# Emerging Mycotoxic Syndromes in France: Epidemiological Trends and Public Health Implications (2015–2022)

Chloé Bruneau, Manon Poilane, Jérémy Lecot, Anne Landreau, Gaël Le Roux

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Chloé Bruneau, Manon Poilane, Jérémy Lecot, Anne Landreau, Gaël Le Roux. Emerging Mycotoxic Syndromes in France: Epidemiological Trends and Public Health Implications (2015–2022). Toxicon, 2025, 268, pp.108623. 10.1016/j.toxicon.2025.108623. hal-05319639

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# Emerging mycotoxic syndromes in France: Epidemiological trends and public health implications (2015–2022)

Chloé Bruneau<sup>a</sup>, Manon Poilane<sup>a</sup>, Jérémy Lecot<sup>a,●</sup>, French PCC research group, Anne Landreau<sup>b,c</sup>, Gaël Le Roux<sup>a,d,*</sup>

## ARTICLE INFO

Handling Editor: Ray Norton

**Keywords:**

Mushroom poisoning

Morel neurotoxic syndrome

Flagellate dermatitis

Amanita proxima poisoning

Emerging mycotoxic syndromes

Rhabdomyolysis

## ABSTRACT

Mushroom poisoning is a common cause of toxic exposure, and several “new mycotoxic syndromes” have been recognized since the 1990s. We conducted a retrospective multicenter study using the French Poison Control Centers cases database to describe their epidemiology in mainland France between 2015 and 2022. Cases involving species known to cause one of the seven « new » syndromes were included. Overall, 275 cases were identified, accounting for 1.7 % of the 2000 mushroom poisonings reported annually. Four syndromes were observed: neurotoxic morel syndrome (n = 159, 57.8 %), flagellate dermatitis (n = 110, 40.0 %), *Amanita proxima/smithiana* poisoning (n = 4, 1.5 %), and rhabdomyolysis (n = 2, 0.7 %). Most cases were mild (78.2 %), with 21 % moderate and 0.7 % severe. No cases of acromelalgic syndrome, *Hapalopilus nidulans* encephalopathy, or convulsive encephalopathy were recorded. Clinical features matched prior descriptions, with atypical presentations documented, including rare ocular sequelae after *A. proxima* ingestion and unusual neurological signs in morel poisoning. A pronounced April peak (42.2 %) coincided with morel season. Emerging mycotoxic syndromes remain infrequent but are increasing in relative frequency, driven mainly by morel-related neurotoxicity and shiitake dermatitis. Findings support strengthened toxicovigilance and clear public guidance: correct cooking of morels/shiitake, caution against confusion with toxic look-alikes, and expert identification when in doubt. Beyond France, countries with strong foraging traditions may face similar risks and should adapt surveillance and prevention accordingly.

## 1. Introduction

Poisonings resulting from the ingestion of wild mushrooms are common and occur in all regions of the world. While the toxicity of certain species has been well characterized for decades, the concept of “emerging mycotoxic syndromes” was proposed in the 1990s and encompasses seven clinical entities: flagellate dermatitis syndrome (Nguyen et al., 2017), morel-related neurotoxic syndrome (Saviuc et al., 2010), *Amanita proxima/smithiana* poisoning (Diaz, 2021), rhabdomyolysis syndrome (Lee et al., 2001), acromelalgic syndrome (Mizusawa and Shimizu, 2021), *Hapalopilus nidulans*-induced encephalopathy (Villa et al., 2013), and convulsive encephalopathy due to *Pleurocybella porrigens* (Kato et al., 2004).

These syndromes share several features: (i) a latency usually longer

than 6 h, (ii) a simultaneous but geographically distant emergence, and (iii) prolonged investigations, sometimes extending over several years, before their nosological identity was established. “Emerging mycotoxic syndromes” can be classified into two groups: (i) those linked to species with newly recognized toxicity despite prior reputation of edibility (e.g., morels, shiitake, *Tricholoma equestre*); and (ii) those due to toxic species initially confused with edible mushrooms (e.g., *Amanita proxima* / *smithiana*). The causative species and clinical features of these syndromes are detailed in Table 1.

Before 2015, published data on emerging mycotoxic syndromes in France were limited to isolated case reports and small case series, mainly concerning shiitake dermatitis (Boels et al., 2014), morel-related neurological clusters (Saviuc et al., 2010), or rare observations of *Amanita proxima* poisoning (de Haro et al., 1998). The national

<footnote><sup>a</sup> "Grand Ouest" Poison Control Center, University Hospital of Angers, 4 Rue Larrey, F-49933, Angers 9, France</footnote>

<footnote><sup>b</sup> University of Angers, Faculty of Health, F-49000, Angers, France</footnote>

<footnote><sup>c</sup> University of Angers, University of Brest, IRF, SFR ICAT, F-49000, Angers, France</footnote>

<footnote><sup>d</sup> University of Angers, CHU Angers, University of Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail) - UMR_S1085, Angers, France</footnote>

<footnote>* Corresponding author. "Grand Ouest" Poison Control Center, University Hospital of Angers, 4 Rue Larrey, F-49933, Angers 9, France.
E-mail address: galeroux@chu-angers.fr (G. Le Roux).</footnote>
incidence of these syndromes was therefore unknown, although preliminary reports suggested they accounted for <2% of mushroom poisonings. Their public health relevance lies in the fact that they may involve species widely perceived as edible, leading to unexpected toxic effects in the general population.

The incidence of mushroom poisoning cases appears to be higher in regions with active foraging traditions, underscoring the cultural significance of mushrooms in countries like Poland and Italy compared to others, such as the UK, where foraging is less common (Wennig et al., 2020; Smědra et al., 2022). France has a longstanding cultural tradition of fruits and mushroom foraging, with an estimated 1 in 4 adults engaging in the practice annually, particularly in rural and forested areas (Lovrić et al., 2021). In parallel, exotic mushrooms such as shiitake (Lentinula edodes) are increasingly available through supermarkets, short food supply chains, and online sales, introducing new patterns of exposure (Boels et al., 2014). Regulatory measures have also shaped

consumption (Peintner et al., 2013): for example, the sale of *Tricholoma equestre* has been prohibited in France since 2005 (Decree No. 2005–1184), following reports of fatal rhabdomyolysis.

Climate warming is already impacting fungal phenology and distribution in France, with Mediterranean and open habitats being particularly affected (Gautier et al., 2022). As temperatures rise and droughts become more frequent, these regions are likely to undergo rapid changes in fungal composition. The recent emergence of *Chlorophyllum molybdisites* in Europe (Negrini et al., 2022), a toxic mushroom species native to tropical regions, illustrates this climate-driven redistribution, as species previously restricted to warmer climates are now able to establish themselves in temperate zones.

Due to their relatively recent recognition and the limited number of isolated cases, these syndromes have been the subject of only a few publications in the form of case series. This national focus is justified by the high incidence of mushroom consumption in France compared to

<table><caption>**Table 1**

Description of emerging mycotoxic syndromes.</caption><thead><tr><th>Mycotoxic syndrome</th><th>Involved species (Eysyartier and Roux, 2017; MNHN, 2025; Société mycologique de France, 2025)</th><th>Probable toxins Mechanism of action</th><th>Delay, clinical presentation, duration</th><th>References</th></tr></thead><tbody><tr><td>Rhabdomyolysis</td><td>Tricholoma equestre (L.: Fr.)<br/>Kumm. (syn. Tricholoma flavovirens sens. auct.)<br/>Tricholoma auratum (L.: Fr.) Gillet (syn. Tricholoma equestre sens. auct.)<br/>Russula subnigricans Hongo</td><td>Unknown mycotoxin for Tricholoma spp.; cycloprop-2-ene carboxylic acid and 6 chlorophenyl ethers (russupheline A-F) for R. subnigricans</td><td>Delay: 1–6 days after 3–6 successive meals<br/>Asthenia, profuse sweating without fever, muscle weakness and myalgias<br/>Rhabdomyolysis and renal failure of variable severity</td><td>(Takahashi et al., 1993; Bedry et al., 2001; Sein Anand and Chwaluk, 2010; Lin et al., 2015; Matsuura et al., 2016)</td></tr><tr><td>Acromelalgic syndrome</td><td>Paralepistopsis acromelalga (Ichimura) Vizzini (syn. Clitocybe acromelalga), P. amoenolens (syn. Clitocybe amoenolens [Malençon] Vizzini)</td><td>Acromelic acids type A (structure similar to domoic and kainic acids)<br/>Potent agonists of non-NMDA glutamatergic receptors</td><td>Average duration: 2 weeks<br/>Delay: ~24 h<br/>Erythromelalgia: paresthesias and very painful burning sensations (with edema and erythema) of hands and feet, evolving in paroxysmal nocturnal crises<br/>Duration: 8 days to 5 months (some cases with residual paresthesias)</td><td>(Bessard et al., 2004; Saviuc and Danel, 2006; Saviuc and Moreau, 2012)</td></tr><tr><td>A. proxima/ smithiana poisoning</td><td>Amanita proxima Dumée (Europe)<br/>Amanita smithiana Bas (North America)<br/>Amanita pseudoporphyrina Hongo (Asia)</td><td>2-amino-4,5-hexadienoic acid (allenic norleucine)<br/>Hypothesis: necrosis of renal epithelial tissue</td><td>Delay (digestive phase): 8–14 h (nausea, vomiting, diarrhea)<br/>Delay (hepato-renal phase): 1–4 days (acute tubulo-interstitial nephropathy, moderate cytolysis)<br/>Average duration: 20 days</td><td>(Pelizzari et al., 1994; Saviuc, 2009; Adibelli et al., 2024)</td></tr><tr><td>Neurotoxic syndrome</td><td>Morchella esculenta (L.: Fr.) Pers. (syn. M. rotunda)<br/>Morchella deliciosa Fries (syn. M. conica)<br/>Morchella elata Fries<br/>Morchella vulgaris (Persoon) Gray</td><td>Unknown mycotoxin<br/>Ingestion of raw, undercooked or over-eaten morels</td><td>Average duration: 20 days<br/>Delay (digestive symptoms): 6–12 h (abdominal pain, vomiting, diarrhea)<br/>Delay (neurological signs): 12–24 h (tremors, dizziness, inebriation, ataxia, headache, confusion, polymorphic ocular disturbances)<br/>Average duration: 12–24 h</td><td>Saviuc et al. (2010)</td></tr><tr><td>Flagellate dermatitis</td><td>Lentinula edodes (Berk.)</td><td>Unknown mycotoxin<br/>Hypothesis: lentinan<br/>Promotes inflammation</td><td>Delay to first symptoms: 12 h–5 days<br/>Inconstant digestive symptoms (early phase)<br/>Pruritic, whip-like linear eruptions.<br/>Average duration: 2 weeks</td><td>(Boels et al., 2014; Netchiporouk et al., 2015)</td></tr><tr><td>H. nidulans encephalopathy</td><td>Hapalopilus nidulans (Fr.: Fr.) P. Karst. (syn. H. rutilans)</td><td>Polyporic acid (dihydroxyquinone)<br/>Inhibition of pyrimidine base synthesis</td><td>Delay to first symptoms: 6–12 h<br/>Digestive symptoms: nausea, vomiting, abdominal pain.<br/>Neurological signs: dizziness, ataxia, somnolence, visual disturbances, hallucinations<br/>Moderate hepato-renal impairment, violet urine discoloration<br/>Duration: a few days</td><td>(Kraft et al., 1998; Villa et al., 2013)</td></tr><tr><td>Convulsive encephalopathy</td><td>Pleurocybella porrigens (Pers.: Fr.) Singer</td><td>Unknown mycotoxin<br/>Identified compounds: cyanide/thiocyanate ions, long-chain fatty acids, conjugated ketonic fatty acids with porrigonic acid, complex lectins, unstable amino acid.</td><td>Almost exclusively in patients with pre-existing renal failure.<br/>Delay: 1–31 days<br/>Tremor, dysarthria, muscle weakness, myoclonus<br/>Severe cases: coma, convulsions, status epilepticus, death from respiratory failure<br/>Duration: 1–2 weeks</td><td>(Kato et al., 2004; Gejyo et al., 2005; Akiyama et al., 2006; Amakura et al., 2006; Hasegawa et al., 2007; Wakimoto et al., 2011)</td></tr></tbody></table>
other European countries, and by the diversity of ecosystems favoring
mushroom growth. The aim of this study was to provide an overview of
their epidemiology in mainland France in recent years, in order to assess
their frequency, severity, and proportion relative to classical syndromes,
as well as to determine the appropriate public health response and the
preventive messages to be conveyed to the relevant healthcare
professionals.

## 2. Material and methods

A retrospective multicenter observational study was conducted on all
cases of mushroom ingestion-related poisoning recorded between 2015
and 2022 in mainland France. Data were extracted from the French
Poison Control Centers Information System (SICAP), which is populated
with cases reported to the eight French Poison Control Centers (PCC).
This national database has been approved by the French Data Protection
Authority (CNIL, No. 2020-131). Favorable approval for this study was
obtained from the local ethics committee (No. 2023-198).

### 2.1. Case selection

The included cases concerned all poisonings caused by mushrooms
known to be responsible for the "emerging syndromes," according to the
nomenclature in use at the time of intoxication: *Tricholoma equestre*,
*Tricholoma flavovirens*, *Tricholoma auratum*, *Russula subnigricans*, *Clitocybe acromelalga*, *Clitocybe amoenolens*, *Amanita proxima*, *Amanita smithiana*, *Amanita pseudoporphyria*, *Morchella* spp., *Lentinula edodes*, *Hapalopilus nidulans*, *Pleurocybella porrigens*. The implicated species were
identified from photographs, with identification performed by experts
from the Mycolite network (Bourgeois et al., 2017) whenever possible
independently of clinical data. When multiple mushroom species were
ingested, attribution was made to the most plausible culprit species
considering both mycological and clinical coherence. However, cases in
which a mycotoxic syndrome could be characterized were also included,
even in the absence of formal identification of the species involved.

### 2.2. Analyzed data

The analyzed data included socio-demographic characteristics (age,
sex, region, date of intoxication), the suspected species, possible con-
fusions between toxic and edible mushrooms, clinico-biological signs,
poisoning severity, outcome, causality assessment, and patient man-
agement (place and timing of care, treatments administered, length of
hospitalization). Case severity was assessed according to the Poisoning
Severity Score (PSS): PSS0 (no symptoms), PSS1 (minor), PSS2 (mod-
erate), PSS3 (severe), and PSS4 (fatal) (Persson et al., 1998). Causality
was assessed using the toxicovigilance causality method (Sinno-Tellier
et al., 2025). The toxicovigilance causality assessment method evaluates
the causal relationship between a suspected exposure and the observed
clinical manifestations. It relies on standardized criteria (chronology,
clinical features, biological plausibility, and analytical data). This
harmonized approach facilitates comparability across poison control
centers and strengthens the reliability of epidemiological signal detec-
tion. Cases are classified into five levels: not applicable (absence of
clinico-biological signs), not excluded, possible, probable, or very
probable.

Exclusion criteria were: null or not excluded causality, absence of
clinico-biological signs, exposure by a non-oral route, and intoxications
occurring outside mainland France.

Potential sources of bias included underreporting of cases (as not all
mushroom poisonings are notified to PCC), uncertainty in species
identification when based solely on photographs, and missing data
concerning mushroom quantities or cooking methods. These limitations
were mitigated through the use of a validated national database, stan-
dardized causality and severity assessments, and systematic expert re-
view for mycological attribution.

### 2.3. Statistics

Descriptive statistics were applied, with results expressed as means ± standard deviation (SD), medians with ranges, or proportions as appropriate. No inferential or multivariable analyses were performed, as the study was limited to descriptive epidemiology.

## 3. Results

Between January 1, 2015, and December 31, 2022, a total of 275
cases of poisoning related to the seven newly described mycotoxic
syndromes were reported by PCC, corresponding to an average of 34 ±
7.5 cases per year, or 1.7 % of the approximately 2000 mushroom
poisoning cases recorded annually.

The sex distribution was balanced, with a male-to-female ratio of
0.89. The mean age was 46.3 ± 18.0 years (range: 1–84; median: 45),
with a predominance of adolescents and adults (79 % of cases involved
individuals aged 13–64 years).

Geographic distribution was heterogeneous, with most cases occur-
ring in Occitanie (n = 50; 18.2 %), Auvergne-Rhône-Alpes (n = 46; 16.7
%), and Île-de-France (n = 44; 16 %). The specific distributions of the
emerging syndromes are shown in Fig. 1. Monthly distribution was also
uneven. A clear seasonal peak was observed in April, accounting for
42.2 % of cases (Fig. 2). This coincides with the spring fruiting of morels,
which represented the majority of syndromes during this period.

Among the seven emerging mycotoxic syndromes under investiga-
tion, only four were identified: neurotoxic syndrome from morels (n =
159; 57.8 %), flagellate dermatitis (n = 110; 40.0 %), *Amanita proxima*/
*smithiana* poisoning (n = 4; 1.5 %), and rhabdomyolysis (n = 2; 0.7 %).
Of all reported cases, 215 (78.2 %) were classified as low severity
(PSS1). Fifty-eight cases (21 %) were moderate (PSS2), linked to cere-
bellar syndrome (n = 56) and *Amanita proxima*/*smithiana* poisoning (n
= 2). Two cases (0.7 %), both associated with *Amanita proxima*/*smithi-
ana* poisoning, were classified as severe (PSS3).

### 3.1. Morel-related neurotoxic syndrome

Over the study period, 159 patients presented with a cerebellar
syndrome characterized by at least one neurological sign following
morel ingestion. The sex ratio was 0.94, with a mean age of 50.2 ± 17.7
years (range: 1–84; median: 50.3). Most cases occurred in April (n = 98;
61 %), mainly in Auvergne-Rhône-Alpes (n = 40; 25 %) and Occitanie
(n = 36; 22 %), corresponding to an average of 20 cases per year.

In most cases, the morels had been foraged (n = 107; 67 %); 15 % (n
= 24) involved store-bought mushrooms. Regarding preparation, morels
were insufficiently cooked in 43 % of cases (n = 69), adequately cooked
but consumed in large quantities in 42 % (n = 67), eaten repeatedly in
10 % (n = 15), and ingested raw in 5 % (n = 8).

Severity was low in 65 % of cases (PSS1, n = 103) and moderate in
35 % (PSS2, n = 56). The most frequent symptoms were dizziness (n =
109; 67 %), digestive disorders (n = 105; 66 %), and tremors (n = 85; 54
%), with mean onset times of 11.8 h, 10 h, and 12.5 h respectively, and
average durations of 17.4 h, 18 h, and 17.1 h. Other clinical signs
included ataxia (31 %, n = 48), headache (25 %, n = 41), and ocular
disturbances (18 %, n = 28), appearing on average 13 h post-ingestion
and lasting 15–18 h. Less frequent symptoms included hypotonia (6 %,
n = 9), dysarthria (3 %, n = 5), hallucinations (1 %, n = 2), and one
case of confusion (0.6 %, n = 1). Atypical manifestations, each reported
in a single patient (0.6 %), included tinnitus, high blood pressure, and
facial dyskinesia, with respective durations of 14 h, 10 h, and 24 h. All
occurred alongside typical features of neurotoxic morel syndrome.

A medical consultation occurred in 43 % of cases (n = 69), of which
59 % were with a general practitioner (n = 41) and 41 % in emergency
departments (n = 28). Only three patients required hospitalization.
<figure><img src="image_4.png" /><figcaption>**Fig. 1.** Geographic distribution of emerging mycotoxic syndromes (n = 274 cases). A, All emerging syndromes; B, Morel-related cerebellar syndrome; C, Flagellate dermatitis syndrome; D, Other syndromes reported in France.</figcaption></figure>

<figure><img src="image_5.png" /><figcaption>**Fig. 2.** Monthly distribution of cases of emerging syndromes (n = 274 cases).</figcaption></figure>

## 3.2. Flagellate dermatitis

Flagellate dermatitis syndrome was identified in 110 patients who presented with at least one cutaneous symptom after ingestion of *Lentinula edodes* (shiitake). The sex ratio was 0.82, and the mean age was 40.3 ± 16.5 years (range: 1–83; median: 37). Île-de-France was the most affected region, accounting for 27 % of cases (n = 30). On average, 14 cases were reported annually.

All patients exhibited at least one skin manifestation, including pruritus, erythema, or rash. The mean onset time of these symptoms ranged from 45.8 to 47.7 h (min = 6 h; max = 168 h). The mean duration of cutaneous signs ranged from 9.8 to 10.7 days. The most frequent sites were the trunk (55 %), the back (48 %), and the arms (46 %), although involvement of the legs and neck was also reported. Additionally, digestive symptoms were associated in 46 % of cases (n = 51), with a mean onset of 12 h and a shorter mean duration (0.8 days).

Among the 110 patients, 53 (48 %) consulted a physician, most often

a general practitioner (70 %, n = 37) or a dermatologist (15 %, n = 8). Sixty-four percent of patients received treatment (n = 71), mainly antihistamines (77 %, n = 55).

## 3.3. Amanita proxima/smithiana poisoning

Four patients (two women aged 51 and 56 years, and two men aged 55 and 67 years) were hospitalized following accidental ingestion of *Amanita proxima*, mistaken for *Agaricus arvensis*. All developed early digestive symptoms, with a mean onset of 10 h (range: 6–18 h) and lasting 3–10 days. Hospital stays ranged from 6 to 21 days (median: 13 days). Outcome was favorable in three cases (75 %) with complete recovery, while one patient (25 %) developed persistent ocular sequelae (significant visual field loss).

Acute kidney injury occurred in all cases (100 %), with a time to onset of 24–48 h and a duration ranging from 7 to 21 days. Peak serum creatinine levels varied from 190 to 1000 µmol/L, and two patients (50 %) required renal replacement therapy for 3 and 8 days, respectively. Renal function normalized within 9–35 days.

Moderate hepatocellular cytolysis was observed in two patients (50 %), with peak AST/ALT values ranging from 29 to 334 IU/L after 2–4 days, while the remaining two patients showed no hepatic involvement.

## 3.4. Rhabdomyolysis syndrome

Two cases of rhabdomyolysis syndrome were recorded during the 2015–2022 period, both occurring in Nouvelle-Aquitaine: one in a 65-year-old woman and the other in an 8-year-old child. In both cases, consumption of *Tricholoma equestre* was implicated, with symptom onset occurring after a delay of two to six days. Clinical signs were nonspecific, mainly characterized by myalgias. Symptoms lasted between 3 and 12 days, with spontaneous favorable outcomes in both cases. The severity of cases was considered low (PSS1), with no hospitalization or specific
treatment required. Consultations were limited to general practitioners. Only initial CPK values for the pediatric case were available; measured at 219 IU/L, they do not meet the usual biological criteria for rhabdomyolysis (>5 times the upper normal limit).

## 4. Discussion

Of the seven newly described mycotoxic syndromes reported in the literature, only four were observed in this study: the neurotoxic morel syndrome, flagellate dermatitis, *Amanita proxima*/*smithiana* poisoning and rhabdomyolysis.

The absence of acromelalgic, *Hapalopilus*-induced, and convulsive encephalopathy syndromes in our series may be explained by ecological and epidemiological factors. *Pleurocybella porrigens* does not occur in France, which likely accounts for the lack of cases of convulsive encephalopathy outside Japan. *Hapalopilus rutilans* is present in France but grows on decaying wood, and potential confusion with edible species is uncommon; the two French cases reported by (Villa et al., 2013) were linked to a misidentification with *Fistulina hepatica*, itself a species not particularly sought after by foragers. Finally, *Paralepistopsis amoenolens* is restricted to Mediterranean areas and therefore has a very limited geographical distribution in France (Moreau, 2001), which probably explains why no cases were recorded in our national series.

The very low incidence of rhabdomyolysis syndrome (two cases recorded) can probably be attributed to French regulatory measures, in particular the ban on the sale, possession, and import of *Tricholoma equestre* under Decree No. 2005–1184 of 2005 (Official Journal of the French Republic, September 19, 2005). Other European countries, such as Spain or Italy, have adopted similar measures (Peintner et al., 2013). Conversely, in some countries such as Portugal, Croatia, or Poland, *T. equestre* is still considered edible and authorized for sale. Some authors even dispute its toxicity (Rzymski and Klimaszyk, 2018). The absence of these mushrooms in commercial distribution, combined with demographic changes (aging populations), may have progressively led to a decline in their consumption habits. Updated mycology textbooks clearly mentioning their toxicity could also have reinforced this trend.

In our series, the low clinical severity could be explained by the absence of repeated large-scale mushroom consumption, whereas published cases generally report massive and iterative ingestions (sometimes up to 830 g/day for four weeks) (Bedry et al., 2001; Laubner and Mikulevičienė, 2016). Interpretation of the second recorded case was limited by substantial missing data, including creatine kinase values that did not meet conventional criteria for rhabdomyolysis.

*Amanita proxima*/*smithiana* poisoning was infrequent in our series. Clinical features were consistent with the usual classical presentation, characterized by moderate to severe acute renal failure within 24–48 h, with no progression to chronic renal impairment. However, in the Marseille series reported by de Haro et al., only 14 out of 53 patients developed renal impairment (oliguria or even anuria), whereas in our series, albeit limited to four patients, all presented with acute kidney injury (de Haro et al., 1998).

In addition, we report an unusual case of ocular sequelae characterized by severe visual field reduction, which has not been previously described in the literature for this syndrome. The only ocular complications reported to date following mushroom ingestion are endophthalmitis and macular deposits after *Amanita phalloides*, and convergence paralysis after *Amanita pantherina* ingestion (Gilad and Biger, 1986; Misiuk-Hojło and Magnowska-Woźniak, 1996).

Flagellate dermatitis and neurotoxic morel syndrome emerged as the most frequent entities in our series. This likely reflects the popularity of these mushrooms, which are both easily collected in the wild and widely available through commercial and online markets. The incidence of

flagellate dermatitis syndrome is increasing over the years. The mean onset time of cutaneous symptoms (48 h) and their distribution (trunk, arms, legs) are consistent with the most recent published series (Boels et al., 2014). No clear evolutionary pattern of skin lesions could be identified.

Most cases were linked to raw or insufficiently cooked shiitake consumption. However, 16 % of cases occurred despite proper cooking. Lentinan, the main shiitake polysaccharide, is suspected to play a role, yet its heat-lability does not fully explain persistent cases. The pathogenesis remains debated: while some studies suggest dose-dependent effects, others highlight idiosyncratic hypersensitivity linked to genetic predisposition and prior sensitization (Mak and Wakelin, 2006; Nguyen et al., 2017). Reports of vasodilation and hemorrhagic features (Wu et al., 2022) further complicate pathophysiological understanding, underlining the need for awareness of hypersensitivity reactions even with adequately cooked mushrooms (Netchiporouk et al., 2015; Stephany et al., 2016).

As with the previous syndrome, the neurotoxic syndrome associated with morels appears to be markedly increasing in case numbers since the series published by Saviuc in 2010 (Saviuc et al., 2010). The mean onset time of symptoms and their duration are comparable to published data (Pfab et al., 2008; Saviuc et al., 2010). The most frequent neurological signs remained dizziness, tremors, ataxia, and headaches (Saviuc et al., 2010). Atypical manifestations, never previously reported, were noted in three cases, alongside typical neurological features: tinnitus, arterial hypertension, and facial dyskinesia.

Undercooking and ingested quantity remain key factors in the development of symptomatology, although the responsible toxins have yet to be identified. Confusion with gyromitra consumption could not be entirely ruled out, but the absence of cytolysis, the transient nature of digestive symptoms, and the resolution of neurological disturbances within less than 24 h make this hypothesis unlikely, based on available data.

The apparent increase in neurotoxic and dermatological syndromes in our series likely reflects multiple converging factors: changing culinary practices with more frequent consumption of raw or insufficiently cooked mushrooms, wider availability of morels and shiitake in commercial and online markets, and a growing public enthusiasm for foraging. These evolving trends may explain why these two entities now predominate among the emerging mycotoxic syndromes recorded in France.

The results of this study confirm the importance of continued monitoring of mushroom poisonings, particularly emerging mycotoxic syndromes that may involve species previously considered edible, or the appearance of new clinical presentations of known mycotoxic syndromes. The article by Vodovar et al. on severe digestive poisonings following morel ingestion illustrates that mycology remains a constantly evolving field (Vodovar et al., 2024).

These findings also call for strengthened targeted prevention efforts, particularly regarding safe culinary practices, rigorous species identification and appropriate regulatory oversight. Preventive messages should emphasize that morels must always be thoroughly cooked (≥15–20 min) and never eaten raw, and that shiitake should only be consumed after sufficient heating to reduce the risk of flagellate dermatitis. The growing availability of mushrooms through online sales (shiitake, morels, etc.) and short supply chains further underlines the need for clear labelling and preparation guidance.

International experiences highlight the potential of prevention campaigns, although formal evaluation of their effectiveness remains limited. In China for instance, a structured prevention and treatment network was implemented in the Yunnan province. The system combined public education, improved diagnostic capacities, and a
hierarchical treatment system, was associated with a marked decrease in case fatality rates (Yao et al., 2023). Similarly, in Germany, targeted multilingual communication campaigns in refugee camps after fatal *Amanita phalloides* poisonings, illustrate the value of rapid awareness efforts adapted to specific populations.

Moreover, the evolution of practices and the regional distribution of mushroom consumption deserve particular attention. In Île-de-France, which is poorer in forested areas suitable for wild mushroom gathering, there is a high consumption of commercially available mushrooms, such as shiitake, through short supply chains and supermarkets. In contrast, in regions such as Eastern France or the Vosges, the collection of wild mushrooms (morels, chanterelles, porcini) remains a deeply rooted cultural and economic practice (Lang, 2015). These differences may explain certain regional variations observed in the distribution of syndromes. Similarly, the rarity of cases linked to *Tricholoma equestre* in northern France can be explained by the ecological preference of this species, which favors sandy and acidic forests of southern and Atlantic regions.

Finally, fungal population dynamics are evolving under the influence of climate change and range expansion. For example, *Chlorophyllum molybdites*, the main species responsible for poisoning among Europeans living in tropical regions (due to its resemblance to *Chlorophyllum rhacodes*), has recently been reported in areas such as Sicily, causing severe gastrointestinal disorders that may progress to shock in vulnerable individuals (Negrini et al., 2022). Similarly, certain North American amanita species, such as *Amanita smithiana*, have been observed in Europe and are responsible for an acute renal tubular syndrome distinct from the classical syndromes associated with European amanitas (Saviuc and Danel, 2006).

Beyond mushrooms, other emerging natural toxic syndromes raise similar challenges for prevention and public awareness. In Europe, cases of tetrodotoxin poisoning from pufferfish and shellfish in the Mediterranean have been reported (Gouel et al., 2022), as well as intoxications caused by grayanotoxins in so-called “mad honey,” traditionally described in Turkey but now occasionally seen in Europe (Aryal, 2025). In parallel, recent studies on foodborne mycotoxins (Abdel-Daim et al., 2021; Menezes Filho et al., 2022) also highlight the broader public health implications of natural toxin exposure, reinforcing the need for sustained toxicovigilance and preventive communication.

This study presents several limitations inherent to its retrospective design. Data were extracted from poison control center records, which depend on the accuracy and completeness of information provided during emergency calls. As a result, important variables such as the exact quantity of mushrooms consumed, the number of meals, or the precise cooking methods were often missing. These factors are particularly relevant, since both dose and preparation strongly influence the occurrence and severity of certain syndromes, as highlighted for *Tricholoma equestre* or morels.

Species identification, although supported by the Mycolist expert network, sometimes remained uncertain when only poor-quality photographs were available (Bourgeois et al., 2017). The continuous evolution of fungal nomenclature further complicates the real-time attribution of species names. Advances in molecular phylogeny have led to frequent changes in nomenclature, such as the reclassification of *Clitocybe amoenolens* and *Clitocybe acromelalga* into the genus *Paralip stipopsis*. These shifts complicate comparisons over time and across regions, since older reports may use obsolete names or include heterogeneous species groups.

An underreporting bias must also be considered: mild cases are unlikely to be reported to poison control centers, and some severe poisonings may bypass the system if patients are admitted directly to hospital. Variations in coding practices across centers can introduce

heterogeneity in the classification of symptoms, severity, and outcomes within the SICAP database. Follow-up information was frequently incomplete, leading to uncertainty about the true rate of sequelae.

These factors must be considered when interpreting the results and highlight the importance of prospective studies incorporating standardized data collection, systematic mycological expertise and active clinical follow-up to capture long-term outcomes.

## 5. Conclusion

These new syndromes account for less than 2 % of mushroom poisoning cases in France, but their frequency is steadily increasing. For healthcare professionals, these data provide valuable input for preventive messages. Our findings confirm the predominance of cerebellar syndromes related to morels and flagellate dermatitis due to shiitake, while also documenting atypical neurological features and rare ocular sequelae. These findings underline the importance of continuous surveillance through the poison control network and the need to raise clinician awareness of syndromes that may still be under-recognized.

From a public health perspective, the results support the reinforcement of information campaigns emphasizing correct cooking methods for morels and shiitake, as well as the dangers of confusing *Amanita proxima* or *Tricholoma equestre* with edible species. Foragers should be encouraged to seek expert identification when in doubt, and consumers should be reminded that even “traditionally edible” species may cause unexpected toxicity.

The discovery of new mycotoxic syndromes and the evolving ability of mushrooms underline the importance of continuous education for clinicians, professional societies, and expert mycologists, as well as the regular updating of reference literature.

### CRediT authorship contribution statement

**Chloé Bruneau:** Conceptualization, Methodology, Writing – original draft, Supervision. **Manon Poilane:** Investigation, Data curation, Formal analysis, Writing – original draft. **Jérémy Lecot:** Visualization, Writing – review & editing. **Anne Landreau:** Conceptualization, Writing – review & editing, Supervision. **Gaël Le Roux:** Writing – original draft, Supervision.

### Ethical statement

This study was based on anonymized data collected by French Poison Control Centers during routine medical consultations. Patients are systematically informed during the telephone call that their case may be used for research purposes. According to national regulations, no individual consent is required for such retrospective analyses. The study was approved by the local ethics committee (Ref. 2023–198) and authorized by the French Data Protection Authority (CNIL, Ref. 2020–131).

### Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

### Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
# Data availability

Data will be made available on request.

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