C. botulinum is an anaerobic, spore-forming, Gram-positive bacillus [2, 6]. Its spores are commonly present in soil, household dust, and agricultural products [8]. They are resistant to boiling and cooking and are often ingested by humans, however, they do not normally germinate in the intestine [1].

Botulinum toxins are produced by C. botulinum and related species and are considered the most powerful biological toxins known [1, 4]. There are 9 different types of BoNTs, but only 4 (A, B, E, and F) are associated with human botulism [2, 6]. BoNTs can reach the bloodstream in several ways. Based on the entering route of the toxin, different forms of botulism can be distinguished, such as foodborne botulism, iatrogenic botulism, wound botulism, and inhalational botulism, which is due to exposure to aerosolized BoNTs, possibly associated with occupational settings or bioterrorism [1, 3, 4, 6]. Significantly, the same type of C. botulinum that affected the patient has been discovered in household dust in instances of IB [9, 18, 19]. In the case we reported, botulism was likely acquired through inhalation of BoNT-laden dust particles generated through home renovation works. Dilena et al. reported a similar case of IB in a six-month-old infant, exclusively breastfed, whose father was a carpenter involved in home renovation [6].

Another form of botulism is intestinal toxemia, characterized as IB when it affects children under one year of age [6, 20, 21]. Unlike foodborne botulism, which results from the accidental ingestion of the preformed toxin, intestinal toxemia is due to spore germination, toxin production and colonization of Clostridia in the large intestine [2, 3, 6].

The synthesis of BoNTs includes several steps. The progenitor toxin releases a single-chain polypeptide in the upper small intestine, which, in turn, is cleaved in two subunits: a heavy chain (H-chain) and a light chain (L-chain) [8]. The H-chain binds to membrane glycoproteins of the presynaptic membrane at the neuromuscular junction, leading to the endocytosis of the L-chain, which blocks the release of acetylcholine in the synaptic space [1, 2, 8]. The outcome is therefore flaccid paralysis and extremity weakness [2]. Since the intestinal smooth muscles are the first to be affected, constipation is an early sign [2]. Head, facial and throat musculature is also affected early on for circulatory reasons, with subsequent bulbar palsy [8]. What follows is a descending flaccid paralysis of voluntary and autonomic muscles, potentially leading to respiratory failure [1,2,3].

Signs and symptoms of botulism can last from hours to a few days and occur after an incubation period spanning from 12–36 h to 10 days [1, 2, 8, 22].

The clinical picture can range from a mild syndrome, with poor feeding, dry mouth, constipation and drowsiness resolving over a few days, to severe hypotonia and respiratory failure [2, 8]. Three phases can be distinguished: (a) a descending paralysis lasting two weeks, (b) a phase of minimum muscle function of the same duration, and (c) a slow, lengthy muscle-recovery phase [6, 7]. Initial manifestations include ptosis, flat expressivity, weak cry and drooling; hypotonia, loss of head control and paralysis follow; respiratory paralysis can occur at last, with a mortality rate of 1% [1, 2]. Since mydriasis could also be a sign in infants, and it is not always promptly noticeable, it is advisable to repeat the pupillary test for two minutes [8].

Recovery occurs through regeneration of nerve axons, leading to motility restoration [2, 20]. In order to ward off the risk of aspiration, patients should be discharged only when they are gagging, sucking and swallowing effortlessly [2, 8]. Complications of IB include hypoxic brain injury, cardiac arrest, syndrome of inappropriate antidiuretic hormone secretion (SIADH), urinary tract infections due to indwelling bladder catheters, septicemia associated with intravascular catheters, and pneumonia [2, 8].

Both clostridia and toxins can be found in the feces of infants for weeks or months after symptoms resolution [2, 8].

Considering the rarity of botulism and the lack of clinical specificity, it is unsurprising that the diagnosis is often delayed or missed [1]. This condition should be considered in all hypotonic infants with feeding difficulties, ptosis and constipation [2, 6].

Diagnosis can be confirmed through the identification of C. botulinum or BoNTs in microbiological samples, such as serum or stools [2, 6]. Toxin identification takes about 48 h, while culture of Clostridia requires more than 5 days [2].

The Italian CNRB uses polymerase-chain reaction (PCR) together with the standard mouse bioassay method to confirm the diagnosis of botulism [17].

Possible differential diagnoses include drug intoxication, sepsis, which is the most frequent misdiagnoses upon admission, metabolic disorders, and neurologic conditions such as Guillain Barré Syndrome (GBS), encephalitis, meningitis, and spinal muscular atrophy (SMA) type 1 [1, 6, 8].

Blood tests, cerebrospinal fluid exam, and imaging investigations are non-specific but can be helpful to manage the complications and to exclude other diagnoses, such as sepsis, meningitis and dehydration [2]. Nerve conductions studies and electromyography can reinforce the clinical suspicion while waiting for the microbiological confirmation [2, 6].

Treatment consists of supportive care, including respiratory and nutritional support, and administration of the botulinum antitoxin, which decreases mortality and length of hospital stay [1, 20]. The antitoxin should be administered as soon as possible even if the diagnosis has not been confirmed and, in case of progressive paralysis, it should always be administered regardless of the time of symptom onset [1, 2]. If neurologic signs persist 24 h from the administration of antitoxin, alternative diagnoses should be considered [1]. While the antitoxin cannot reverse paralysis, it neutralizes toxins that are not yet bound to synaptic receptors [1].

Human intravenous botulism immunoglobulin (BIG-IV) is the gold standard treatment for IB, while the equine botulinum antitoxin (EqBA) can be considered as an alternative [2]. BIG-IV consists of IgGs able to neutralize type A and type B BoNTs [23]. Its recommended dosage is 50 mg/kg and it should be administered only once, intravenously [2]. On the other hand, EqBA is derived from horses hyperimmunized with BoNTs [2]. In 2010, a botulism antitoxin heptavalent (BAT) formulation neutralizing 7 BoNT serotypes was approved and licensed by the Food and Drug Administration (FDA) [1]. In Europe, the BAT and the trivalent botulinum type A + B + E antitoxin are the most commonly used for botulism forms other than IB [2]. The equine antitoxin is associated with the risk of anaphylaxis and lifelong sensitization to equine proteins; epinephrine and antihistamines should be readily available at the time of administration [1]. Practical details of the treatment with antitoxins are described in Table 1.

Mechanic ventilation should be considered when swallowing and gagging are compromised in order to prevent respiratory arrest and hypoxic encephalopathy [1, 8]. Nutritional support through a nasogastric tube promotes peristalsis and the elimination of Clostridia [8].

Thanks to modern intensive care techniques, mortality rates have been decreasing over the past decades and patients who receive adequate supportive care can recover completely even without the administration of the antitoxin [1]. Of note, Nevas et al. reported a case of IB characterized by its presentation with sudden infant death syndrome (SIDS) [28]. The infant passed at 11 weeks and C. botulinum was found in his intestinal content and in dust collected from his household [28].

Antibiotic treatment is not recommended for IB for several reasons: (1) lysis of bacteria could increase the amount of free toxin in the colon, (2) the intestinal flora may be altered in a way that facilitates the growth of Clostridia, and (3) aminoglycosides may enhance neuromuscular block [1, 3, 8, 29].

The reported case is, to the best of our knowledge, the first case of IB observed in Sicily. The subtle clinical presentation observed in this case demonstrates the importance of clinical suspicion in diagnosing IB. It is advisable to consider this condition in every infant with rapidly progressing hypotonia and a history of constipation.

The peculiarity of this case lies in the mode of transmission of the disease, which likely consisted of toxin inhalation. Considering that honey consumption had been ruled out during anamnesis, botulism originally seemed an unlikely occurrence. However, a more thorough and careful consideration of all the potential sources of BoNTs led to the correct diagnosis. Our experience highlights the importance of taking a detailed medical history when IB is suspected, inquiring not only on honey consumption, but also on the possible exposure to construction work dusts or contaminated water or soil. Physicians should be aware that infants could accidentally inhale toxins from domestic or soil dusts or carried by relatives who work in building sites.

Furthermore, our case shows how a timely diagnosis signifies the administration of life-saving treatment.