Introduction

The word paronychia comes from the root para, (around) and onukh (nail) and literally means next to the nail [1]. Inflammation of the tissues surrounding the nail plate of the fingers or toes is commonly referred to as paronychia, and less commonly as perionyxis. Paronychia may be acute or chronic and may be related to multiple local or systemic conditions, drugs, as well as bacterial, viral, parasitic, or fungal infections. Classification and treatment is based on the main cause [2].

Chronic paronychia can be defined as inflammation of the proximal and or lateral fold of the nail for more than 6 weeks [3]. It is a frequent dermatological condition, especially in the nails of the hands of adult women, usually of the hand and dominant fingers. The most common sites are the right hand and thumb, index, and middle fingers (Fig. 1a). Some of the major predisposing factors for paronychia are trauma and constant moisture, local irritants, finger sucking, housework, washing clothes or dishes, cooking, and manicure treatments. The loss of the cuticle or the periungual folds may allow the entry and infection of fungal microorganisms and perpetuate inflammation of the soft tissues [4,5,6].

Fig. 1
figure 1

a Chronic Paronychia. b Candida Paronychia. c Paronychia in lymphangitic sporotrichosis. d Paronychia in primary cutaneous coccidioidomycosis. e Psoriatic paronychya. f Candida sp.

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The first report of mycotic paronychia associated with yeasts is that of Kingery and Thienes in 1925, in fruit canners [7]. Fungal paronychia has been associated more frequently with yeast infection by Candida and less common with other yeasts or filamentous fungi [8,9,10,11].

Fungal Paronychia

In Candida paronychia, the onset is chronic paronychia with loss of the cutaneous barrier, absence of the cuticle, and separation of proximal and lateral periungual folds. Constant exposure to liquids, sugars, or irritants produces a humid environment that favors colonization and infection by Candida spp. [12]. At the beginning, there is erythema and edema of the proximal or lateral nail folds, followed by its separation from the eponychium (Fig. 1b); transverse grooves, Beau’s lines, and subsequent infection of the nail matrix that finalizes with onychodystrophy are observed in the true Candida onychomycosis, caused by infection of the nail plate [13, 14]. In addition to patients with pure onychomycosis, Candida spp. may be encountered in patients that present with isolated paronychia and onycholysis [8, 9]. Thus, secondary infection of the nail apparatus by the yeast in chronic paronychia with nail dystrophy can be one of the invasion routes of the nail plate and finally determine its classification as Candida onychomycosis [14, 15].

The denomination of fungal paronychia by Candida may be controversial, with certain exceptions versus chronic mucocutaneous candidiasis, considering that yeast is not a primary pathogen, but only a colonizer in a susceptible field, whereby restoring the periungual skin barrier, the fungus could be eliminated [16,17,18]. Thus, Candida is a secondary colonizer, which in many cases of chronic paronychia can cause episodes of acute painful inflammation [19].

C. albicans, C. parapsilosis, C. tropicalis, and C. krusei have been isolated in paronychia of the fingernails [20]. C. albicans, C. parapsilosis, and C. guillermondii, on the other hand, are found on fingernail onychomycosis [21, 22]. These species have potential pathogenicity to produce fungemia [23].

Candida albicans can cause superficial and systemic infections due to the development of diverse and complex virulence mechanisms such as polymorphism, phenotypic changes, and expression of adhesion molecules and invasion of cell surfaces, tigmotrophism, biofilm formation, and secretion of hydrolytic enzymes [24, 25]. Some of these, such as adhesion, filamentation, and production of extracellular enzymes have been linked to Candida onychomycosis [26]. In cutaneous candidiasis and vaginal infections, a compromise of the mononuclear and neutrophilic phagocytic system has been observed [25].

Candida paronychia may be seen in patients with chronic mucocutaneous candidiasis as primary immunodeficiency carriers. These patients present an altered cellular immune response against C. albicans [27]. In a study in subjects with autosomal dominant CMC, a defect in the Th1 and Th17 response was determined by mutations in the signal transduction and of transcription 1 activation [28].

On the other hand, the antigenic role of Candida has been suggested in patients with chronic paronychia, not only as secondary colonizer; these patients may exhibit a hypersensitivity response to Candida antigen exposure [6].

Trichosporon spp. has been considered as a causative agent of paronychia. In addition to cases of white piedra and superficial skin infections, Trichosporon cutaneum, T. asahii, and T. mucoides have been isolated from the nail apparatus of patients with hiponyxis, perionyxis, or onychomycosis [29,30,31,32]. Trichosporon infections have been categorized as reemerging. A review of systemic trichosporonosis shows this disorder in oncological, hematological, and immunocomprimised patients, newborn infants with fungemia, or those with lung and skin infections. Main etiological agent’s were T. asahii, followed by T. inkin [33].

Paronychia Due to Dermatophytes

Dermatophytes are the main fungal causative agents of dermatomycosis. They can cause primary infection of the skin, hair, or nails; their virulence factors are the ability to adhere to the keratinized epithelium and the production of keratolytic enzymes such as hydrolase and dioxygenase cystein [34].

Although it is extremely rare, dermatophyte paronychia may develop secondary to proximal subungual onychomycosis (PSO) due to infection of the nail plate and posterior invasion of the nail folds and cuticle [9, 35]. These cases may occur with paronychia and chronic inflammation, such as reported with pseudo acropachya by Trichophyton rubrum, like cases associated with chronic mucocutaneous candidosis [36]. Dermatological infection of the nail can be mixed, combined with non-dermatophyte fungal infections, and can produce paronychia and onychomycosis [37].

Paronychia by Non-dermatophyte Fungus

Non-dermatophytic hyalohyphomycosis is generally seen in disseminated form in hematological and immunocompromised patients [38]. In these cases, non-dermatophyte infections of the skin are frequent and up to 60% are produced by Fusarium [39]. Fusarium stands out as an important emerging opportunistic fungus that can produce infections on the skin and nails [40•].

Filamentous fungi are commonly found in the environment as saprophytes of soil or plants. Once inside the infected tissues, they exist in the intercellular cement substance. Except for Neoscytalidium sp., they lack keratolytic affinity and secondarily invade damaged keratinized tissue [15, 41]. The following non-dermatophyte molds have been frequently isolated in onychomycosis: Scopulariopsis brevicaulis, Fusarium spp., Aspergillus spp., Neoscytalidium dimidiatum (formerly Scytalidium dimidiatum), and Acremonium spp. [41, 42]. These same molds, like Fusarium spp., Aspergillus spp., and Scopulariopsis sp. can cause subungual proximal onychomycosis associated with paronychia with signs of inflammation, erythema, and edema of the folds of the nail, including the presence of pus [9, 43,44,45].

Paronychia and onychomycosis by F. oxysporum have been found in nails of the hands of immunocompetent women [46, 47]. In immunocompromised cases of paronychia, Fusarium sp., F. oxysporum, and F. solani have been isolated, including cases mimic Candida paronychia, these cases of paronychia have been the onset of disseminated fusariosis [48,49,50]. Fusarium can produce paronychia without invasion of the nail plate, subacute paronychia, leukonychia, and proximal white onychomycosis in immunocompromised patients. Fusarium and Neoscytalidium, as well as Candida, can lead to subungual proximal onychomycosis secondary to paronychia [44].

Aspergillus spp. can produce paronychia and leukonychia, proximal leukonychia or total onychomycosis (TO), and paronychia with PSO or TO [51]. Aspergillus niger can cause proximal subungual onychomycosis with paronychia and black pigmentation of the lunula [44].

Exceptional Fungal Paronychia

Parasite and fungal agents mainly causing subcutaneous or systemic infections, such as Leishmania spp., Sporothrix spp., and even Coccidioides sp., could be cause of infection because of the rupture of the integrity of the periungual folds. Direct trauma and inoculation of these microorganisms in the periungual tissues or the adjacent skin can cause paronychia of one finger or toe; there result mainly in cases of exceptional fungal paronychia in endemic areas (Fig. 1c, d) [44, 52,53,53].

Diagnosis

The primary diagnostic objective is to eliminate other possible common causes of chronic perionyxis such as atopic dermatitis, psoriasis, lichen planus, traumatic injury, and other rare causes of paronychia like retronychia (Fig. 1e) [6, 12, 54, 55]. Patients who are immunosuppressed or have a neoplasia, in addition to being able to have paronychia of infectious origin, may present paronychia, onycholysis, and secondary onychodystrophy due to toxicity to capecitabine and taxanes, or cetuximab as a direct consequence of inhibition of keratinocytes of the nail matrix [56,58,58].

It is necessary to perform the diagnosis of paronychia of mycotic origin as accurately as possible, to determine whether it is a pure onychomycosis without nail fold involvement, or both conditions are present at the same time [8].

The study of yeasts can be performed by means of direct microscopic examination of the scales obtained from the periungual folds and observation of abundant yeasts or pseudo hyphae and hyphae, culture in the medium of simple Sabouraud dextrose agar and with antibiotics and CHROMagar Candida® for the isolation and identification of Candida and Trichosporon spp. (Fig. 1f) [21]. Histopathologic analysis was previously employed [8] as part of the diagnostic investigation of Candida infections of the nail apparatus, including paronychia; currently, the biopsy resource is controversial or limited to scientific or academic studies.

For the identification of dermatophytes in onychomycosis, traditional laboratory studies based on culture and isolation of the fungus can be carried out and in the microscopic study with potassium hydroxide (KOH) and chlorazol black or calcofluor white. It is necessary to obtain a sufficient sample of the periungual skin folds, and in the case of cutaneous and ungual affection, to study separately both sites for their adequate diagnosis. It is also important to determine whether the infection is caused by one or more than one fungal agent. Histopathological study with Schiff periodic acid staining (PAS) has been shown to be more sensitive than direct microscopic examination and culture in onychomycosis, but it is necessary to be evaluated in paronychia and because it is an invasive procedure of the nail apparatus, it is not routinely employed. In the diagnosis of Candida spp., Trichosporon and dermatophytes, new molecular diagnostic techniques can be used. For detection and identification of dermatophyte, real-time PCR can be performed in less than 2 days [15, 59].

In the diagnosis of paronychia due to non-dermatophyte molds, besides the history and the clinical signs, the diagnostic criteria in onychomycosis for non-dermatophyte molds suggested by Gupta et al. may be used and applied to the affected pterygium: microscopic identification of the fungus in nail fold scraping, isolation of the fungus in culture, repeated isolation of the same fungus in cultures, amount of inoculum, no isolation of dermatophytes in culture, and histopathological criteria [43].

Guidelines in the diagnosis and treatment of hyalohyphomycetes suggest that the search for hyaline molds is based on direct microscopic examination and cultures on medium without cycloheximide, and histopathology may be essential in the investigation. Identification of mold species includes the use of electronic microscopic and molecular identification methods that are important to guide diagnosis and treatment [38, 51, 60].

Treatment

The treatment of superficial mycoses, including mycotic paronychia, is based on the involved fungus, and treatment may include novel or well-known topical or oral antifungals. Amorolfine is a fungicidal agent that targets C. albicans and T. mentagrophytes. Ciclopirox is broad-spectrum, acting on Candida spp., T. rubrum, and S. brevicaulis. Itraconazole has an effect against yeasts, dermatophytes, and non-dermatophytes. Fluconazole has some activity on Candida spp. and dermatophytes. Terbinafine is a fungicidal drug against dermatophytes with activity against S. brevicaulis and Neoscytalidium spp. [15, 43, 61]. Voriconazole has a high activity and broader action spectrum against dermatophytes and Candida spp., Scopulariopsis, Neoscytalidium, and Fusarium. Posaconazole is also broad-spectrum, with activity against yeasts, dermatophytes, and molds. Albaconazole shows intense activity against Candida spp. and Aspergillus spp. [15, 35, 38].

New topical fungal antigens have recently emerged for use in onychomycosis. Efinaconazole is a broad-spectrum triazole. It acts in vitro against dermatophytes, non-dermatophytes, and yeasts. Tavaborole belongs to a new class of antimycotics, active in vitro against dermatophytes, C. albicans, A. fumigatus, and F. solani [62, 63].

Treatment of chronic paronychia and Candida infection should include protective measures to avoid contact with allergens and irritants, excessive humid environment, as well as manicure and pedicure [5, 35]. The traditional treatment of paronychia by Candida has long consisted of the use of topical azoles and polyenes antimycotics [12, 64]. Clinical studies related to fungal paronychia and its treatment are very scarce. Pharmacological therapy based on topical steroids and topical antimycotics such as cyclopirox or both have been used in chronic paronychia associated with Candida to reduce the inflammatory process and restore the skin barrier. The reappearance of an adherent cuticle allows healing [5, 16, 65].

Topical treatment with several drugs combined in a single cream has been suggested as prevention and treatment of chronic paronychia, including association with infection with Candida spp. The formulation is based on the antimycotics octopirox and climbazole, as well as a polymer as a protective barrier and an anti-inflammatory [65]. Natural products have demonstrated some antifungal activity against biofilms of Candida spp. Among them are peptide (18-amino acid cationic ApoEdpL-W), Peptide (Trapanatans), Romanian plant extracts, Coriandrum sativum L., cinnamon oil, usnic acid, and some of these compounds could be investigated for their efficacy and safety in Candida paronychia [25].

Itraconazole and terbinafine are the oral antifungal agents approved for the treatment of onychomycosis by dermatophytes and can be used in paronychia associated with dermatophytic onychomycosis [62]. Itraconazole and terbinafine are also the most effective drugs for non-dermatophyte molds that are most frequently involved in onychomycosis and paronychia [15, 43]. Terbinafine has been used in onychomycosis and paronychia by Aspergillus spp. with initial decrease of pain by paronychia and good final results of onychomycosis [66].

Isolated cases of paronychia have been reported for non-dermatophyte molds treated successfully with topical antifungal drugs such as 5% occlusive amorolfine against F. solani refractory to topical ketoconazole and oral terbinafine, [49] as well as the use of clotrimazole in paronychia by Curvularia lunata [67].

Comments

In the paronychia syndrome, diverse species of fungi are related to the inflammation of the periungual tissues; predisposing factors, clinical, and laboratory data are necessary to determine their participation in the disease.

Candida spp. in the nail apparatus may be considered commensal organisms, primary pathogens, or mainly opportunistic organisms. Candida paronychia is a frequent condition and may precede proximal subungual onychomycosis by Candida; studies are needed to determine the pathogenic systems of Candida that could participate in this special condition of the nail unit, most of the reports are directed to onychomycosis.

Dermatophytes are the main causative agents of dermatomycosis, they can invade the keratinized epithelium of the proximal and lateral folds of the nail, but infrequently produce inflammation of the nail folds. Certain non-dermatophyte mold species may act on previously injured skin or nails and produce paronychia; these fungi may be secondary, opportunistic pathogens in immunocompromised subjects, or even behave as primary pathogens in healthy individuals.