Symmetric drug-related intertriginous and flexural exanthema: Clinicopathologic study of 19 cases and review of literature.

BACKGROUND: Symmetric drug-related intertriginous and flexural exanthema (SDRIFE) is a cutaneous drug reaction characterized by gluteal/anogenital erythema and symmetric involvement of other intertriginous location(s) without systemic signs. Clinicopathologic characterization has been limited to case reports and small series. We describe 19 new cases and review the literature to better define the clinical and histopathologic spectrum of SDRIFE. METHODS: Pathology archives were searched for "SDRIFE" and "baboon syndrome." Cases meeting clinical criteria were included. Clinical and histopathologic features were recorded. Previous reports of SDRIFE with histopathologic descriptions were reviewed. RESULTS: Nineteen new cases were included, over half triggered by antibiotics. Six new causative medications were identified. Median onset was 7 days. Typical lesions were erythematous plaques or papules with or without scale. The most common histopathologic finding was superficial perivascular lymphocytic infiltrate followed by dermal eosinophils, spongiosis, and orthokeratosis. Basal vacuolization and apoptotic keratinocytes were less common. Interstitial histiocytes were present in almost half of our cases. Other findings included atypical lymphocytes and "flame figure." CONCLUSIONS: Appreciation of the range of inciting medications and clinicopathologic features in SDRIFE will improve recognition of this condition. Although many histopathologic features overlap with other common dermatitides, biopsy may assist in excluding key clinical mimics.

Thiotepa hyperpigmentation preceding epidermal necrosis: malignant intertrigo misdiagnosed as Stevens-Johnson syndrome-toxic epidermal necrolysis overlap.

Thiotepa is a common alkylating agent known to precipitate cutaneous reactions consistent with toxic erythema of chemotherapy, including erythema and hyperpigmentation. Herein, we describe an atypical case of malignant intertrigo involving preferential erythema and desquamation not only of skin folds but also of occluded areas after thiotepa-based conditioning. The diagnosis was complicated by concurrent stomatitis and oral petechiae in the setting of autologous stem cell transplant 11 days prior for diffuse large B-cell lymphoma. Histopathological examination from two cutaneous sites demonstrated epidermal dysmaturation and eccrine gland necrosis consistent with thiotepa-induced desquamation and not Stevens-Johnson syndrome or graft-versus-host-disease. Malignant intertrigo can present with extensive cutaneous involvement, as evidenced by our patient who had 25% body surface area affected. Mucosal involvement is common with most chemotherapeutic regimens and its presence should not deter the astute clinician from consideration of a diagnosis of toxic erythema of chemotherapy. No further interventions were needed and the patient healed spontaneously.

[Fatal outcome of Netherton syndrome due to excessive use of topical corticosteroids in an adult patient]. / Évolution fatale du syndrome de Netherthon due à une utilisation excessive de dermocorticoïdes chez un adulte.

INTRODUCTION: Netherton syndrome (NS) is a rare disease caused by SPINK5 mutations associated with ichthyosis (erythroderma and desquamation), alopecia and atopic manifestations. There are no effective treatments. Topical corticosteroids may be used for a limited period in the event of eczema. Herein we report on a patient with fatal complications related to misuse of topical corticosteroids. PATIENTS AND METHODS: A 38-year-old woman with NS had been using betamethasone for about ten years for severe pruritus. Consumption was estimated at 7.2kg per year. On examination, she had osteoporosis, Cushing's syndrome, corticotropic insufficiency and inframammary, axillary, and intergluteal superinfected intertrigo. During hospitalization for necrotic leg wounds on severe skin atrophy, she sustained a fracture on falling down. The course was marked by the onset of septic shock of unknown etiology, complicated by acute adrenal insufficiency leading to fatal multi-organ failure. DISCUSSION: Many iatrogenic cases related to topical corticosteroids in children have been reported in the literature, including one case of fatal outcome (CMV infection) in an infant. Such iatrogenic cases are rarer in adults and we observed no fatal cases. In NS, the adverse effects of topical corticosteroids are amplified due to the major defect in the skin barrier which enhances the systemic passage of these drugs. In the absence of any effective therapeutic alternative, weaning patients off topical corticosteroids is usually difficult. CONCLUSION: This case illustrates the severity of iatrogenic effects secondary to misuse of topical corticosteroids in NS as well as the need to find effective new treatments for this syndrome.

Symmetrical drug-related intertriginous and flexural exanthema due to clindamycin.

Systemic drug exposure can produce a skin reaction consisting of symmetrical erythema involving the gluteal and intertriginous areas in the absence of systemic involvement. Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) occurs after systemic exposure to a drug in which the patient was not previously sensitised, either in the first dose or after several doses. The mechanism of SDRIFE is unknown but is hypothesised to be the result of a delayed hypersensitivity response resulting in a cutaneous eruption some days after the exposure to the drug. The diagnosis should be clinical, based on the history and examination, but skin tests can also be performed to confirm sensitisation. But, as always, the gold-standard test is oral provocation. It is important to know this clinical entity to prevent re-exposure to the responsible allergen in the future.

Case of severe bullous erythema including intertrigo-like eruptions with angioedema induced by pegylated liposomal doxorubicin.

Pegylated liposomal doxorubicin (PLD) is an anthracycline anticancer agent used in ovarian cancer and a form of doxorubicin enclosed in pegylated liposomes. There are only a few reports on intertrigo-like eruptions caused by PLD. We describe the first case of severe bullous erythema, including intertrigo-like eruptions with angioedema, induced by PLD in Japan. We present the case of a 53-year-old woman who was diagnosed with stage IIIC ovarian cancer. After receiving three cycles of PLD, the patient developed swelling of the upper lip and painful erythema with blisters and erosions on the axilla, upper back, flank and wrists. The patient was diagnosed with angioedema and severe skin lesions, including intertrigo-like eruptions induced by PLD. Although treatment with oral prednisolone and topical steroids was effective against these eruptions, the administration of PLD was discontinued because of its ineffectiveness against the primary disease. Several risk factors, such as obesity, perspiration and racial differences, may contribute toward a severe manifestation such as that seen in our patient. Moreover, our case was the first accompanied by angioedema. The mechanism of coexistence of intertrigo-like eruptions and angioedema is not clear; further studies are required to clarify the pathological mechanism of intertrigo-like eruptions.

Dermatosis intertriginosa crónica de aparición tardía: pénfigo de Hailey-Hailey / Chronic late-onset intertriginous dermatitis: Hailey-Hailey's pemphigus

El pénfigo familiar benigno o enfermedad de Hailey Hailey, es una genodermatosis vesico-ampollar autosómica dominante, con penetrancia incompleta y expresividad variable de presentación infrecuente. Se presenta el caso de un paciente con un cuadro de cinco años de evolución, caracterizado por lesiones vesiculares intertriginosas, de olor desagradable, con mala respuesta al tratamiento tópico con antifúngicos y corticoides. Se realiza biopsia de piel compatible con pénfigo de Hailey Hailey, el que fue manejado con antibióticoterapia y corticoides sistémicos, evolucionando favorablemente.

The benign familial pemphigus or Hailey Hailey´s disease is a rare autosomal dominant disorder. We present the clinical case of a patient with a five years history, characterized by vesicular intertriginous malodorous lesions with poor response to topical antifungal therapy. Skin biopsy it was compatible with Hailey Hailey´s disease which was managed with antibiotic therapy and systemic corticosteroids. The patient evolved favorably.

Successful treatment of recalcitrant candidal intertrigo with Dr Michaels® (Fungatinex®) product family.

Candidal intertrigo is an infection of the skin caused by Candida albicans that typically occurs in opposing cutaneous or muco-cutaneous surfaces. Because Candidiasis requires a damaged and moist environment for infection, it typically occurs in areas of friction such as the skin folds of the body. Candidal intertrigo is often difficult to treat and results are often unsatisfactory. In addition, there is a lack of evidence-based literature supporting prevention and treatments for candidal intertrigo. The aim of the study was to evaluate the efficacy of Dr Michaels® (also branded as Fungatinex®) products in the treatment of fungal intertrigo, in 20 women and 2 men with a mean age of 72. Five patients (3 female and 2 male) had type 2 diabetes and 16 (14 female and 2 male) were obese. The patients were treated with Dr Michaels® (Fungatinex®) moisturising bar, topical ointment (twice daily application) and oral herbal formulation, PSC 200 two tablets twice daily with food. After 2 weeks of treatment, the lesions had mostly resolved in all patients with only slight erythema evident. After six weeks of treatment using the moisturising bar, topical ointment and oral herbal formulations from the Dr Michaels® (Fungatinex®) product family, the lesions had totally resolved in 18 patients, while 4 patients had to continue the therapeutic protocol for another 2 weeks. Our results demonstrate that the Dr Michaels® (Fungatinex®) complementary product family is efficacious in the treatment of recalcitrant candidal intertrigo. Furthermore, this study highlights that the Dr Michaels® (Fungatinex®) product family is fast-acting and well tolerated with no serious adverse events reported. These data have important implications for resistant cases of candidal intertrigo where traditional therapies have failed.

Hailey-Hailey disease: A fold (intertriginous) dermatosis.

Hailey-Hailey disease, also called benign familial pemphigus, is a late-onset blistering disorder that affects the flexures. There are typically painful erosions and cracks in affected areas. Lesions generally begin between 20 and 40 years of age. In two third of all cases, positive family history is detected. In pathogenesis, there is a defect in keratinocyte adhesion due to ATP2 C1 gene mutation. The result of the desmosomal decomposition is acantholysis. Menstruation, pregnancy, skin infections, physical trauma, excessive sweating and exposure to ultraviolet radiation are important triggering factors. Histopathologic changes are suprabasal acantholysis and formation of intraepidermal bullae. In the epidermis, a partial acantholysis that looks like broken bricks is observed.

Psoriasis inversa: A separate identity or a variant of psoriasis vulgaris?

Psoriasis is a chronic skin disorder affecting approximately 2% of the European and American population. The most common form of psoriasis is the chronic plaque type. Inverse psoriasis, also named flexural or intertriginous psoriasis, is not considered a separate disease entity but rather a special site of involvement of plaque psoriasis, characterized by its localization to inverse/intertriginous/flexural body sites. We review current evidence and establish whether inverse psoriasis is a separate disease entity based on characteristics in terms of epidemiology, pathogenesis, clinical and histologic presentation, microbiology, and treatment.

Acanthosis nigricans: A fold (intertriginous) dermatosis.

Acanthosis nigricans (AN) is a mucocutaneous disorder that is characterized by focal or diffuse hyperkeratotic, surfaces, which are symmetrically distributed hyperpigmented lesions of the skin. It rarely affects mucosal surfaces like oral cavities. Although it is commonly seen in adolescents, AN is also increasingly seen in children who are obese. Recent studies have found that AN can be a cutaneous indicator of insulin resistance and malignancy. Acanthosis nigricans has been associated with type 2 diabetes mellitus, obesity, endocrinopathies, drugs, and malignancies.

Pemphigus vegetans of the folds (intertriginous areas).

Pemphigus vegetans (P Veg), the rarest form of pemphigus, is thought to be a variant of pemphigus vulgaris (PV). Classically, two subtypes of P Veg are recognized: (1) Neumann P Veg, which usually begins as PV with vesicles and bullae that rupture to form hypertrophic granulating erosions, then evolving into vegetating exuding masses; (2) Hallopeau P Veg, initially characterized by pustular lesions that, after rupturing, merge and gradually evolve into vegetating erosions with a centrifugal expansion. The disease typically affects the big folds (axillary, inframammary, inguinocrural, intergluteal), where semiocclusion, maceration, and mixed infections continuously incite exudation and granulation tissue formation (wet P Veg). In nonintertriginous locations, the vegetating buttons can dry out to change into warty, fissured, painful, seborrheic keratosis-like lesions (dry P Veg). Histologic examination indicates hyperplastic epidermis with intramalpighian leukocyte microabscesses and indistinct traits of suprabasal acantholysis. Immunofluorescence findings are similar to those of PV. Diagnosis is straightforward when PV lesions coexist. Difficulties can arise in cases with nonflexural location. Cytology (Tzanck test), histology, immunofluorescence, and ELISA search for anti-desmoglein antibodies are the diagnostic laboratory tools. Systemic treatment is similar to that for PV, high-dose steroids being the first choice therapy. Immunosuppressive agents and etretinate may allow a steroid-sparing effect. Topical treatment is aimed at countering the granulation tissue formation by means of several strategies (sublesional steroid injection, application of medicated gauzes in the involved flexures, chemical cautery or surgical excision of vegetating lesions).

Diaper (napkin) dermatitis: A fold (intertriginous) dermatosis.

Diaper (napkin) dermatitis is an acutely presenting inflammatory irritant contact dermatitis of the diaper region. It is one of the most common dermatologic diseases in infants and children. In the past, the disease was thought to be caused by ammonia; however, a number of factors, such as friction, wetness, inappropriate skin care, microorganisms, antibiotics, and nutritional defects, are important. Diaper dermatitis commonly affects the lower parts of the abdomen, thighs, and diaper area. Involvement of skin fold regions is typical with diaper dermatitis. At the early stages of the disease, only dryness is observed in the affected area. At later stages, erythematous maceration and edema can be seen. Secondary candidal and bacterial infections can complicate the dermatitis. In the differential diagnosis of the disease, allergic contact dermatitis, intertrigo, psoriasis, atopic and seborrheic dermatitis, and the other diseases should be considered. Causes of the disease should be determined and eliminated primarily. Families need to be informed about the importance of a clean, dry diaper area and the frequency of diaper changes. The use of superabsorbent disposable diapers has decreased the incidence of the disease. Soap and alcohol-containing products should be avoided in cleaning the area. In some cases, corticosteroids and antifungal agents can be administered. If necessary, antibacterial agents and calcineurin inhibitors can also be beneficial.

Hyperhidrosis, bromhidrosis, and chromhidrosis: Fold (intertriginous) dermatoses.

Human sweat glands disorders are common and can have a significant impact on the quality of life and on professional, social, and emotional burdens. It is of paramount importance to diagnose and treat them properly to ensure optimal patient care. Hyperhidrosis is characterized by increased sweat secretion, which can be idiopathic or secondary to other systemic conditions. Numerous therapeutic options have been introduced with variable success. Novel methods with microwave-based and ultrasound devices have been developed and are currently tested in comparison to the conventional approaches. All treatment options for hyperhidrosis require frequent monitoring by a dermatologist for evaluation of the therapeutic progress. Bromhidrosis and chromhidrosis are rare disorders but are still equally disabling as hyperhidrosis. Bromhidrosis occurs secondary to excessive secretion from either apocrine or eccrine glands that become malodorous on bacterial breakdown. The condition is further aggravated by poor hygiene or underlying disorders promoting bacterial overgrowth, including diabetes, intertrigo, erythrasma, and obesity. Chromhidrosis is a rare dermatologic disorder characterized by secretion of colored sweat with a predilection for the axillary area and the face. Treatment is challenging in that the condition usually recurs after discontinuation of therapy and persists until the age-related regression of the sweat glands.