption with multiple possible causative agents. A hepatitis C-positive male presented with a short history of painful erosions of the vermilion, lichenoid lesions on the buccal mucosa and glans penis, and erosions and lichenification of the scrotum. In addition, he had a pruritic polymorphic eruption over the scalp, trunk and limbs, comprising psoriasiform and eczematous lesions. He had received combination therapy of pegylated interferon-alpha-2a and ribavirin, along with granulocyte colony-stimulating factor for interferon-induced leucopenia, and propranolol for portal hypertension. The former three agents were ceased 3 weeks prior to presentation, but he remained on propranolol at the initial dermatology consultation. The polymorphous clinical picture was consistent with lichenoid drug eruption, which was confirmed on histology. The papulosquamous eruption responded quickly to 2 weeks of oral prednisone 25 mg daily, which was tapered to 1 mg over 3 months and then ceased. The mucosal lesions were slow to improve and required the addition of tacrolimus 0.03% solution t.d.s. for complete resolution.     

Amoxycillin-induced flexural exanthem

We describe a 37-year-old man who developed an acute, inflammatory flexural eruption shortly after taking amoxycillin, then erythema multiforme-like lesions on the palms and soles. The eruption resolved with systemic corticosteroids, and positive patch tests with amoxycillin supported a drug-induced aetiology. A few similar cases have been described as the 'baboon syndrome' or intertriginous drug eruptions. We draw attention to this rare, distinctive drug eruption.     

Mucosal involvement in lymphomatoid papulosis: four cases

BACKGROUND: Lymphomatoid papulosis is a form of CD30+ cutaneous lymphoproliferation characterized by a benign chronic papulonodular eruption that regresses spontaneously. The clinical features contrast with the malignant histological aspect of lesions. Mucosal lesions are rare, with less than 10 published cases. We report four new cases and we highlight characteristic features of lesions at this particular site. PATIENTS AND METHODS: We report four cases of mucous lymphomatoid papulosis in three women aged 37, 38, and 71 years and one 66-year-old man. These cases were collated from three different hospitals: Orléans, Rouen and Caen. Mucosal lesions occurred after cutaneous eruption in two cases but remained isolated or preceded cutaneous lesions in the other two cases. The main site was the mouth in all four cases but one case also involved genital lesions. Two cases involved type A pathological features and two had type C features. Association with lymphoma was excluded on clinical, laboratory and radiological examination. One patient was treated with methotrexate (>7.5mg/week) and did not relapse. Of the three other untreated patients only one did not relapse (short 14-month follow-up). DISCUSSION: Recurrent oral ulcerations may be mucosal manifestations of lymphomatoid papulosis. This site does not appear to have any bearing on prognosis.     

Histopathologic studies in Sézary syndrome and erythrodermic mycosis fungoides: a comparison with benign forms of erythroderma

Histologic sections from eleven patients with Sézary syndrome were reviewed and compared with those of four patients with erythrodermic mycosis fungoides and twenty-four patients with a benign form of erythroderma, including fifteen patients with chronic dermatitis, four with a generalized drug eruption, and five with an erythrodermic psoriasis. The most important discriminating histologic feature in patients with Sézary syndrome was the presence of a monotonous bandlike or perivascular infiltrate in the papillary dermis, mainly composed of large cerebriform-mononuclear cells, as seen in seven of eleven Sézary syndrome patients. Pautrier's microabscesses were observed in seven of eleven Sézary syndrome patients, two of four patients with erythrodermic mycosis fungoides, but not in any of the patients with a benign form of erythroderma; their presence was therefore considered a reliable criterion in differentiating erythrodermic cutaneous T cell lymphoma from benign forms of erythroderma. However, features of chronic dermatitis were often found superimposed on those of Sézary syndrome and were even predominating in four of eleven Sézary syndrome patients. Moreover, four patients with a benign form of erythroderma showed a histologic picture suggestive of cutaneous T cell lymphoma. Therefore, in dubious cases repeated skin biopsies, additional investigations of lymph nodes and peripheral blood, and careful follow-up are mandatory for the achievement of a correct diagnosis.