High incidence of pulmonary arterial hypertension in systemic sclerosis patients with anti-centriole autoantibodies

Abstract

Systemic sclerosis (SSc)-related autoantibodies are useful tools in identifying clinically homogenous subsets of patients and predicting their prognosis. In this report, we described five SSc patients with anti-centriole antibodies. All five patients were females and had digital ulcers/gangrene. Four of five (80%) patients had pulmonary arterial hypertension (PAH). None of the five patients had active pulmonary fibrosis or developed renal crisis. Anti-centriole antibodies may be a marker for PAH and digital ulcers/gangrene.     

Novel light treatment for digital ulcers in systemic sclerosis: a feasibility study

Background

Locally acting, well-tolerated treatments for digital ulcers in patients with systemic sclerosis are needed. We aimed to investigate the safety, feasibility, and tolerability of a novel light treatment, and to tentatively assess treatment efficacy.

Juvenile onset systemic sclerosis: a single center experience of 23 cases from Asia

The aim of this paper was to study the spectrum of juvenile scleroderma (JSSc) seen at a tertiary care referral center in Asia. Retrospective analysis of case records of patients with systemic sclerosis, having age of onset less than 16 years and seen at our hospital from 1988 to 2004, was done. Patients with linear scleroderma and morphea were excluded. There were 23 patients (19 girls, 4 boys) with median age of onset of 12 years (range 5–16 years). The median age at presentation was 17 years (range 10–34 years). The median time from first symptoms to presentation was 4 years (range 0.2–26 years). Among these, 14 had diffuse systemic sclerosis (DSSc), while 9 had limited scleroderma (LSSc). The clinical features seen at presentation in patients were: Raynaud’s phenomenon in 19, digital ulcers in 14, loss of finger tip pulp in 12, reflux in 8, dysphagia in 7, arthritis in 8, digital gangrene in 2, and pulmonary artery hypertension in 1. Antinuclear antibody was positive in 15 out of 18 patients tested. Interstitial lung disease was seen in 15 patients, 6 of whom had diffuse disease. The median skin score was 22 (range 7–48) .One patient died of primary pulmonary hypertension within 1 year of onset of symptoms. At a mean follow-up of 34 months, 14 patients were stable or had improvement in skin score or dyspnea on exertion. DSSc and LSSc in childhood have a clinical presentation similar to adult patients, with cardiopulmonary involvement being the major predictor of outcome. The short-term prognosis of JSSc is good.     

Circulating lupus type anticoagulant and pulmonary hypertension associated with mixed connective tissue disease

Summary We report the case of a young woman, with mixed connective tissue disease (MCTD), associated with disabling pulmonary hypertension and presence of the lupus anticoagulant. The lupus anticoagulant, an antibody directed against phospholipid components, was linked in our patient to extensive thrombophlebitis and premature labor. Raynaud's phenomenon progressed towards finger necrosis in spite of optimal vasodilating treatment. The part played by the lupus anticoagulant in pulmonary hypertension remains to be established. Both these complications responded to prednisolone therapy, but the improvement was limited and short-lived.     

Survey of Raynaud's phenomenon and systemic sclerosis based on a representative study of 10,000 south-Transdanubian Hungarian inhabitants

OBJECTIVES: To assess the prevalence of Raynaud's phenomenon (RP) and of RP associated systemic sclerosis (SSc) in a large regional representative study. METHODS: Ten thousand individuals aged between 14-65 years participated in face-to-face interviews. The stratified sample of the South-West Hungarian population was representative for age, sex and urban or rural residence. Individuals reporting complaints suggesting the presence of "clinically significant" RP were asked to undergo a clinical investigation. Patients showing complaints provoked by taking something out of the freezer (-20 degrees C) compartment of the refrigerator and/or whether they had experienced digital ulcers were sorted into this category. RESULTS: The overall prevalence of RP was at least 578.9/10,000, and the prevalence of "clinically significant" RP could be calculated as at least 87.7/10,000 inhabitants. In this latter group 17.2% of the cases had either established SSc or anticentromere antibody or scleroderma capillary pattern on nailfold capillaroscopy. SSc with "clinically significant" RP and/or ulcers was identified in a prevalence of 9.1/10.000 individuals, whilst there was a prevalence of 14.7/10,000 of RP with either anticentromere antibody or scleroderma capillary pattern. CONCLUSIONS: "Clinically significant" RP affects almost 1% of the population. We identified cases with early stages of scleroderma spectrum disorder showing either anticentromere autoantibody or scleroderma capillary pattern. The prevalence of SSc was found to be higher than expected. It is reasonable to screen "clinically significant" RP cases for scleroderma-related symptoms because this approach makes it possible to identify patients with both SSc and early scleroderma related symptoms.     

Hemoglobin sickle cell disease complications: a clinical study of 179 cases

Background

Hemoglobin sickle cell disease is one of the most frequent hemoglobinopathies. Surprisingly, few studies have been dedicated to this disease, currently considered to be a mild variant of homozygous sickle cell disease. The aim of this study was to update our knowledge about hemoglobin sickle cell disease.

Design and Methods

The study involved a single center series of 179 patients. Clinical and biological data were collected with special attention to the assessment of pulmonary arterial hypertension and nephropathy.

Results

Hemoglobin sickle cell diagnosis was delayed and performed in adulthood in 29% of cases. Prevalence of hospitalized painful vasoocclusive crisis, acute chest syndrome and priapism was 36%, 20% and 20%, respectively. The most common chronic organ complications were retinopathy and sensorineural otological disorders in 70% and 29% of cases. Indeed, prevalence of complications reported in homozygous sickle cell disease, such as nephropathy, suspicion of pulmonary hypertension, strokes and leg ulcers was rather low (13%, 4% and 1%, respectively). Phlebotomy performed in 36% of this population (baseline hemoglobin 11.5 g/dL) prevented recurrence of acute events in 71% of cases.

Conclusions

Our data suggest that hemoglobin sickle cell disease should not be considered as a mild form of sickle cell anemia but as a separate disease with a special emphasis on viscosity-associated otological and ophthalmological disorders, and with a low prevalence of vasculopathy (strokes, pulmonary hypertension, ulcers and nephropathy). Phlebotomy was useful in reducing acute events and a wider use of this procedure should be further investigated.     

Prevention of vascular damage in scleroderma and autoimmune Raynaud's phenomenon: A multicenter,randomized, double‐blind,placebo‐controlled trial of the angiotensin‐converting enzyme inhibitor quinapril

Objective

To evaluate the efficacy and tolerability of prolonged administration of quinapril, a long‐acting angiotensin‐converting enzyme inhibitor, in the management of the peripheral vascular manifestations of limited cutaneous systemic sclerosis (lcSSc) and in the prevention of the progression of visceral organ involvement in the disease.

Methods

This was a multicenter, randomized, double‐blind, placebo‐controlled study evaluating quinapril 80 mg/day, or the maximum tolerated dosage, in 210 patients with lcSSc or with Raynaud's phenomenon (RP) and the presence of SSc‐specific antinuclear antibodies. Treatment was for 2–3 years. The primary outcome measure was the number of new ischemic ulcers appearing on the hands; secondary measures were the frequency and severity of RP attacks, skin score, treatments for ischemia, health status (measured by the Short Form 36 instrument), measures of kidney and lung function, and echocardiographic estimates of pulmonary artery pressure. An intent‐to‐treat analysis was used.

Results

Quinapril did not affect the occurrence of digital ulcers or the frequency or severity of RP episodes. It did not alter the treatments that were prescribed for either infected ulcers or severe RP symptoms. There was no apparent effect on the estimated tricuspid gradient. Health status was not affected by quinapril, and one‐half of the patients who believed they had benefited from the trial treatment were in the placebo arm. Quinapril was not tolerated by one‐fifth of the patients, with dry cough being the most frequent side effect.

Conclusion

Administration of quinapril for up to 3 years had no demonstrable effects on the occurrence of upper limb digital ulcers or on other vascular manifestations of lcSSc in this patient population.

     

Quantifying Digital Ulcers in Systemic Sclerosis: Reliability of Computer‐Assisted Planimetry in Measuring Lesion Size

Objective

Digital ulcers are a major problem in patients with systemic sclerosis (SSc), causing severe pain and impairment of hand function. In addition, digital ulcers heal slowly and sometimes become infected, which can lead to gangrene and necessitate amputation if appropriate intervention is not taken. A reliable, objective method for assessing digital ulcer healing or progression is needed in both the clinical and research arenas. This study was undertaken to compare 2 computer‐assisted planimetry methods of measurement of digital ulcer area on photographs (ellipse and freehand regions of interest [ROIs]), and to assess the reliability of photographic calibration and the 2 methods of area measurement.

Methods

Photographs were taken of 107 digital ulcers in 36 patients with SSc spectrum disease. Three raters assessed the photographs. Custom software allowed raters to calibrate photograph dimensions and draw ellipse or freehand ROIs. The shapes and dimensions of the ROIs were saved for further analysis.

Results

Calibration (by a single rater performing 5 repeats per image) produced an intraclass correlation coefficient (intrarater reliability) of 0.99. The mean ± SD areas of digital ulcers assessed using ellipse and freehand ROIs were 18.7 ± 20.2 mm² and 17.6 ± 19.3 mm², respectively. Intrarater and interrater reliability of the ellipse ROI were 0.97 and 0.77, respectively. For the freehand ROI, the intrarater and interrater reliability were 0.98 and 0.76, respectively.

Conclusion

Our findings indicate that computer‐assisted planimetry methods applied to SSc‐related digital ulcers can be extremely reliable. Further work is needed to move toward applying these methods as outcome measures for clinical trials and in clinical settings.

     

Arthritis and osteonecrosis in a patient with thrombophilia

This case report describes a very rare entity of thrombophilia manifesting as persistent arthritis and digital ulcers. A 9-year-old Egyptian girl presented with a 2-year history of persistent arthritis and digital ulcers. The case was followed up after 4 years. The clinical manifestations and laboratory investigations are recorded. Thrombophilia with partial protein C deficiency appeared to be responsible for the clinical manifestations with underlying ipsilateral osteonecrosis of patella and calcaneum and resorption of the terminal phalanges. Her older sister showed the same picture with additional pulmonary hypertension. In conclusion, arthritis and osteonecrosis appear as a rare presentation of thrombophilia and protein C deficiency, and ignorance of this may lead to misdiagnosis or confusion with other childhood rheumatic diseases.     

Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial

BACKGROUND: Pulmonary hypertension is a progressive and often fatal complication of the scleroderma spectrum of disease for which no treatment has been proven effective in a randomized trial. OBJECTIVE: To determine the effect of epoprostenol on pulmonary hypertension secondary to the scleroderma spectrum of disease. DESIGN: Randomized, open-label, controlled trial. SETTING: 17 pulmonary hypertension referral centers. PATIENTS: 111 patients with moderate to severe pulmonary hypertension. INTERVENTION: Epoprostenol plus conventional therapy or conventional therapy alone. MEASUREMENTS: The primary outcome measure was exercise capacity. Other measures were cardiopulmonary hemodynamics, signs and symptoms of pulmonary hypertension and scleroderma, and survival. RESULTS: Exercise capacity improved with epoprostenol (median distance walked in 6 minutes, 316 m at 12 weeks compared with 270 m at baseline) but decreased with conventional therapy (192 m at 12 weeks compared with 240 m at baseline). The difference between treatment groups in the median distance walked at week 12 was 108 m (95% CI, 55.2 m to 180.0 m) (P < 0.001). Hemodynamics improved at 12 weeks with epoprostenol. The changes in mean pulmonary artery pressure for the epoprostenol and conventional therapy groups were -5.0 and 0.9 mm Hg, respectively (difference, -6.0 mm Hg [CI, -9.0 to -3.0 mm Hg), and the mean changes in pulmonary vascular resistance were -4.6 and 0.9 mm Hg/L per minute, respectively (difference, -5.5 mm Hg/L per minute [CI, -7.3 to -3.7 mm Hg/L per minute). Twenty-one patients treated with epoprostenol and no patients receiving conventional therapy showed improved New York Heart Association functional class. Borg Dyspnea Scores and Dyspnea-Fatigue Ratings improved in the epoprostenol group. Trends toward greater improvement in severity of the Raynaud phenomenon and fewer new digital ulcers were seen in the epoprostenol group. Four patients in the epoprostenol group and five in the conventional therapy group died (P value not significant). Side effects of epoprostenol therapy included jaw pain, nausea, and anorexia. Adverse events related to the epoprostenol delivery system included sepsis, cellulitis, hemorrhage, and pneumothorax (4% incidence for each condition). CONCLUSIONS: Continuous epoprostenol therapy improves exercise capacity and cardiopulmonary hemodynamics in patients with pulmonary hypertension due to the scleroderma spectrum of disease.     

Clinical and laboratory features of scleroderma patients with pulmonary hypertension

OBJECTIVE: Pulmonary hypertension (PH) is a frequent cause of death in patients with systemic sclerosis (SSc). In this study, we examined the occurrence of PH and investigated the clinical and laboratory features of SSc patients with PH. METHODS: A cross-sectional study of 125 Japanese patients with SSc was conducted using Doppler echocardiography, other multiple cardiopulmonary tests, and laboratory examination. RESULTS: PH (systolic pressure >40 mmHg) was diagnosed in 20 patients (16%) by Doppler echocardiography. In the six patients who had secondary pulmonary hypertension (SPH), PH was due to severe pulmonary fibrosis; 14 patients had isolated pulmonary hypertension (IPH). An elevated erythrocyte sedimentation rate (ESR) and increased immunoglobulin G (IgG) were found in a significantly greater proportion of the patients with PH than in those without PH. The incidence of pitting scars/ulcers was significantly greater in the patients with SPH than in those without PH. CONCLUSION: Elevated ESR and increased IgG were common features of scleroderma patients with PH, and scleroderma patients with SPH were inclined to have pitting scars/ulcers.     

An autopsied case of systemic lupus erythematosus with pulmonary hypertension--a case report

The authors report an autopsied case of systemic lupus erythematosus (SLE) with pulmonary hypertension. The patient was a forty-five-year-old female who had been troubled by obstinate Raynaud's phenomenon for ten years before the definite diagnosis of pulmonary hypertension was made. Microscopic examination of the pulmonary vasculature yielded findings consistent with plexogenic pulmonary arteriopathy. However, the deposition of immune complexes in the pulmonary vascular endothelium was not detected by enzyme antibody study. This case suggests, therefore, that "pulmonary Raynaud's phenomenon" is a possible pathogenesis of pulmonary hypertension in patients with SLE.     

Clinical efficacy of sildenafil in patients with pulmonary hypertension in functional class II or III

Objective

To assess the efficacy of treatment with sildenafil monotherapy in patients with pulmonary hypertension.

Patients and methods

An observational study was undertaken in 11 patients with pulmonary hypertension in functional class II or III who received treatment with sildenafil (150 mg/day). Seven of the patients had inoperable chronic thromboembolic pulmonary hypertension and 4 had pulmonary arterial hypertension. To assess treatment response, the following parameters were assessed during follow-up at 3, 6, and 12 months: exercise tolerance in the 6-minute walk test, change in functional class, and systolic pulmonary arterial pressure measured by echocardiography.

Results

We observed a significant improvement in exercise tolerance, as shown by increased 6-minute walk distance after 3, 6, and 12 months of treatment (increases of 20, 67, and 95 m, respectively). All patients showed an improvement in functional class. The results of echocardiography did not reveal statistically significant differences in systolic pulmonary arterial pressure between baseline and 6 or 12 months of treatment. No significant adverse effects were observed, although sildenafil treatment was suspended in 1 patient due to persistent headache.

Conclusions

the results of this study confirm that sildenafil is an effective drug for the management of pulmonary arterial hypertension and inoperable chronic thromboembolic pulmonary hypertension both in the short term and medium to long term, and that the drug is well tolerated and shows few side effects.     

Brief Report: Effect of ambrisentan treatment on exercise‐induced pulmonary hypertension in systemic sclerosis: A prospective single‐center,open‐label pilot study

Objective

Exercise‐induced pulmonary hypertension (ePH) may represent an early, clinically relevant phase in the spectrum of pulmonary vascular disease. The purpose of this pilot study was to describe the changes in hemodynamics and exercise capacity in patients with systemic sclerosis (SSc) spectrum–associated ePH treated with open‐label daily ambrisentan.

Methods

Patients were treated with ambrisentan, 5 mg or 10 mg once daily, for 24 weeks. At baseline and 24 weeks, patients with SSc spectrum disorders exercised in a supine position, on a lower extremity cycle ergometer. All patients had normal hemodynamics at rest. We defined baseline ePH as a mean pulmonary artery pressure of >30 mm Hg with maximum exercise and a transpulmonary gradient (TPG) of >15 mm Hg. The primary end point was change in pulmonary vascular resistance (PVR) with exercise. Secondary end points included an improvement from baseline in 6‐minute walking distance, health‐related quality of life assessments, and cardiopulmonary hemodynamics.

Results

Of the 12 enrolled patients, 11 completed the study. At 24 weeks there were improvements in mean exercise PVR (85.8 dynes × second/cm⁵; P = 0.003) and mean distance covered during 6‐minute walk (44.5 meters; P = 0.0007). Improvements were also observed in mean exercise cardiac output (1.4 liters/minute; P = 0.006), mean pulmonary artery pressure (−4.1 mm Hg; P = 0.02), and total pulmonary resistance (−93.0 dynes × seconds/cm⁵; P = 0.0008). Three patients developed resting pulmonary arterial hypertension during the 24 weeks.

Conclusion

Exercise hemodynamics and exercise capacity in patients with SSc spectrum–associated ePH improved over 24 weeks with exposure to ambrisentan. Placebo‐controlled studies are needed to confirm whether this is a drug‐related effect and to determine optimal therapeutic regimens for patients with ePH.

     

Culture-negative subacute bacterial endocarditis masquerades as granulomatosis with polyangiitis (Wegener’s granulomatosis) involving both the kidney and lung

Background

Subacute bacterial endocarditis (SBE) occasionally exhibits positive cytoplasmic anti-neutrophil cytoplasmic antibody (c-ANCA) of the anti-proteinase-3 (PR-3) type. Clinically, it mimics ANCA-associated vasculitis, such as Wegener's disease with glomerulonephritis. Lung abscesses are the most common manifestation of lung involvement. We herein report a case of culture-negative SBE strongly c-ANCA/PR3-positive accompanied by pulmonary involvement and glomerulonephritis. In this case, we took biopsies of both the lung and kidney, although renal biopsy is usually preferred over lung biopsy. The lung biopsy showed severe alveolar capillaritis, suggesting vasculitis consistent with polyangiitis. The renal biopsy revealed glomerulonephritis with a membranoproliferative pattern. To our knowledge, this is the first such reported case.

Case presentation

A 68-year-old Chinese male patient presented to our hospital with a fever, cough, chest pain, and recurrent peripheral edema. He had a past medical history significant for treated schistosomiasis 20 years previously. Physical examination revealed palpable purpura, mild hypertension, hepatosplenomegaly, and a holosystolic cardiac murmur (Levine 2/6). Echocardiography showed tricuspid valve vegetations with moderate to severe regurgitation. Serum c-ANCA/PR3 and cryoglobulin were strongly positive. Renal biopsy results indicated membranoproliferative glomerulonephritis with several crescents. Chest CT revealed multiple intraparenchymal and subpleural nodules, and lung biopsy showed polyangiitis. The patient’s ANCA titers, glomerulonephritis, and pulmonary injury all resolved after antibiotic therapy.

Conclusion

SBE may present with positive c-ANCA/PR3, multiple pulmonary nodules, pulmonary polyangiitis, and glomerulonephritis clinically mimicking granulomatosis with polyangiitis (Wegener's granulomatosis).

     

Exercise‐induced pulmonary hypertension associated with systemic sclerosis: Four distinct entities

Objective

Exercise‐induced pulmonary hypertension (PH) may represent an early but clinically relevant phase in the spectrum of pulmonary vascular disease. There are limited data on the prevalence of exercise‐induced PH determined by right heart catheterization in scleroderma spectrum disorders. We undertook this study to describe the hemodynamic response to exercise in a homogeneous population of patients with scleroderma spectrum disorders at risk of developing pulmonary vascular disease.

Methods

Patients with normal resting hemodynamics underwent supine lower extremity exercise testing. A classification and regression tree (CART) analysis was used to assess combinations of variables collected during resting right heart catheterization that best predicted abnormal exercise physiology, applicable to each individual subject.

Results

Fifty‐seven patients who had normal resting hemodynamics underwent subsequent exercise right heart catheterization. Four distinct hemodynamic groups were identified during exercise: a normal group, an exercise‐induced pulmonary venous hypertension (ePVH) group, an exercise out of proportion PH (eoPH) group, and an exercise‐induced PH (ePH) group. The eoPH and ePVH groups had higher pulmonary capillary wedge pressure (PCWP) than the ePH group (P < 0.05). The normal and ePH groups had exercise PCWP ≤18 mm Hg, which was lower than that in the ePVH and eoPH groups (P < 0.05). During submaximal exercise, the transpulmonary gradient and pulmonary vascular resistance (PVR) were elevated in the ePH and eoPH groups as compared with the normal and ePVH groups (P < 0.05). CART analysis suggested that resting mean pulmonary artery pressure (mPAP) ≥14 mm Hg and PVR ≥160 dynes/seconds/cm⁻⁵ were associated with eoPH and ePH (positive predictive value 89% for mPAP 14–20 mm Hg and 100% for mPAP >20 mm Hg).

Conclusion

We characterized the exercise hemodynamic response in at‐risk patients with scleroderma spectrum disorders who did not have resting PH. Four distinct hemodynamic groups were identified during exercise. These groups may have potentially different prognoses and treatment options.

     

Autoantibodies against B23, a nucleolar phosphoprotein,occur in scleroderma and are associated with pulmonary hypertension

Objective

To determine whether the abundant nucleolar phosphoprotein B23 is a target of autoantibodies in scleroderma, and to examine the clinical phenotype associated with these antibodies.

Methods

Ninety‐two randomly selected scleroderma sera were screened by enzyme‐linked immunosorbent assay against recombinant human B23. Demographic, clinical, and serologic parameters associated with B23 autoantibody status were examined.

Results

We demonstrated that autoantibodies against B23 occur in ～11% of sera obtained from patients with scleroderma. B23 seropositivity was related to pulmonary hypertension, antifibrillarin antibody, anti‐RNP antibody, and decreased lung capacity. In multivariate analysis, B23 autoantibodies remained strongly associated with moderate‐to‐severe pulmonary hypertension and antifibrillarin antibodies.

Conclusion

These data unite B23 with the group of nucleolar autoantigens targeted in scleroderma and thus focus attention on changes in the nucleolus that render its components immunogenic in this disease. The demonstration that antibodies to B23 are associated with an increased prevalence of pulmonary hypertension points to anti‐B23 antibodies as a possible marker of a specific phenotype in scleroderma.

     

Prospective, open-label, uncontrolled pilot study to study safety and efficacy of sildenafil in systemic sclerosis–related pulmonary artery hypertension and cutaneous vascular complications

Pulmonary artery hypertension (PAH) remains the leading cause of morbidity and mortality in systemic sclerosis, while Raynaud’s phenomenon and digital ulcers significantly add to the morbidity in systemic sclerosis (SSc). This study was undertaken to evaluate the role of sildenafil in PAH, Raynaud’s phenomenon, and digital ulcers in systemic sclerosis patients. A prospective, open-label, uncontrolled pilot study was done at a tertiary care centre in India to study the safety and efficacy of oral sildenafil in PAH, Raynaud’s phenomenon, digital infarcts, and ulcers in SSc. Seventeen patients fulfilling ACR classification criteria for scleroderma and having PAH were recruited. Six-minute walk test, WHO class of dyspnoea, severity of Raynaud’s phenomenon, and 2D ECHO were performed in all the study subjects at baseline and at 3 months post-treatment. All patients were treated with oral sildenafil 25 mg three times a day for a period of 3 months. The pre- and post-treatment values of mean pulmonary artery pressure (PAP), 6-min walk test, WHO class of dyspnoea, and severity of Raynaud’s phenomenon were compared to look for any significant change. Sixteen patients who completed 3-month follow-up had shown statistically significant improvement in 6-min walk test, WHO class of dyspnoea, severity of Raynaud’s phenomenon, and mPAP. Also, there was no occurrence of new digital infarcts or ulcers, and existing ulcers showed signs of healing. Sildenafil is highly efficacious cheaper and safe alternative to other available therapies for SSc-associated PAH, Raynaud’s phenomenon, and digital infarcts/ulcers.     

Hepatopulmonary syndrome and portopulmonary hypertension

Liver disease affects the lungs. The majority of patients exhibit mild to moderate arterial hypoxaemia essentially attributable to an alteration in ventilation/perfusion matching and limited by an increase in ventilation. A minority (some 10%) of patients exhibit a "hepatopulmonary syndrome" defined by severe hypoxaemia with arterial PO2 below 60 mm Hg, dyspnoea, cyanosis, digital clubbing, orthodeoxia, platypnoea and demonstrable pulmonary vascular dilatations causing a true pulmonary shunt and a diffusion/perfusion imbalance. The hepatopulmonary syndrome is incurable but resolves over time after liver transplantation. An even lower proportion of patients, approximately 1%, develop pulmonary hypertension. Clinically this "portopulmonary hypertension" resembles primary pulmonary hypertension, with dyspnoea and fatigue as the main symptoms, histopathology and response to prostacyclin therapy. Portopulmonary hypertension is irreversible. Liver transplantation mortality in patients with portopulmonary hypertension ranges from 50 to 100%. The common cause of the hepatopulmonary syndrome and portopulmonary hypertension is portal hypertension and portosystemic shunting, indicating that vasoactive and angiogenetic factors originating from the liver normally control the pulmonary circulation.     

A Rare Cause of Pulmonary Hypertension: Congenital Bilateral Atresia of the Superior Pulmonary Arteries and Bilateral Stenosis of the Inferior Pulmonary Arteries

Bilateral absence (atresia) of the superior pulmonary arteries, combined with bilateral stenosis of the inferior pulmonary arteries, has not to our knowledge been reported before now. We report such a case in a 48-year-old woman, together with the medical and percutaneous catheter interventions used to treat her condition.Key words: Adult, echocardiography, heart defects, congenital/diagnosis/therapy, hypertension, pulmonary, pulmonary angiography, pulmonary artery/abnormalitiesThe absence of a main branch of the pulmonary artery (PA) was first described by Fraentzel in 1868.¹ The patient who survives to adulthood with this condition usually presents with an abnormal chest radiograph, but with no concomitant cardiovascular abnormalities, with few symptoms, and with any of a variety of erroneous diagnoses.² When pulmonary hypertension is present in the absence of a PA branch, the patient''s condition can be improved by revascularization of the side with the absent artery. In stenotic PAs, intravascular stents have been used to good effect. We report a case of combined bilateral atresia and stenosis, a condition that to our knowledge has not previously been reported. Further, we describe the medical and percutaneous catheter interventions used to treat the patient, and their effectiveness.