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On-line version ISSN 1806-4841
An. Bras. Dermatol. vol.85 no.5 Rio de Janeiro Sept./Oct. 2010
Cutaneous manifestations of internal malignancies in a tertiary health care hospital of a developing country*
Manifestações cutâneas de doenças malignas em um hospital terciário de um país em desenvolvimento
Alex G. Ortega-LoayzaI; Willy RamosII; Ericson L. GutierrezIII; Patricia Chavez de PazIV; Lucia BobbioV; Carlos GalarzaVI
IMD; Medical Resident. Department of Dermatology. Virginia Commonwealth University - Richmond, VA, USA
IIMD; Institute of Clinical Investigation, National University of San Marcos (UNMSM) - Lima, Peru
IIIMD; Institute of Clinical Investigation, National University of San Marcos (UNMSM) - Lima, Peru
IVMD - Dermatologist, Dermatology Service, Dos de Mayo National Hospital - Lima, Peru
VMD - Dermatologist, Dermatology Service, Dos de Mayo National Hospital, Lima, Peru
VIMD; Institute of Clinical Investigation, National University of San Marcos (UNMSM) - Lima, Peru
In a public hospital in Lima, Peru, 24 patients with 16 types of paraneoplastic dermatoses were identified by data collection. The most frequent dermatosis was dermatomyositis (four patients). The other dermatoses were malignant acanthosis nigricans, palmoplantar keratoderma, bullous dermatoses, lymphomatoid papulosis, edematous scarring vasculitic panniculitis, Norwegian scabies, primary systemic amyloidosis, necrolytic migratory erythema, infective dermatitis, pancreatic panniculitis, generalized pruritus, Lesser-Trelat syndrome, and acquired ichthyosis. Most of these paraneoplastic dermatoses were diagnosed before (45.8%) or at the time of (38.5%) the diagnosis of the underlying malignancy. The most frequent underlying malignancies were lymphoma, adenocarcinomas of the upper digestive tract, and malignant neoplasms of the pancreas. The average age of the patients was 47.0 ± 16.9 years and the length of the disease since diagnosis was 13.7 months. The mortality rate was 75%. Paraneoplastic dermatoses are rare dermatologic entities that are difficult to diagnose. Surveillance is also hampered when patients do not have easy access to health care centers due to financial and geographical issues. However, when identified, they might facilitate the early diagnosis of an associated tumor and contribute to increase the surveillance of patients.
Keywords: Dermatomyositis; Lymphoma; Paraneoplastic syndromes
Em um hospital público em Lima, Peru, 24 pacientes com 16 tipos de dermatoses paraneoplásicas foram identificados por meio de coleta de dados. A dermatose mais frequente foi dermatomiosite (quatro pacientes). As outras dermatoses foram acantose maligna, queratodermia palmoplantar, dermatoses bolhosas, papulose linfomatóide, cicatriz edematosa, paniculite e vasculite, escabiose norueguesa, amiloidose sistêmica primária, eritema necrolítico migratório, dermatite infecciosa, paniculite pancreática, prurido generalizado, sinal de Leser-Trelat e ictiose adquirida. Grande parte dessas dermatoses foi diagnosticada antes (45,8%) ou no momento (38,5%) do diagnóstico do tumor subjacente. Os tumores malignos mais frequentes foram linfoma, adenocarcinomas do trato digestivo superior e neoplasias malignas do pâncreas. A idade média dos pacientes foi de 47.0 ± 16.9 anos e a duração da doença desde o diagnóstico foi de 13,7 meses. A taxa de mortalidade foi de 75%. Dermatoses paraneoplásicas são condições dermatológicas raras de difícil diagnóstico. O controle também é prejudicado quando pacientes não têm acesso fácil à centros de saúde por questões financeiras ou geográficas. No entanto, quando identificadas, elas podem facilitar o diagnóstico precoce de um tumor associado e contribuir para um aumento do controle dos pacientes.
Palavras-chave: Dermatomiosite; Linfoma; Síndromes paraneoplásicas
Paraneoplastic dermatoses are ailments that arise in association with a malignancy elsewhere in the body. These dermatoses represent a heterogeneous group of clinical manifestations which might appear in association with a malignancy. They are the second most common paraneoplastic disease after the endocrinologic paraneoplastic syndromes. 1,2 Paraneoplastic dermatoses are characterized by a diverse range of cutaneous changes, some of which appear benign. Therefore, they may go unnoticed by the physician.1
The criteria for a certain set of skin diseases to be considered paraneoplastic dermatoses are shown in table 1. In fact, the first two criteria (major criteria) are sufficient to consider a dermatosis as paraneoplastic.1-4
The frequency with which some benign dermatoses are associated with underlying malignancy suggests that this is not random; however in most cases it is difficult to demonstrate a cause-effect relationship with the primary tumor. The current literature suggests that these phenomena are the result of the interaction between the tumor, some mediator factors and the involved tissue.3,4
The mediators are generally polypeptides, hormones, cytokines, antibodies and growth factors. These mediator factors interfere with cell to cell communication, resulting in an increase of cellular activity. 3,4 In a previous review, more than 40 dermatoses were found to be reported as paraneoplastic. 3 The paraneoplastic dermatoses might be categorized in three different groups (Table 2).
In this study, we reported 24 cases of paraneoplastic dermatoses as well as the underlying malignancies in a tertiary health care hospital of a developing country.
In the Dos de Mayo National Hospital, Lima, Peru, between July 1993 and June 2007, we found 24 patients with 16 types of paraneoplastic dermatoses using data collection (Figure 1-6). The incidence of paraneoplastic dermatoses was approximately 4.5% every year. 66.7 % were male and 33.3 % female. The average age of the patients was 47.0 ± 16.9 years-old, 20 (74.9%) patients were between 30 and 69 years old.
At the time, the average duration of illness at the diagnosis of malignancy was 13.7 months with a fatal outcome in 18 patients (75.0 %). In 45.8 % patients, the diagnosis of paraneoplastic dermatoses was made before the diagnosis of cancer; in 38.5 % of patients the diagnosis was made simultaneously and in the rest the diagnosis of paraneoplastic dermatosis was made after the diagnosis of the neoplasia.
When a dermatosis was diagnosed before the neoplasia, the diagnosis was made 7.5 ± 4.2 months before (range 3-18 months) (Table 3). On the other hand, when a dermatosis was diagnosed after the neoplasia the diagnosis was made 6.8 ± 1.0 months after (range 6-8 months) (Table 3).
Four patients, who had the diagnosis of infective dermatitis, Norwegian scabies acquired ichthyosis and tripe palms, showed reactive serology for HTLV-I (Human T-Lymphotropic virus) by ELISA (Enzyme Lynked immunosorbent Assay).
The most frequent dermatoses were dermatomyositis and immuno-bullous dermatoses. The most frequent underlying malignancies were lymphoma, upper digestive tract adenocarcinomas and malignant neoplasm of pancreas.
In eight patients, the average time between diagnosis and remission of the malignancy after treatment was between 15 days and 12 months after the time of diagnosis of the dermatoses. In the other ones, the dermatoses remain unchanged.
The clinical characteristics of paraneoplastic dermatoses in our country seem to be similar to those in developed countries; 2-4,9,10 however, our patient population delayed seeking medical attention resulting in a high mortality rate. Also, the mean age of patients (47 years) was relatively low; however this could be explained by the presence of patients between 17 and 24 years old. Histopathologic tests are the most important diagnostic tool to confirm the diagnosis of paraeoplastic dermatoses. They provide physicians enough credible information to look for a subjacent malingancy. In general, the histopathologic findings of the paraneoplastic dermatoses described in this study were similar to those reported worldwide. 1-4
In our study, the most frequent neoplasm associated with paraneoplastic dermatoses was NonHodgkin's lymphoma. The dermatoses associated with this type of lymphoma were paraneoplastic immunobullous dermatoses, lymphomatoid papulosis, edematous scarring vasculitic panniculitis, norwegian scabies, infective dermatitis, generalized pruritus and acquired ichthyosis. It was previously described the association of lymphoproliferative neoplasm with acanthosis nigricans, Lesser-Trelat syndrome, paraneoplastic vasculitis and pityriasis liquenoides. 5 Other authors have noted additional non-infectious dermatoses associations such as acquired ichthyosis, 1, 3, 4, 6 immuno-bullous dermatosis, erythema annular centrifugum, pruritus, Sweet's syndrome, 3,4 scleromyxedema, 3 systemic amyloidosis, 1 and infectious dermatitis such as norwegian scabies and infective dermatitis. 7
In our study, the most frequent solid tumor was adenocarcima of the upper digestive tract (esophagous and stomach), malignant neoplasm of pancreas and with less frequency neoplasms of the lung, breast, ovary and prostate. Dermatomyositis was the most frequent dermatosis. This disease has an unknown etiology, and it is characterized by the pres-ence of inflammatory myopathy and typical cutaneous lesions. Dermatomyositis is associated with malignant neoplasia in between 6 and 60% of the cases, such as breast cancer (4-11%), nasopharyngeal cancer (0-58%) and ovarian cancer (2-12%). 8-10
Our results are similar to those reported previously, where the paraneoplastic dermatoses associated with solid tumors were muscoloskeletal disorders (including dermatomyositis), reactive erythemas, vascular dermatoses, papulosquamous disorders (acanthosis nigricans, tylosis, acquired ichthyosis) and growth of hair.10
Also, all our patients had a significant weight loss following the diagnosis of cancer. The course of the disease was fatal in most of them. 11 Three (11.5%) of our cases initiated with immuno-bullous disorders, but the rapid course and negative response to systemic corticosteroids were enough evidence to suspect the presence of malignancy, which were associated with lymphomas in two of them.
Four patients had ELISA positive serology for HTLV-I. These patients presented with infective dermatitis, norwegian scabies, acquired ichthyosis and tripe palms, which progressed to T-cell adult lymphoma.12
In general, only case reports and review articles have described the characteristics of paraneoplastic dermatoses. 13, 14, 15 The paraneoplastic dermatoses seen in the patient population in a public hospital in Lima between 1993 and 2007 are rare entities with difficult clinical recognition and diagnoses. The early diagnosis might initiate the diagnosis of patients with an underlying malignancy. The surveillance is also hampered when patients do not have easy access to health care centers due to financial and geographical issues. For this reason, the early recognition of these cutaneous signs of internal malignancy is important not only for dermatologists but also for general practitioners, who have the opportunity to see patients first or are the only type of doctors in underserved areas.
In conclusion, the most common paraneoplastic dermatosis was dermatomyositis and the most frequent underlying malignancy was lymphoma. In our developing country, although most of the dermatoses were diagnosed before or concomitantly with the underlying neoplasia, the mortality rate remained high.
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Alex G Ortega-Loayza
Department of Internal Medicine Virginia Commonwealth University
PO Box 980509
Richmond, VA 23298 0509
Tel./Fax: 919 619 4096 / 804 828 4926
Approved by the Advisory Board and accepted for publication on 27.11.09.
Conflict of interest: None / Conflito de interesse: Nenhum
Financial funding: None / Suporte financeiro: Nenhum
* Work conducted at the Virginia Commonwealth University, Richmond - Virginia, USA.