2001 - A Lady with Rash and Hypoxemia
Dr WM Chan, Intensive Care Unit, Yan Chai Hospital
Case History
The patient was a 46 year old lady who was well until she presented to the Medical Unit of YCH in May 2000 when she complained of fever for 2 weeks. She noted chills and rigors and polyarthralgia involving both large joints and small joints of both hand. She had a facial rash but her GP ascribed it to drug allergy. She had a dry cough but was otherwise well. She had no history of travel. Physical examination at the initial admission was normal, except that aphthous ulcers were noted over the tongue and the proximal inter-phalangeal joints of both hands were slightly swollen. Initial work up showed that the patient had a normochromic normocytic anaemia with depressed reticulocyte count. There was a mild lymphopenia (lymphocytes 0.75x 109/L) and a raised ESR of 52 mm/hr. Biochemistry showed raised transaminases with an ALT of 307 U/L and AST of 283 U/L. The creatine kinase was also elevated at 389 U/L. The admission chest radiograph was entirely normal. Because of the persistent fever that was refractory to empirical treatment by Clarithromycin, workup as for pyrexia of unknown origin was started, as shown in Table 1.
CT scan of Abdomen and Pelvis (28 June 2000) showed no abnormal lesions, no lymphadenopathy and only simple liver cysts. The CT thorax with intravenous contrast followed by HRCT Thorax in supine and prone positions were done on 28 June 2000. That showed subsegmental consolidation over both mid zones at lung periphery. The lower lobes showed parenchymal scarring with distorted architecture and bronchiectasis. There were no lymphadenopathy, no pleural effusion and no nodules. Features were non-specific, and was reported as: "Chronic changes with fibrosis and some acute lesion, Ddx: Interstitial Pneumonia, ? Early desquamative or usual interstitial pneumonia"
Blood gas checked for the first time on 28 June 2000 on room air revealed pH 7.57, PaCO23.48 kPa and PaO2 12.01 kPa.
The skin rash noted at the initial admission was subsequently biopsed and reported on 4 July 2000. It showed features compatible with Dermatomyositis and no features of vasculitis. It was decided to start on Prednisone under cover with antibiotics including Roxithromycin and Piperacillin/Tazobactam. The fever was not responding. Without response, the patient received empirical pulse Methylprednisolone therapy at 1 gram daily for 3 days from 10July 2000.
Blood gas repeat on 10/07/00 showed hypoxaemic failure with pH 7.5, PaCO2 4.32 kPa and PaO26.25kPa. CT pulmonary angiogram was done on 10th July 2000 that showed no major vessels embolus. A concomittent conventional CT of thorax (Figure 1) showed peripheral alveolar shadows over subpleural areas.
The ICU team was consulted when the patient develop worsened desaturation. The patient was taken over to the ICU on 13 July 2000. It was decided for an urgent open lung biopsy after diagnostic fibreoptic bronchoscopy. Endoscopy showed some whitish plaques at bronchus intermedius and distal L main bronchus. Biopsy of the material was reported as "necrotic material". BAL showed no organisms on Gram smear and ZN stain. Cytology was negative, including search for Pneumocystis carinii. All subsequent cultures were also negative.
Chest radiograph on the day of biopsy was shown (Figure 2).
A wedge biopsy via thoracoscopy was performed after intubating the patient: It was subsequently reported to show "Organizing Pneumonia" with no features of BOOP.
A muscle biopsy at the L deltoid taken on the day before ICU admission was reported
on 17July 2000. It showed:
• Occasional atrophic fibres among normal fibres
• Focal fibres necrosis, with infiltration by mononuclear lymphohistiocytic cells.
• No vasculitis or features of muscular dystrophy.
Features were consistent with Polymyositis.
With the results of the skin biopsy, the diagnosis of the pulmonary condition was thus Dermatomyositis with interstitial lung disease.
With the patient developed worsened oxygenation failure with negative cultures, it was decided for an empirical trial of Intravenous Immunoglobulins starting 17 July 2000. The oxygenation failure got worse and the patient required increasing PEEP and FiO2up to 100%.A desperate trial with cyclophosphamide was given. Nebulized prostacyclin (Iloprost) was started as an attempt to reverse the hypoxaemic failure. There was a transient improvement of oxygenation when Iloprost was nebulized up to 20ng/kg/min, but eventually the patient still succumbed because of intractable oxygenation failure on 22 July 2000.
Discussion
Interstitial Lung Diseases in Patients with Dermatomyositis
Interstitial lung diseases have been well describe in patients with dermatomyositis and polymyositis. The incidence was estimated to be 5-9% in patients with Dermatomyositis. The disease spectrum had been reviewed by Tazelaarl on 15 patients with interstitial lung disease confirmed on open lung biopsy. Essentially they fall into 3 basic categories:
1. Usual interstitial pneumonia (UIP)
2. Bronchiolitis obliterans organizing pneumonia (BOOP), which is associated with the best prognosis, and
3. Diffuse alveolar damage (DAD).
The antisynthetase, particularly Anti-histidyl RNA synthetase, or Anti-Jo 1 Antibody, were markers of interstitial lung disease in patient with Dermatomyositis / Polymyositis. In our patient, however, the Anti-ENA screen was negative.
Systemic corticosteroids are generally recommended for the treatment2, but addition of other immunosuppresives had been controversial. The early use of combination cyclophosphamide with systemic steroids has been reported to be beneficial. IV immunoglobulin3,in combination with cyclosporin, has also been shown in a randomized trial that might induce remission in patients with steroids resistant dermatomyositis. In spite of the use of all these agents, our patient still deteriorated and died.
Use of Selective Pulmonary Vasodilators for Hypoxaemic Respiratory Failure
Selective pulmonary vasodilators, particularly nitric oxide, received great attention in the past few years in the hope that it might help improving oxygenation in patients with severe hypoxaemic respiratory failure. The ideas have been attractive in that these vasodilators, when given by inhalation or as an aerosol, presumably dilates only pulmonary vessels that are were well ventilated. Thus there were preferential blood flow to areas with adequate ventilation, thus improving ventilation/perfusion matching.
The use of nitric oxide has been well studied in patients with acute respiratory distress syndrome (ARDS). Three randomized control trials4,5,6, however, showed that while nitric oxide improves oxygenation within the first 24-48 hours after initiation, the benefits were not sustained. The interest for its use thus died down. Prostacyclin is a potent vasodilator and it has also potent anti-thrombotic activity by decreasing platelets adhesion. Nebulized prostacyclin has been studied in patients with ARDS and primary pulmonary hypertension. In patients with hypoxaemic respiratory failure due to primary pulmonary hypertension, intravenous and aerosolized7 Prostacyclin has been shown to improve oxygenation and improve exercise tolerance.
Aerosolized prostacyclin has been studied in patients with ARDS. The advantage of using aerosolized prostacyclin lies partly in the fact that no major setup or equipment is needed, unlike the setting for inhaled nitric oxide. Prostacyclin was infused by a syringe driver into the nebulizer port of the ventilator. Nebulized prostacyclin has been compared to Inhaled nitric oxide in patients with ARDS and was considered to be of similar efficacy in improving oxygenation8. Aerosolized prostacyclin has not been shown to improve survival outside the settings of primary pulmonary hypertension.
Thus, use of selective pulmonary vasodilators, such as nitric oxide and aerosolized prostacyclins, are not recommended in general for pulmonary hypertension associated with hypoxaemia, except for primary pulmonary hypertension. It might be considered a salvage therapy if a very reversible pulmonary condition is being treated, or while the patient is expected to receive lung transplant in the very near future.
References
- Tazelaar HD, Viggiano RW, Pickers gill J, Colby TV. Interstitial lung disease in polymyositis and dermatomyositis. Am Rev Respir Dis 1990; 141:727-733.
- C. Lamblin C, Bergoin C, Saelens T, Wallaert B. Interstitial lung diseases in collagen vascular diseases. Eur Respir J 2001; 18:SuppI32, 69s-80s.
- Saadeh C, Bridges W, Burwick F. Dermatomyositis: remission induced with combined oral cyclosporine and high-dose intravenous immune globulin. South Med J 1995; 88:866-870.
- Dellinger RP, Zimmerman JL, Taylor RW and the Inhaled Nitric Oxide in ARDS Study Group. Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a randomized phase II trial. Crit Care Med 1998; 26: 15-23.
- Troncy E, Collet J-P, Shapiro S, Guimond J-G, Blair L, Ducruet T, et al. Inhaled nitric oxide in acute respiratory distress syndrome: a pilot randomized controlled study. Am J Resp Crit Care Med 1998; 157:1483-1488.
- Michael JR, Barton RG, Saffle JR, et al. Inhaled nitric oxide versus conventional therapy: effect on oxygenation in ARDS. Am J Resp Crit Care Med 1998; 157:1372-1380.
- Hoeper MM, Schwarze M, Ehlerding S, et al. Long-term treatment of primary pulmonary hypertension with aerosolized Iloprost, a prostacyclin analogue. N Engl J Med 200; 342:1866-1870.
- Walmrath D, Schneider T, Schermuly R , Olschewski H, Grimminger F and Seege W. Direct comparison of inhaled nitric oxide and aerosolized prostacyclin in acute respiratory distress syndrome Am J Respir Crit Care Med, 1996; 153:991-996.
