Situs inversus total (SIT) entails a mirror-image reversal of all the asymmetrical structures of the body and it is estimated to occur in 1/8000–1/25000 newborns.1 Most patients with SIT lead a completely normal life but, in approximately 20%–25% of patients, associated primary ciliary dyskinesia (PCD) may also be observed.1 PCD, also known as “immotile ciliary syndrome”, is a genetic disease caused by defects of the structure and function of the cilia that lead to abnormal mucociliary clearance which leads to a clinical disease of the sinus and pulmonary regions. Kartagener's syndrome2 (KS), which is currently classified as a subgroup of PCD, is characterized by the triad of bronchiectasis, paranasal sinusitis and SIT.

We present a review of 14 patients with SIT, 11 of whom had KS. In 6 of these patients, there were signs of diffuse bronchiolitis (DB) on thoracic CT. This manifestation associated with KS was first reported in Japan,3 and it still has not been widely accepted. The presence of oligo/azoospermia was observed in 2 of our patients with KS. As far as we know, this is the largest patient series of SIT cases in India.

Over the course of a 7-year period, between April 2003 and March 2010, approximately 11361 new patients (1944 of them from the pediatric age group) with respiratory symptoms were remitted to a unit at our institute. 14 of them (6 males and 8 females; 6 adults and 8 pediatric patients) were diagnosed with SIT. Out of these 14 patients, 11 presented SIT with KS, while 3 only presented SIT (all adult females). The diagnosis of KS was based on the demonstration of the classic triad of the syndrome, consisting of bronchiectasis, paranasal sinusitis and SIT. All patients underwent a similar diagnostic study that included sputum culture for aerobic microorganisms, including Mycobacterium tuberculosis, electrocardiogram, complete spirometry, abdominal ultrasound, computed tomography (CT) with contrast as well as thoracic high resolution CT (HRCT) and CT of paranasal sinuses (PNS). By means of CT, the severity of the bronchiectasis4 and sinusitis5 was evaluated with previously described methods. A semen analysis was done in 2/3 of the adult males who gave their consent.

The clinical characteristics of these 14 patients are indicated, by order of presentation, in Table 1.

Since the moment when it was described for the first time by Kartagener in 4 patients,2 the syndrome that bears his name has fascinated clinicians for the greater part of the last century. Researchers have discovered many associated anomalies, such as diffuse panbronchiolitis (DPB) in KS, which was described for the first time in Japan nearly 2 decades ago.3 Since then, there have only been another 2 reports of this anomaly,6,7 both also originating in Japan. This association has not been described in any other part of the world.

DPB is a very uncommon form of bronchiolitis, characterized by sinus and bronchial inflammation. It has predominantly been observed in Japan, where it was described for the first time in 1969.8 Since then, there have been sporadic publications of cases documented in other Asian countries and also on other continents.9 On HRCT, DPB is characterized in early stages by numerous small nodules (<5mm) that are poorly defined and have centrilobular distribution. In stage 2, some nodules expand, forming small branching linear areas of attenuation (with a “tree in bud” appearance). In the most advanced phases, there is cystic dilation of the nodules that corresponds with bronchiolectasis. The peripheral areas are less dense, and the presence of an expiratory film would suggest air trapping.10 The fact that imaging tests play a key role in the diagnosis of DPB was vehemently emphasized by Hansell11 in the following affirmation: “The HRCT features of diffuse panbronchiolitis, in the appropriate clinical setting, are virtually pathognomonic.”

In 6 of our patients with KS, HRCT showed diffuse small centrilobular nodules with the “tree in bud” pattern, bronchiolectasis/bronchiectasis with tram-tracking indicative of diffuse thickening of the bronchial wall, which were “practically pathognomonic”11 for DPB (Fig. 1). Low attenuation areas were observed, which were accentuated on the images in the lung periphery obtained upon expiration, indicative of air trapping (Fig. 2A and B). These signs that suggest DPB in KS/PCD were initially described in 2 patients by Amitani et al.3 in 1990. They were later seen in 6 out of 8 patients with KS by Homma et al.6 in 1999, and in a patient with KS and a malignant disease7 who had been diagnosed with a DPB 11 years before the presentation.

Fig. 1.

The high-resolution computed tomography (HRCT) of patient number 8 demonstrating dextrocardia, diffuse centrolobulillar nodules with “tree-in-bud” pattern (arrowheads) in the pulmonary periphery with bronquiolectasis/bronquiectasis and diffuse thickening of the bronchial wall (arrow).

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Fig. 2.

Inspiratory (A) and expiratory (B) high-resolution computed tomography (HRCT) of the same patient as Fig. 1. Reduced attenuation of the pulmonary parenchyma in the periphery (arrowheads) is observed, which is accentuated on the expirator image (B) and suggests air trapping. Likewise, the aortic arch on the right side and cystic bronchiectasis in the posterior segment of the right upper lobe can be observed, which presents a reduction in size in the image obtained on expiration (arrow). There are also diffuse centrilobular nodules with “tree-in-bud” pattern and diffuse ectásicos bronchi with thickened walls.

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Homma et al.6 highlighted the notable similarities between KS and DPB with regard to clinical, radiological and spirometric manifestations. Histologically, the inflammatory lesions present in KS were found in the membranous bronchioles, while in DPB they were located in the respiratory bronchioles. The authors proposed that the association of DB could be a “characteristic manifestation”.6 Although the cause of the DPB continues to be unknown, it has been proposed that in PCD the dyskinetic movements of the cilia could cause the appearance of DPB.3,12

Most patients with KS have a favorable prognosis and lead a rather normal life.13 It has been proposed that the ciliary dysfunction leads to a deterioration in ciliary clearance and to the formation of mucus plugs, initially in the small airways and later in the large airways, creating a propensity towards recurring infections that cause bronchiolitis. This leads to air trapping, increased airways resistance, reduced elasticity, hypoxemia, pulmonary hypertension and cor pulmonale. A notable obstruction of the airways was documented in 5/6 patients described by Homma et al.6 and in 4/6 of our patients. In both series, half of the 6 patients with BD presented signs of air trapping on thoracic CT. The appearance of BD in KS could increase morbidity and affect quality of life.

Male patients with KS invariably present infertility, while women present reduced fertility.14 Most infertile patients with KS have a normal spermatozoid count, but with a structural defect and a complete lack of motility.14 Oligospermia and azoospermia are very infrequently observed in KS. However, in our study the semen analysis of the 2 adult patients showed reduced sperm count and motility (oligoasthenozoospermia) in one case and azoospermia in the other. This latter patient presented normal fructose, which suggests the presence of a permeable vas deferens. The presence of azoospermia in KS has previously been reported.15–17 It seems that oligospermia or azoospermia, whose physiopatology has still yet to be defined, can be a variant associated with this syndrome. In addition, some case descriptions have been published of azoospermia obstructiva associated with SIT, which are often labeled as a very uncommon variant of Young syndrome.18,19

We could not determine any anomalies of the dynein arm in our patients, nor did we do any NO nasal inhalado tests. As far as we know, this study documents the largest number of SIT/KS cases in India, and it results for the first time the association of BD with KS in this country.

The authors have no conflict of interest to declare.