SJS is known as mucocutaneous ocular syndrome and causes severe erythema exsudativum multiform . The syndrome is caused by many drugs, including antibiotics or antiepileptic, as well as by infection such as viruses or mycoplasma . The pathogenesis of chronic pulmonary disorders such as BO in SJS remains obscure. BO is a rare disease in which granulation tissue mainly obliterates the lumen of the membranous bronchioli. It is useful to diagnose as having BO clinically based on mosaic appearance on chest CT images or small airway obstructive impairment on pulmonary function test, but as confirmed diagnosis of BO requires lung specimens obtained by video-assisted thoracic surgery or autopsy, it may be difficult to make a correct antemortem diagnosis. Theegarten et al.  reported that diagnosis of interstitial pneumonias, a group of quite rare diseases, by open lung biopsies required sufficient clinical information because of the overlap of histological patterns and especially in non idiopathic interstitial pneumonias, an interdisciplinary case evaluation was needed. Therefore, we believe it is necessary to find a correct diagnosis histologically. More recently, Griff et al.  reported that specimens obtained by transbronchial cryobiopsy technique were significantly larger than those by conventional transbronchial biopsies, in addition the alveolar tissue of cryobiopsy specimens did not show any artifacts. This technique may be useful for the diagnosis of BO.
Yamanaka, et al.  conducted a histopathological study of BO associated with rheumatoid arithritis or SJS, and proposed bronchobronchiolitis obliterans (BBO) as the pathological condition in which the BO lesions were seen from the small bronchi to membranous bronchioli. A small number of BO cases caused by drug-induced SJS which were histologically confirmed have been reported so far [7–9]. As reported by Tsunoda, et al. , autopsied lung in BO associated with SJS showed macroscopically airway obliterations were located in the 3rd and 5th branches, numbering from each lobar bronchus. Histological examination revealed loss of bronchial epithelium and narrowing or obliteration of the bronchiolar lumen due to proliferation of granulation tissue not only in membranous bronchioli but also cartilaginous bronchi. In the present case, macroscopic appearances showed extensive occlusion of the bronchi at the 4th or 5th branches, which were located in more distal bronchi than each segmental bronchus. Histologically, the bronchial wall structure such as the smooth muscle layer and the elastic fiber layer was maintained, and the airway lumen was markedly occluded due to fibrous tissue, suggesting constrictive BBO. Interestingly, the BO lesions were sporadically and intermittently located from the small bronchi to the membranous bronchioli. On the other hand, bronchiectasis and the bronchial wall structures were completely destroyed and replaced by fibrous tissue in the right middle lobe and in both lower lobes in our case. We speculated that after SJS caused constrictive BBO throughout most of the lungs, bacterial infection such as Pseudomonas aeruginosa, etc. induced inflammations in the airways repeatedly, resulting in bronchial mucosal ulcers, bronchiectasis and bronchiolectasis during the following 17 years. Hebisawa, et al.  histopathologically searched for patients who died of diffuse bronchiectasis associated with chronic respiratory infections, and found destructive BO showing complete destruction of the bronchiolar wall structures and its lumen replacement with collagen fibers.
The pathogenic mechanism of BO in SJS is not well understood, but we believe that BO in SJS appears as a consequence of bronchiolar epithelium and mucosal damage due to immune complex deposition in SJS. Furthermore, the combination of the immune response abnormality and respiratory infection may play an important role in its development. According to previous reported cases, respiratory symptoms appeared within a few weeks to months after mucosal or skin symptoms improved. Also in the present case, respiratory symptoms appeared 2 months after treatment with large amounts of corticosteroid for SJS. We assumed that some kind of injuries to bronchiolar epithelial cells initiate its changes in necrosis and shedding of them, and then followed exudation of the fibrin and inflammatory cells such as lymphocytes, macrophages, and proliferation of the myofibroblasts and capillary vessels. Finally, the bronchiolar lumens were obliterated by fibrous granulation tissue. Therefore, it is considered that formation of BO requires certain intervals after the onset of SJS. However, the mechanisms of selective damages to mainly membranous bronchioli in BO remain obscure. Recently, Nicod  described that using heterotopic tracheal transplant models with mice obliteration of airway lumen may result from the overactivation of repair mechanisms by fibroblasts in damaged bronchioli and progressive structural reconstruction (remodeling) or fibrosis around the lesions. On immunohistochemical study of the present case, CD3-, CD20-, CD68-, and TGF-β positive cells were found partly but prominent SMA-positive cells infiltration in the BO lesions. In fact, the differences in the disease duration of BO or the immunocompromised state of the host associated with treatments or underlying disorders will influence the extent of inflammatory cells and myofibroblasts. Finally, production of growth factors such as TGF-β which promote fibroblast proliferation may result in fibrosis at late phase of BO formation. In addition, Shah et al.  reported that a case of constrictive BO and eosinophilic micro-abscesses after SJS. It is known that eosinophils are important sources of a variety of pro-fibrogenic mediators such as TGF-α , TGF-β , vascular endothelial growth factor , and interleukin-13 . Although eosinophils were not found in the BO lesions at autopsy in the present case, increased eosinophils could be determined at an earlier stage of BO.