## 3 Results
### Study Characteristics and Qualitative Synthesis
& \\  & & & Numerous & \\  & & & \"metal-like particles\", & \\  & & & inclusions within & \\  & & & macrophages, & \\  & & & perivascular region & \\  & & & **Time to onset**: MD & \\ \hline  & & & & **Definitive diagnosis:** \\  & & & & MD \\ Cases n.70 & & & & **Diagnostic procedure(s):** \\ N/D with Ti allergy & & & **features**: & Cutaneous and \\  & & & & epicutaneous test for Ti: \\  & &Findings from 555 cases, accounting for 16.9% of the overall study population, diagnosed with lesions resembling or ascribable to peri-implant mucositis and peri-implantitis, peri-implant reactive lesions, and orofacial, periodontal, and peri-implant hypersensitivity reactions potentially due to Titanium (alloy) and other metal nanoparticles released from dental implants and implant-supported restorations, were obtained. Cases history of \begin{table}
\begin{tabular}{c c c c c c} \hline \hline \multirow{2}{*}{**Source**} & \multirow{2}{*}{**Studies and Population**} & \multirow{2}{*}{**Cases**} & \multicolumn{2}{c}{**Dental Implants**} & \multirow{2}{*}{\
\begin{tabular}{c} **Reported Lesions** \\ **and** \\ **Hypersensitivity** \\ **Reactions** \\ \end{tabular} } & \multirow{2}{*}{
\begin{tabular}{c} **Diagnosis, Therapy, and** \\ **Progression Evidence of** \\ **Titanium Allergy** \\ \end{tabular} } \\  & & & & & \\ \hline \hline \end{tabular}
\end{table} 
Table 1: _Cont._allergies was reported in 19 cases [36]; allergens were not specified. Cases comorbidities described in two cases [35] were psoriasis and seborrheic eczema, and related therapies were not detailed. Data on 31 dental implants [34; 36; 37] were currently retrieved. Dental implants' position was specified for two fixtures placed in maxillary [36] and eleven in mandibular [36] dental arches. Implant-supported restorations were never specified. Dental implant survival was noticed in five cases [34; 36] in a time range between 1 week and 2 years. The clinical appearance of the reported lesions was recorded in 29 (5.22%) cases, describing: (58.64%, n = 16) macroscopic features likely resembling peri-implant mucositis and peri-implantitis with or without implant loss (n = 2),defined as \"clinical symptoms and/or implant loss\" [36] and (3.44%, n = 1) swelling, erythema, bleeding of the peri-implant mucosa and a deep probing depth [36]; (6.89%, n = 2) exophytic lesions of the peri-implant mucosa, identified as Pyogenic granuloma and Peripheral giant cell granuloma [36], (6.89%, n = 2) gingival overgrowth (defined as \"gingival hyperplasia\") [34], and (3.44%, n = 1) a not better-defined peri-implant chronic inflammatory response with fibrosis [34], likely identifiable as reactive lesions of the peri-implant mucosa (17.24%, n = 5); (17.24%, n = 5) facial eczema and/or unspecified local reactions [36], (3.44%, n = 1) swelling and hyperemia [34], and (3.44%, n = 1) orofacial erythema, swelling and lip crease [36], ascribable to orofacial, periodontal and peri-implant hypersensitivity reactions (24.12%, n = 7) (Figure 2). Lesions potentially due to Titanium (alloy) and other metal nanoparticles released from dental implants and implant-supported restorations  
The imaging features were illustrated in five cases [36], with images suggestive of peri-implant bone loss in two cases and showing an irregular radiolucent area in one case; no bone loss was observed in the remaining two cases [36]. Microscopic features were depicted in four cases, describing an inflammatory infiltrate and/or \"metal-like\" particle inclusions within macrophages in three cases [36]; no histopathological alterations were found in one case [36]. The time to lesion onset was delineated in one case diagnosed with facial eczema, occurring two years after implant placement [36]. Definitive diagnoses, reported in three cases, were (n = 1) type IV hypersensitivity (\"orofacial erythema, swelling and lip crease\") [36], (n = 1) pyogenic granuloma [36], and (n = 1) peripheral giant cell granuloma [36].