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Fragile skin

Struggling with the sun

Researchers, doctors and residents of a village get together to control a hereditary disorder aggravated by exposure to daylight

from Araras, Goiás

eduardo cesarPioneers in the village of Araras: from left to right, Lucas Freire from Portugal; Joaquim Freire (Lucas’s son) and Verônica Gomes; Joaquina Freire Machado and Teófilo Machado from Mãe de Deus (Joaquim’s son) with their three daughters, Darcy Machado dos Santos, Maria Verônica and Adda Maria da Mãe de Deuseduardo cesar

Djalma Jardim seems happy after a long depression that kept him from leaving his home. Today, he cheerfully talks with his friends and looks after his new ice-cream parlor with its large verandah, in the village of Araras, 260 km from Goiânia. He prefers sunny days, which bring in more people for his sweet corn, avocado or soursop ice-cream, but he knows that he himself cannot go out into the sun. Djalma has a hereditary genetic disorder known as xeroderma pigmentosum, which mainly affects those parts of the body most exposed to sunlight.

His face has been considerably transformed. An external prosthesis covers what used to be his upper lip, nose, part of his cheeks and his right eye, all of which had to be removed. At 37, Djalma has an automobile, but to protect himself from the sun for years he rode a bicycle covered from head to foot in brown paper with an opening to see where he was going.

It is ironic that in a place that is very hot at this time of year and baking in January probably the biggest concentration in the world of people who are very sensitive to the sun’s ultraviolet radiation live. Of the 1,000 or so residents of Araras, 22, aged 9 to 78, know they have xeroderma pigmentosum or XP. Some just have dry skin with blotches, while others have had to have prosthetic reconstruction on their faces and talk with difficulty. Some look after themselves, while others deny the disease, claiming that they are unable to stop working during the day in their fields. Almost everybody there makes a living from agriculture or livestock farming.

For three days at the beginning of August researchers from São Paulo and Rio de Janeiro met with biologists from the Federal University of Goiás (UFG) and from the Goiás State Department of Health, with doctors from the main hospitals in Goiânia and with residents of Araras. Together, they planned the examinations that should allow the mutation responsible for xeroderma in the residents of Araras to be identified. They also looked at what adjustments are necessary in the medical help these people are offered.

eduardo cesarMilk producer, Lázaro Silva, 71: in the region since 1963eduardo cesar

“Here in Goiás this is a public health problem,” said Carlos Menck, a geneticist from the Institute of Biomedical Sciences at the University of São Paulo (USP), in a presentation to biologists and doctors at the beginning of August at UFG. “I’d like to invite you to work on this problem. What we’ve done may help people with XP a lot.” From the audience, dermatologist Sulamita Chaibub, head of a multidisciplinary team from the Goiania General Hospital, which is currently treating 25 people with XP, said: “Send us more patients, please.”

XP is a rare disorder for which there is no specific medication. It is caused by harmful mutations in genes which, when normal, induce the production of the proteins that correct the DNA damage caused by the sun’s ultraviolet radiation or by lamps. Without these proteins, DNA accumulates damage that can give rise to tumors. People with alterations in these repair genes are a thousand times more at risk of developing skin cancer and are more susceptible to other types of cancer, eye lesions and neurological problems than people without these mutations.

Nationwide, the total number of diagnosed cases is less than 100, but preliminary estimates, based on the prevalence in other countries, indicate that 1,000 people in the country may have the disease, which is easily confused with others; at the beginning of the last century it was viewed as a form of leprosy and today may pass as an allergy to the sun or skin cancer. “As there are few records, the extent of this problem in the population is still unknown and underestimated,” says Januário Bispo Cabral Neto, a geneticist from the Federal University of Rio de Janeiro (UFRJ) who visited Araras for the first time in August.

Mozambique, a common origin
Menck believes he is on the track of the probable mutation, which seems to be different from those already known, and this year intends to start sequencing a set of genes from 18 residents of Araras in search of alterations in the 8 DNA repair genes already associated with the disorder. “Characterization of a mutation can help identify the problem early on and lead to guidance as to how the people and families should be monitored to avoid the disease becoming more serious,” says Dr .Maria Isabel Achatz, from the A.C. Camargo Cancer Hospital in São Paulo.

MAP DANIEL DAS NEVESMaria Isabel and Karina Santiago tracked the mutations responsible for the disease in two genes, XPA and XPC, in 21 people with XP in 9 states (Amazonas, Acre, Ceará, Paraíba, Sergipe, Minas Gerais, Rio de Janeiro, São Paulo and Rio Grande do Sul). They identified a new mutation in the XPC gene and another fairly frequent one, which a team of French researchers had found in 18 residents of black origin from Mayotte Island in South Africa. The coincidental results suggest that members of a same family with this mutation may have emigrated from Mozambique to the island and to Brazil; this is an intriguing conclusion, since cases of xeroderma in blacks in Brazil are fairly rare.

“At least one of the eight genes with mutations that cause XP must have come with the slaves from Mozambique,” says Menck. He and his team identified the mutation responsible for the disease in three Brazilian families, but he recognizes that “the gain for the patients in terms of treatment was unfortunately very small.” His view is that by indicating the genetic origin and possible evolution of the disorder,  the benefit for the residents of Araras may be greater. Historically, the village began forming around 1705 with the arrival of the Freire, Jardim and Gonçalves families, who bought land in the region belonging to the municipality of Faina. “Dona Clementina, a matriarch of the village, used to say that her grandfather, Augusto Gomes, had ‘bad skin’, indicating that the first cases of xeroderma may have arisen at least 150 years ago, probably through marriage between cousins,” he says. Clementina Gomes Jardim died aged 102 in 2010, without the disease that had been transmitted to some of her children and grandchildren.

In 1963 a further six families arrived from Hidrolândia, a municipality 240 km away. At 71, thin and short, with a broad smile, Lázaro Alexandre da Silva arrived that year and remembers having seen relatives with what they called skin cancer. He himself has a mild form of xeroderma, which has left him with dark blotches on both his feet, between his ankles: “It’s difficult to cure,” he says.

Apparently, Lázaro Silva is not downhearted: those who have diseases that affect the appearance normally experience discrimination, but in Araras the people with XP, even at an advanced stage, are treated naturally, working and living side by side with friends and relatives. Every day he wakes up before 6 a.m. to milk the 16 cows he currently owns, which at this dry time of the year give him 20 liters of milk. His wife, Divina Rosa da Silva, short, stout and with deep blue eyes, sometimes takes the place of her husband, gets onto the cart and takes the day’s milk to the village milk factory. She knows: “The sun isn’t good for him. When he spends a long time in the sun he gets dizzy. He’s got low blood pressure.”

Fleeing from the sun
To avoid the sun and postpone the appearance of symptoms, people with XP wear (or should wear) long clothes, preferably with a high capacity for filtering out ultraviolet radiation, baseball caps or wide-brimmed hats, dark glasses and a minimum factor 60 sun block. Menck’s team, in collaboration with a cosmetics company, compared the efficiency of 17 commercial products, with protection factors between 1.5 and 60, and concluded that generally sun blocks are efficient for protecting people from the unwanted effects of ultraviolet radiation.

eduardo cesarThe center of the village of 1,000 residents: very hot in the middle of the year and baking in Januaryeduardo cesar

Access to creams, however, is not always easy. “Many patients get here in a serious state because they have no money to buy sun block,” says Maria Isabel. “It’s essential that the supply of sun block be free from the Brazilian Public Health System (SUS) for all those who have xeroderma pigmentosum. The cost would be a lot less than treating melanoma.”

Another problem is that even for people with a lower risk of skin cancer, the creams may lose their effectiveness if the right amount is not applied, if they are not used as often as they should be, or when they do not cover all areas of the body that should be protected, warned dermatologist Fernando Stengel, President of the Argentinean Skin Cancer Foundation, at an international congress on skin cancer held in São Paulo at the beginning of August.

As simple protection measures against the sun may help delay the appearance or worsening of the disease, researchers and residents of Araras have begun to think about how to install films for filtering out ultraviolet light in the windows of the school, churches (one Catholic and the other evangelical) or in the town council’s people carrier, which takes people with XP every week to Goiânia for their routine medical check-ups. In the ice-cream parlor, they also talked about the possibility of keeping out the sun with canopies or corridors covered with plants between houses, the school and the churches.

In France, children and young people with XP (called ‘children of the moon’ because of their nocturnal habits) have the right to request the installation of anti-ultraviolet filters on the windows of schools or universities. There are specific laws that ensure medical assistance in public hospitals for those who have a Social Security card, the equivalent of the Social Welfare card in Brazil. “We managed to get Social Security to provide each child with XP with € 1,300 [R$ 3,300] per year to buy clothes, glasses, masks and anti-ultraviolet filters,” says Alain Sarasin, a geneticist from the Gustave Roussy Institute near Paris, and one of the foremost world authorities on the study of DNA repair mechanisms. On Mayotte Island, where his team identified a mutation responsible for the disease, he observed that children with XP are grouped in the same school with special teachers in air-conditioned rooms and sun protection.

“Xeroderma can be controlled, provided people have no contact with sunlight,” guarantees Maria Isabel, giving the example of a little boy who lives in São Paulo and was 4 years old when she saw him for the first time. Today, the boy, who is now 7, only has slight blotches on his face. According to Maria Isabel, he is always well covered up with clothes, baseball caps and gloves, at his mother’s insistence, and he goes to a public school whose principal agreed to block out ultraviolet radiation. “People with XP have to be looked after from early on,” Sulamita insists.

EDUARDO CÉSARResidents of Araras on Saturday night, August 11, under the light of one of the churches: Djalma Jardim is the first on the right and Gleice Machado is the fourthEDUARDO CÉSAR

Control of the disease implies medical, dental and psychological care and genetic counseling on the risk of couples having children with this disorder. “Marriage between cousins, which was fairly common in Araras, increases the risk of having children with XP,” says Menck. “When the couple has the mutation, even though they don’t have the disease, the probability of having a child with XP is 25%.” He believes in the possibility of using more efficient sun blocks, capable of correcting lesions in the DNA, or of correcting the defective genes by means of gene therapy.

“One of our problems is that everything is very slow,” observes Gleice Machado, principal of the school, owner of the village store and president of the Brazilian Xeroderma Pigmentosum Association (ABRAXP), created in 2010. “Release of the funds for the work of covering the sports’ court was signed 15 days ago by the governor, six months after it was approved.”

It was Gleice who was responsible for having the disease correctly identified, when she went with her son, Alisson, to Sulamita Chaibub’s consulting room in the Goiânia General Hospital in 2009. Two years earlier Sulamita had examined the boy with his white skin and red hair and had not detected any sign of xeroderma, but now the signs were clearer. The doctor began her diagnosis: “He has…” The mother interrupted her: “Xeroderma?!” The doctor asked if Gleice knew other people with XP, and she told her that there were many in Araras.

Relief and anguish
A series of reports by Renato Alves, published soon after in Correio Braziliense in October 2009, highlighted how the residents of Araras with XP had been neglected and mobilized the public prosecutor’s office, which demanded that hospitals in Goiânia pay more attention to these people. The news motivated pharmacist Evandro Tokarski, the owner of a pharmacy near the Goiânia General Hospital, to prepare free sun block for residents of Araras and senator Lúcia Vânia (PSDB-GO) to introduce a bill providing sickness benefit and disability pensions for people with XP.

The reports reached Menck, who for 34 years had been working in a laboratory with human cells with XP. In July 2010, when they visited Araras for the first time, he and biologist André Schuch, then on his team, measured the ultraviolet radiation in the houses, school and on the church patio. When the inhabitants of the village saw how intense the luminosity was in the village and heard Menck’s explanations, they began to see the logic of the condition that for decades had pursued their uncles, cousins and siblings and that previously had been seen as a curse, or a contagious disease, or one transmitted sexually. The reports indicate that their relief at having finally got to the bottom of the origin of the problem became confused in their anguish at not knowing how to deal with what they had and implied radical changes in their lifestyle.

“Constant struggle”
In February 2011 Gleice published the book Nas asas da esperança – A história de dor e resistência da comunidade de Araras [On the wings of hope – The history of the pain and resistance of the community of Araras], which motivated a team from the Pontifical Catholic University (PUC) of Goiás to produce the film, Sol inimigo [Enemy Sun], released on June 28 of this year at the Film Festival of Goias, a nearby city. The film has memorable and strong statements, like that of Djalma Jardim, “I’ve got the faith and will to live,” and of Avelino Gonçalves da Silva, “I’m being eaten by cancer.” Gleice says that the film has helped convince those who did not imagine how devastating the disease can be, but medical care in Goiânia is still weak: “If a hospital attendant is replaced, it begins all over again. It’s a constant struggle.”

Januário Cabral, from UFRJ, observes: “Ignorance of the problem leads to unnecessary complications for patients, parents, teachers and doctors.” In 1998 he met Ana Clara Guimarães Recchione, who had had a long battle with teachers and doctors. At the beginning of the 1990s, in Cabo Frio on the Rio de Janeiro State coast, Ana Clara saw that when her daughter, born in 1989, and son, born in 1992, went out into the sun they came back with a severe skin irritation that lasted for days. Seeing that the situation could recur, for many years she did not sleep at night and kept her children awake so they would sleep during the day and thus avoid damage by the sun. When the children had to go to school she covered them with big hats, from which cloths hung down to protect them from the sun. The teachers looked at her suspiciously when she said that her children could not go in the sun. From searching on the Internet, Ana Clara suspected that it could be xeroderma pigmentosum, but the doctors disagreed.

“It wasn’t a failing of the doctors, because no one in the family had XP, and the mother protected her children so well – there was no way she’d let them get any sun – that all they had was just a dry skin condition and it wasn’t possible to say that it was XP,” says Cabral, who came across the woman’s request for help on the Internet. Cabral and Sarasin, who was in Rio, met the mother at the university hospital, along with the doctor who attended her. They collected skin samples from the children, cultivated the cells in the laboratory, tested sensitivity to ultraviolet radiation and a month later confirmed the mother’s suspicions. In Araras, Cabral talked to Gleice and left there with recommendations, plans and bottles of sun block that she asked him to deliver to Ana Clara.

1. DNA repair genes: functional analysis and evolution (nº 2003/13255-5); Modality Thematic projects; Coordinator Carlos Frederico Martins Menck – ICB/USP; Investment R$ 1,442,484.59 (FAPESP)
2. Characterization of germinal mutations present in the XPA and XPC genes in Brazilian patients clinically diagnosed with xeroderma pigmentosum (nº 2009/16895-1); Modality Regular Research Funding; Coordinator Maria Isabel Alves de Souza Waddington Achatz – Antonio Prudente Foundation, A. C. Camargo Hospital; Investment R$ 198,003.24 (FAPESP).