Pulmonary hypertension in Gaucher's disease by pyb17727



The current annual cost of the six basic            randomised trial of immunogenicity of      received 30 U/kg per month. The lung,
vaccines in the Dominican Republic                  fractional-dose and two-dose regimens.     like the brain, and perhaps bone, may
                                                    Lancet 1998; 351: 1472–76.
are: US$95460 for diphtheria-                   2   Booy R. Getting Hib vaccine to those who   represent sequestered sites not readily
pertussis-tetanus (DPT); $141 140 for               need it. Lancet 1998; 351: 1446–47.        accessible to circulating enzyme. In
oral poliomyelitis vaccine; $226270 for                                                        this scenario, a low-dose regimen may
measles; $46 640 for BCG; 51660 for                                                            not be sufficient to overcome a
tetanus toxin; and $97020 for                                                                  threshold and allow an adequate
diphtheria-tetanus. The subtotal for            Pulmonary hypertension in                      enzyme concentration at the site of
all basic vaccines is $658190. The                                                             pathology, especially if there are
addition of hepatitis B vaccine                 Gaucher’s disease                              fibrotic or necrotic regions. Although
($590400), which is currently part of           Sir—Deborah Elstein and co-workers             not reported for Gaucher’s disease,
the Dominican EPI programme,                    (May 23, p 1544) 1 report a 7%                 due to the absence of a long-term
nearly doubled the total cost of                incidence of pulmonary hypertension            surviving       animal   model,     the
vaccines.                                       in patients with type 1 Gaucher’s              observations in other models of storage
    The projected cost of the Hib               disease. Although we have not                  diseases show a tissue dose-response
vaccine is $2 880 000, more than twice          undertaken echocardiography and                gradient.3,4
as much as the entire EPI, including            pulmonary function tests on all our               Enzyme therapy is expensive.
hepatitis B. Even with fractional doses,        patients with Gaucher’s diease, our            However, patients with symptomatic
the cost of the vaccine would be high,          experience is different from that              Gaucher’s disease on enzyme-
but could be within reach for some              reported by Elstein. We have followed          replacement therapy have shown
countries that currently cannot afford          180 patients on enzyme-replacement             significant improvements in health-
it.                                             therapy.                                       related quality of life. 5 Although
    Booy states that fractional doses are          Of 150 patients, baseline pulmonary         lysosomal accumulation of under-
impractical unless the vaccine is               hypertension was recorded in only              graded substrate may represent the
reformulated. He notes that using a             three patients (splenectomised, with           initiating insult, other mechanisms
single vial several times raises issues         severe systemic disease and interstitial       may promote the various clinical
of preservative and infectious                  lung disease). We have not found any           expressions of Gaucher’s disease.
contamination. However, DPT, BCG,               indicaton of progressive pulmonary             Treatment may alter the natural
measles, and hepatitis B are all used in        disease in these patients. Five patients
multidose vials that involve placing a                                                         history      of   the  disease,    with
                                                with interstitial lung disease and three       unpredictable long-term outcomes and
needle in the vial as many as ten times.        with pulmonary hypertension had
Preservative is not a problem if both                                                          even adverse effects, which underlines
                                                substantial haematological and hepatic
doses are used immediately. Booy also                                                          the need for careful monitoring. We
                                                responses on enzyme-replacement
notes that field conditions are not as                                                         strongly disagree with the recom-
                                                therapy. Two patients died from
ideal as trial conditions, which is true,                                                      mendation to withdraw treatment in
                                                unrelated causes. Necropsy showed
but is not a reason not to try fractional                                                      symptomatic patients, because it
                                                histological changes indicative of a
doses. If the results in Chile can be           response to therapy—ie, minimum                would increase the risk of disease
replicated, trying fractional doses in a        accumulations of Gaucher cells were            progression without definitive evidence
widespread programme will show how              seen in the lung interstitium, along           of the relation between treatment and
effective it is.                                with many normal macrophages,                  pulmonary hypertension.
    More and more vaccines will                 which contrasts with the findings from
become available with time. Market              an open-lung biopsy performed before           *Gregory M Pastores, Albert Miller
competition will eventually bring the           enzyme-replacement therapy.                    Neurology, Pediatrics, and Human Genetics,
prices down, but as we have seen with              Since we did not screen all the             New York University School of Medicine,
                                                                                               New York, NY 10018, USA; and Community
Hib, this process can take more than            patients, there may be some with               Medicine Mount Sinai School of Medicine,
10 years. As an alternative, Booy               subclinical increase in pulmonary              New York
suggests that the way for vaccines to           pressures, but, if this is true, none of
reach developing countries is for               the patients showed any signs of               1   Elstein D, Klustein MW, Lahad A, et al.
industrialised countries to supply or           progression to the point of developing             Echocardiographic assessment of
                                                                                                   pulmonary hypertension in Gaucher’s
subsidise vaccines. This approach has           symptoms. Our patients may differ                  disease. Lancet 1998; 351: 1544–46.
not happened with Hib vaccine, and              from those in Elstein’s study, perhaps         2   Pastores GM, Sibille AR, Grabowski GA.
would make developing countries                 in their concurrent or inter-current               Enzyme replacement therapy in Gaucher
dependent on the generosity of                  medical disorders. Interpretation of               disease type 1: dosage efficacy and adverse
industrialised countries. From the              the data reported by Elstein and                   effects in 33 patients treated for 6 to 24
                                                                                                   months. Blood 1993; 82: 408–16.
perspective of the Dominican                    colleagues is complicated since only
                                                                                               3   Kikuchi T, Yang HW, Pennybacker M,
Republic and other developing                   limited information on patients is                 et al. Clinical and metabolic correction of
countries who do not want to wait               provided. The patients in their study              Pompe disease by enzyme therapy in acid
longer, fractional doses may offer an           may have comorbidities that might                  maltase-deficient quail. J Clin Invest 1998;
opportunity to provide protection to            predispose them to pulmonary                       101: 827–33.
their children.                                 hypertension, which tends to occur             4   Sands MS, Vogler C, Torrey A, et al.
                                                                                                   Murine mucopolysaccharidosis type VII:
                                                with severe extrapulmonary mani-
                                                                                                   long-term therapeutic effects of enzyme
*Jesús M Feris, Z acarías Garib                 festations in patients with Gaucher’s              replacement and enzyme replacement
*Infectious Diseases Department, Hospital       disease.                                           followed by bone marrow
Infantil Dr Robert Reid Cabral, Santo              Our therapeutic outcomes may be                 transplantation.
Domingo, Dominican Republic; and Natiional      different from those of Elstein because            J Clin Invest 1998; 99: 1596–605.
Immunization Programme, Santo Domingo.                                                         5   Damiano AM, Pastores GM, Ware JE. The
                                                of the treatment regimens. Our
                                                                                                   health-related quality of life in adults with
1   Lagos R, Valenzuela MT, Levine OS, et al.
                                                patients received higher doses of                  Gaucher disease receiving enzyme
    Economisation of vaccination against        enzyme (100–120 U/kg per month),2                  replacement: results from a retrospective
    Haemophilus influenzae type b: a            whereas most of Elstein’s patients                 study. Qual Life Res 1998; 7: 373–86.

580                                                                                                THE LANCET • Vol 352 • August 15, 1998

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