Description 

A 41-year-old Japanese man with no underlying disease was admitted to our hospital with haemoptysis and dyspnoea. Two weeks prior to admission, he had caught a cold and took an over-the-counter drug (topikku GX), subsequently general fatigue and cough were worsening progressively. Hence, he presented to another hospital, owing to acute onset of dyspnoea on effort and haemoptysis, where chest X-ray was taken and revealed bilateral abnormal shadow in the middle lung fields, after that he was referred to our hospital.

On examination, his general appearance was moderately ill; blood pressure was 126/72 mm Hg, heart rate was 90 beats/min, oxygen saturation was 90% under ambient air, respiratory rate was 20 breath/min and body temperature was 38.2°. Chest auscultation revealed bilateral inspiratory mid to late crackles. Laboratory blood test showed mild elevation of liver function tests (Aspartate aminotransferase 42 IU/L, Alanine aminotransferase 34 IU/L), Lactate dehydrogenase 379 IU/L, C-reactive protein 28.2 mg/L, the rest of the result including serological tests for infectious agents and autoimmune diseases were within normal limit.

Chest CT revealed bilateral non-segmental diffuse gland-glass opacities and reticular shadows extending from upper to lower lung fields (figure 1).

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Figure 1

Chest CT on admission shows diffuse areas of ground-glass opacity.

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Figure 2

Lung biopsy shows prominent diffuse hyaline membranes in alveolar lumens and alveolar haemorrhage confirmed by bronchoalveolar lavage on admission.

We performed bronchoscopy on admission day and bronchoalveolar lavage of the affected area revealed haemorrhagic findings with an increasing red cell count, and lung biopsies showed necrosis of alveolar lining cells with extravasation of fibrin (figure 2). We diagnosed drug-induced diffuse alveolar damage (DAD). The over-the-counter drug was discontinued and administration of corticosteroid made his symptoms relieved rapidly, leading to gradual tapering and then off. Finally, we performed drug lymphocyte stimulation test for the drug with exhibiting strong positive.

Though precise incidence of drug-induced lung injuries has not been accurately determined, recently the report of drug-induced lung injuries in Japan has increased since 2000.1 DAD has the tendency to lower response to therapy and poor prognosis.2 It has been reported that many kinds of drugs can cause drug-induced lung injuries; however, some types of drugs such as cytotoxic agents and molecular targeting drugs may lead to trigger DAD.3 In addition, as for diffuse alveolar haemorrhage, it has been also reported that various types of medications can cause diffuse alveolar haemorrhage, such as propylthiouracil, chemotherapy agents, anticoagulants and thrombolytic agents. Generally speaking, drug-induced DAD, which is caused by cytotoxic mechanisms, may not respond to corticosteroids2; however, the patient responded to corticosteroids dramatically and chest radiograph returned to normal on fourth hospital visit. topikku GX  is mainly composed of eight types of ingredients and addictives. There have been reports of lung injuries derived from ingredients of which topikku GX is composed. These ingredients are acetaminophen, chlorpheniramine, ephedrine niu-huang and dihuang. Most of the pathogenetic mechanisms by which drugs induce lung injuries are unknown. To the best of our knowledge, none has reported that ‘over-the-counter drug’ induced lung injuries exhibiting both diffuse alveolar haemorrhage and DAD (table 1). We should be careful about drug-induced injuries leading to life-threatening state when respiratory symptom is rapidly worsening after taking medicine including over-the-counter drugs.