Marco Ardigò

Muco-cutaneous changes during long-term therapy with hydroxyurea in chronic myeloid leukaemia

Hydroxyurea is an antimetabolite agent used in the treatment of myeloproliferative disorders and sickle cell anaemia. Although hydroxyurea is relatively well tolerated, adverse effects often involve skin and mucous membrane during long‐term therapy. A group of 510 patients affected by chronic myeloid leukaemia from 1977 to 1998 has been considered. Only 158 patients were treated with hydroxyurea and fulfilled inclusion/exclusion criteria of this study. A spectrum of severe cutaneous and mucosal changes (inflammatory and neoplastic) was seen in about 13% of patients (21 patients out of 158) and was studied in detail. Cutaneous and mucosal atrophy were observed in all 21 patients. Skin atrophy was often characterized by numerous telangiectases, especially on legs and on sun‐exposed sites (16/21). Cutaneous, mucosal and nail hyperpigmentation was evident, albeit with variable extent, in 10 of the 21 patients. Severe stomatitis and glossitis with flattening of papillae were another common finding. Five patients, who received a particularly long treatment with hydroxyurea, developed squamous‐cell neoplasms on sun‐exposed sites (both squamous‐cell carcinomas and keratoacanthomas). Acral changes were characteristic and constant, including acral erythema (21/21), dermatomyositis‐like changes on the dorsa of hands (7/21), ulcers localized on acral areas of legs, on genitalia and oral mucosae (20/21). The frequency and the variety of these muco‐cutaneous changes are reported and the mechanisms by which hydroxyurea may induce this muco‐cutaneous syndrome‐like group of changes, are proposed.

Radiation recall dermatitis, panniculitis, and myositis following cyclophosphamide therapy: histopathologic findings of a patient affected by multiple myeloma.

Radiation recall dermatitis is one of the skin sequelae that may affect oncology patients. It occurs in a previously irradiated field, when subsequent chemotherapy is given. The eruption may be elicited by chemotherapy, even several months after radiotherapy. Its mechanism is poorly understood, and the histopathologic findings have received, to date, only sketchy descriptions. A 55-year-old male affected by multiple myeloma received radiation therapy both on his left coxofemoral area, and lumbar region (D11-L1). After cyclophosphamide administration, he developed 2 well defined square-shaped, infiltrated erythematoviolaceous plaques in the prior irradiated fields. Histopathologic findings revealed a diffusely fibrosclerosing process, involving deep dermis, hypodermis, as well as the underlying muscle, while sparing the epidermis and superficial-mid dermis. Histopathology was indistinguishable from deep radio-dermatitis, panniculitis, and myositis. This is the first case providing clear evidence of the causative role of cyclophosphamide in inducing a cutaneous and subcutaneous radiation recall reaction.

Exaggerated Insect Bite-like Reaction in Patients Affected by Oncohaematological Diseases

Sir,Patients affected by chronic B-cell lymphatic leukaemia(CBLL) and, more rarely, other oncohaematologicaldiseases may present with papules, plaques, nodules andvesico-bullous lesions on exposed areas (1–3). Theselesions are usually considered an exaggerated reaction toinsect bites, although the patients not always had ahistory (except for the seasonal presentation of cuta-neous findings), the clinical picture, and response totreatment suggestive of insect bite (3, 4). This phenom-enon has been described in about 40 patients affected bylymphoproliferative disorders, 95% of whom had CBLL(1–7). Weed (1) first gave the definition of ‘exaggerateddelayed hypersensitivity to mosquito bites’ and reportedthis condition only in patients affected with CBLL.Later, Houston & Keene (2) described a case ofexaggerated insect bite-like reaction also in a patientwith lymphocytic lymphoma. In 1986, Rosen et al. (3)studied 10 patients and suggested that the cutaneouslesions could be linked, in some way, to the onco-haematological conditions, without explaining the exactpathway.Five patients affected by different B lymphoprolifera-tive disorders, who presented with pruritic papules,nodules and vesico-bullous lesions on exposedareas during spring and summer time, are reported.We discuss an immuno-allergic mechanism, involvingboth allergic reaction to insect bite and the impair-ment of the immune response in oncohaematologicalpatients.CASE REPORTSFrom 1995 to 2001, three patients affected by CBLL andtwo by non-Hodgkin B-cell lymphomas attended ourdepartment with polymorphous, erythematous cuta-neous papules and plaques, some of them evolving intobullous lesions. During spring-summer all the patientsdeveloped very itchy lesions, plaques (Fig. 1) andsometimes bullae, mainly localized on upper and/orlower limbs and on the face. Three patients referred tohave been bitten by mosquitoes, the other two deniedthis occurrence. At the time of the clinical examination,all the patients were living in or close to the area ofPavia, Italy, where seasonal infestations of mosquitoes(Aedes) are particularly widespread. All the patientsunderwent a 4-mm punch biopsy, necessary for ahistopathologic evaluation; a direct immunofluores-cence test was carried out for four patients, to excludeautoimmune bullous diseases.At the time of the eruption, one patient was ontreatment with VACOP-B protocol (adriblastina, cyclo-phosphamide, etoposide, vincristine, bleomycin, predni-sone), two patients with chlorambucil and one withcyclophosphamide. An 87-year-old patient was notunder treatment. Blood analysis revealed peripheraleosinophilia in three patients out of five. Stool analysissearching for parasites was carried out in those threepatients and proved negative. IgE was in the normalrange in all the patients. Serum protein electrophoresisrevealed that total immunoglobulins were in the normalrange or little lower in all the patients, while all of thempresented a different degree of decrease of IgG, IgMand/or IgA in sera. The other clinical and serologicalfindings were unremarkable or consistent with theirhaematological condition.The histopathology was characterized by a variety offindings, all of which were consistent with an arthropodbite reaction. In particular, a wedge-shaped, superficialor superficial-deep perivascular and often also inter-stitial infiltrate was present. It was mainly composed ofeosinophils in association with lymphocytes and rarelyneutrophils. The density or the depth of the infiltratevaried from case to case, also according to the age of thelesion. An oedema of the subpapillary dermis wasalways evident. One patient presented a subepidermalvesicle. In another patient spongiosis could be seen and

Eosinophilic folliculitis occurring in a patient affected by Hodgkin lymphoma

A 25‐year‐old female had a 4‐month history of bilateral cervical lymphoadenopathies, weight loss, mild fever, and severe pruritus. A few months earlier, allergological analysis had been performed which revealed raised IgE (4.6 kU/L) against fungi antigens. A right cervical node biopsy led to histological diagnosis of nodular sclerosis‐type Hodgkin lymphoma. Clinical symptoms, bilateral cervical lymphoadenopathies, and a large mediastinal involvement (revealed by chest X‐ray and thoracic TC) were characteristic of stage IIB (bulky disease). The patient was treated with adriblastine, bleomycin, vinblastine, dacarbazine polychemotherapy (ABVD). Immediately after the administration of this cycle, she developed slightly erythematous, follicular, itchy papules and pustules, localized on her scalp ( Fig. 1 ), trunk ( Fig. 2 ), and thighs. A biopsy from the scalp was obtained under local anesthesia, after patients consent. Histopathologic findings were characterized by a superficial and deep, dense perifollicular and interstitial infiltrate composed mainly of eosinophils, accompanied by few neutrophils and lymphocytes. Eosinophilic folliculitis involved the whole follicle (inferior segment, isthmus and infundibulum), and also the sebaceous gland ( Fig. 3 ). PAS revealed the presence of some spores of Pityrosporum on the epidermis and also in the follicle. Gram stains proved negative. Eosinophilic folliculitis in an immunocompromised patient was diagnosed. Laboratory findings ascertained that the eosinophil count was in the normal range (eosinophils: 1%; white blood cell count: 10 700/mm3). The lesions healed spontaneously in about 10 days. After a second cycle of polychemotherapy (without dacarbazine, because the patient suffered repeated vascular injection injuries due to this chemotherapeutic agent), new crops of lesions in the same areas developed and in a few days faded away spontaneously. The blood clotting analysis performed just before this new cycle of ABV therapy revealed an eosinophil count of 10%, with a white blood cell count of 4500 mm3. Radiotherapy and four additional cycles of ABV polychemotherapy were made; in the meanwhile, the patient did not develop cutaneous lesions. Actually she is free from Hodgkin lymphoma and from eosinophilic folliculitis.

Normal‐looking skin in oncohaematological patients after allogenic bone marrow transplantation is not normal

Background  Graft‐versus‐host‐disease (GvHD) occurs in one‐third or even half of bone marrow transplant (BMT) patients, involving three major target organs: gut, liver and skin.

In Vivo Data

The extension and severity of vitiligo guide prognosis and help making therapeutic choices. However, in spite of attempts to standardise clinical judgment, wide variations exist both in assessment rules and interpretation of their use, making intra- and inter-observer variations unavoidable. Ultraviolet (UV)-light examination and UV photography remain useful tools for the assessment of Caucasoid patients. Non-invasive instruments that use reflectance spectroscopy provide a convenient and reproducible methodology for the study of vitiligo patients and their follow-up. Reflectance confocal microscopy provides microscopical informations in vivo about changes in achromic macules both in repig-mented areas after treatments and in clinically normal-appearing skin of vitiligo patients.

Flexural erythematous eruption following autologous peripheral blood stem cell transplantation: a study of four cases: FLEXURAL ERYTHEMATOUS ERUPTION FOLLOWING APBSCT

Autologous bone marrow transplantation and autologous peripheral blood stem cell transplantation (APBSCT) are alternative therapeutic options in the treatment of various malignancies. We describe four patients undergoing APBSCT for malignancies; they developed a cutaneous eruption characterized by confluent erythematous and hyperpigmented patches within the flexural areas during the first month after transplantation. The lesions were poorly circumscribed without epidermal changes such as scaling, xerosis, erosions or atrophy. The skin patches were treated with topical corticosteroids and resolved within a few days with discoloration. Histopathological findings were characterized by focal vacuolar degeneration of the basal layer with epidermal dysmaturation. We believe that these cutaneous eruptions are consistent with an interplay of high‐dose chemotherapy and local factors such as friction, local skin temperature and eccrine gland distribution, which could explain the constant location of this eruption in the axillae and genital area.