Working with argan cake: a new etiology for hypersensitivity pneumonitis

Two cases of documented HP related to handling argan cake were identified among nine exposed workers in a factory using argan cake. Positive diagnosis was based on the presence of the following criteria after specific challenge test at the workplace: presence of suggestive clinical symptoms within 8 hours, significant specific serum antibodies to extracts or argan granulates and non-sterile powder (Precipitins and IgG), significant decrease of DLCO, presence of ground glass opacities (only in subject #4), presence of alveolitis (in both) subjects with mild lymphocytosis (25% in subject #1). Four other patients with suggestive clinical symptoms occurring after argan handling but with no HRCT scan or DLCO changes were considered to present organic dust toxic syndrome, as a significant level of endotoxins (4200 EU/g) was observed in argan cake granulates. Finally, one of these patients presented a lobular emphysema on HRCT scan with altered DLCO, not modified by challenge to argan, and associated with active smoking.

The accuracy of the diagnosis of HP needs to be discussed. In the case index, the combination of symptoms, mild lymphocytosis on BAL, significant decrease of DLCO after challenge with complete recovery in the absence of exposure and the presence of specific serum antibodies with argan granulates or non-sterile powder, appeared to be sufficient to confirm the diagnosis of HP. In absence of lymphocytosis in the second case, the diagnosis of HP may be more doubtful. However, the presence of slight ground-glass opacities on HRCT scan, a significant decrease of DLCO after specific challenge, with recovery in the absence of exposure, as well as significant arcs to antigens derived from argan cake, were clearly in favor of the diagnosis. Moreover, all clinical features were mild and totally reversible after removal from occupational exposure, which could also explain the absence of respiratory crackles on physical examination, as also reported in 32% of patients with form one of the HP study. The positive diagnosis of HP is fairly complex [ 5] and several classifications have been proposed in the literature [ 4, 16- 18]. In most classifications, the major criterion is a combination of suggestive clinical symptoms after exposure to antigens, HRCT abnormalities, specific serum antibodies and lymphocytosis on BAL. However, a decrease in DLCO, positive challenge or inspiratory crackles are considered to be major or minor criteria depending on the classification, and these classifications remain controversial. In particular, a recent study observed that HRCT abnormalities were strongly associated with chronic forms of the disease, but may be absent in more acute forms. Accordingly, we assume that our two patients presented an acute form of HP (or active as proposed by Lacasse et al. in the HP study) [ 4]. Interestingly, the very low frequency of exposure (less than one hour every month for some workers) may explain the paucity and the transient nature of clinical features. The intensity of exposure and repeated exposure are known risk factors for HP [ 19- 21]. The cases described here demonstrate that HP can also occur in very particular circumstances associated with infrequent exposure.

The marked differences between specific serum antibodies against non-sterile forms of argan (both granulate and powder) and sterile forms first suggest that a microbial agent may be responsible for the disease. However, cultures for the microorganisms usually involved in HP were negative, as were specific antibodies for these agents despite the use of several specific media. A review of the literature also found that argan roots are commonly contaminated by Streptomyces marokkonensis [ 10]. As some other Streptomyces spp. are known to be responsible for HP, this may constitute an interesting hypothesis to explain our findings. Unfortunately, all specific serological tests derived from the Streptomyces marokkonensis extract remained negative in all subjects. The last explanation, under the hypothesis of causative microbial agent, is that this agent is a no viable or uncultivable bacteria or fungi. However, these negative results and the fact that, to the best of our knowledge, HP has never been previously described in the literature among workers (mainly women) of argan cooperatives, also suggest that the antigen responsible could be a protein. In this case, differences observed between specific serum antibodies against argan granulates and powder and against the sterile form could be explained by a heat-labile protein. Further investigations are required to identify the protein or microbial agent responsible for the HP observed in these two patients.