Overview

Fungal infections of the hand (tinea manuum) and nails (onychomycosis) are common diseases. Despite this, they are overlooked as cosmetic issues when their effect can be skin-deep. Not only do they cause physical impairment, but they also cause emotional, financial, and social harm. This article aims to be an eye-opener on the importance of their diagnosis, treatment, and prevention.

Epidemiology 

Approximately 3%(1.7M people) of the adult population in the UK suffers from onychomycosis.¹ A figure that can only grow due to the increasing life expectancy, number of sporting activities, and changing environmental conditions. Diabetics are almost three times more likely to develop onychomycosis than non-diabetics.² The elderly and the immunocompromised population are also among the vulnerable population. Tinea manuum is less common as compared with tinea pedis and is usually associated with two feet, one hand syndrome - the hand used to scratch the infected feet gets infected. For example, predisposing factors for onychomycosis include diabetes mellitus, older age, hyperhidrosis, onychogryphosis, nail trauma, poor peripheral circulation, and immunosuppression.¹²

Causative organisms

Dermatophytes are the main organisms implicated in the causation of tinea manuum and onychomycosis. The species that most often cause onychomycosis in North America and parts of Europe are T. rubrum, T. mentagrophytes, and Epidermophyton floccosum; the first two species are much more often implicated than E. floccosum.⁴ Other causative organisms include Candida albicans and non-dermatophytic moulds. It is important to identify the organism as it determines the treatment choice.  

Symptoms

Classification of onychomycosis

• Distal subungual onychomycosis: The most common type. It involves the invasion of the flesh beneath the nail (nail bed), the underside of the nail plate (the nail itself), and the beginning of the most distal aspect of the nail bed (hyponychium). It then migrates proximally through the growth centre of the nail (nail matrix). This causes hyperkeratosis of the subungual nail, onycholysis, and predisposition to secondary bacterial infections
• Proximal subungual onychomycosis; Relatively uncommon. Occurs when the organism penetrates the cuticle into the proximal nail hold, invades the newly formed nail plate then progresses distally. This leads to subungual hyperkeratosis, onycholysis, leukonychia, and destruction of the proximal nail plate. n, it is common in AIDS patients and is considered an early clinical marker of HIV infection⁵
• Superficial White Onychomycosis; Less common than distal subungual onychomycosis, occurring when certain fungi invade the superficial layers of the nail plate directly. It can be recognised by the presence of well-delineated opaque “white islands” on the external nail plate, which coalesce and spread as the disease progresses. At this point, the nail becomes rough, soft, and crumbly⁶
• Candida Infections of the Nail: Caused by Candida albicans.⁷ The organism invades the entire nail plate. Candida spp. may cause other syndromes, including onycholysis and paronychia. Invasion by Candida spp., unlike dermatophytic invasion, penetrates the nail plate only secondarily after it has attacked the soft tissue around the nail.⁶ After infection of the nail matrix occurs, transverse depressions (Beau’s lines) may appear in the nail plate, which becomes convex, irregular, rough, and, ultimately, dystrophic. Patients with chronic mucocutaneous candidiasis are at risk for the second type of Candida onychomycosis, called Candida granuloma, which accounts for fewer than 1% of onychomycosis cases^{6, 13, 8}
• Total Dystrophic Onychomycosis: The end result of any of the four main patterns of onychomycosis. The entire nail unit becomes thick and dystrophic⁸
• Endonyx onychomycosis; The fungus penetrates the distal nail keratin of the nail plate, where it forms milky white patches without subungual hyperkeratosis or onycholysis
• Mixed pattern onychomycosis; Different patterns of nail plate infection may be seen in the same individual. The most common combinations include Proximal subungual onychomycosis with Superficial White Onychomycosis and Distal subungual onychomycosis with Superficial White Onychomycosis⁹

Tinea manuum manifests as crusted, itchy, round, scaly lesions on the hand. They can appear as ringworms on the dorsal aspect of the hand and be hyperkeratotic with a fine white scale, emphasising the normal lines of the hand on the palmar aspect. 

Patients may fear that they will transmit their infection to family members, friends, or coworkers, fears that can lead to diminished self-esteem and the avoidance of close relationships.¹³

Finally, onychomycosis can compel workers to take periodic sick leave, a problem even for treated patients if therapy is ineffective and/or long-lasting.¹³

Onychomycosis in immunocompromised patients, such as those infected with human immunodeficiency virus (HIV), can pose a more serious health problem.¹³ Not only does the difficult-to-treat infection serve as a constant reminder to the patient of his or her own deteriorated condition, but the possibility exists of transfer of a very high titer of fungal pathogens to another person.¹³

Differential diagnosis

Common conditions that can be confused with onychomycosis are psoriasis (the most common such disorder), lichen planus, bacterial infections, contact dermatitis, traumatic onychodystrophies, pachyonychia congenita, nail bed tumours, yellow-nail syndrome (rare), and idiopathic onycholysis.¹⁷

A diagnosis of psoriasis is supported by the presence of fine pitting on the nail surface, the small salmon-colored “oil drop” sign of onycholysis that is not seen in onychomycosis, and fingernail involvement of both hands.¹⁰

Tinea manuum may mimic eczema, contact dermatitis, palmar psoriasis or dryness of the hand. 

Specimen collection

Proper collection of specimens is important for accurate results. 

Diagnosis

• KOH scrappings; Observation of fungal hyphae keenly is key as one can also observe the hyphae to differentiate between different causative organisms.  The test serves only as a screening test for the presence or absence of fungi but cannot differentiate among the pathogens.  Be aware of the possibility of false-negative results, which occur at a rate of approximately 5 to 15%^{11, 12}
• Culture: The gold standard and the only investigation that can detect the specific causative organism
• Molecular diagnostics are used to detect fungal load and mixed-organism disease
• Histopathology;  Nail biopsy is also helpful in differentiating nonmycotic onychodystrophy caused by psoriasis and lichen planus, but can cause permanent nail dystrophy¹⁸

Treatment and management

Treatment heavily relies on the identification of the organism and the consideration of comorbidities, age, and other patient factors. Medication has long evolved from those requiring long-duration (like griseofulvin) and having adverse side effects to more tolerable and shorter-duration medications. The adverse effects, primarily due to the CYP450 pathway interference of the medication, decreased as drugs less dependent on the pathway were developed. Older drugs include griseofulvin, ketoconazole and fluconazole, while newer drugs include itraconazole and terbinafine. Oral itraconazole and oral terbinafine are clearly superior to griseofulvin in treating onychomycosis, with cure rates in the range of 70% generally reported.^14,15 Terbinafine is not dependent on the CYP450 pathway and thus has fewer drug interactions. Because itraconazole inhibits the cytochrome P-450 enzyme system, itraconazole should not be taken with terfenadine, astemizole, simvastatin, lovastatin, midazolam, triazolam, or cisapride.¹⁶

Organism-specific treatment

• Dermatophyte; Terbinafine and Itraconazole (continuous vs pulsing)
• Non-dermatophytic moulds; Itraconazole
• Candida; Fluconazole or Itraconazole

Population-specific treatment 

• Children: Pulse itraconazole therapy (5 mg kg−1 per day for 1 week every month) is recommended for 2 months for fingernail infection and 3 months for toenail infection. Fluconazole is recommended at 3–6 mg kg−1 once weekly for 12–16 weeks for fingernail infection and 18–26 weeks for toenail infection. Daily terbinafine is recommended for 6 weeks for fingernail and 12 weeks for toenail infection at 62·5 mg per day if weight is < 20 kg, 125 mg per day for 20–40 kg weight, and 250 mg per day if weight exceeds 40 kg. Griseofulvin is the only licensed systemic antifungal for children; however, itraconazole and terbinafine are generally accepted.
• Pregnancy; None approved
• Diabetes Mellitus; Terbinafine due to fewer drug interactions
• Elderly

Dosages

Itraconazole

200 mg per day for 12 weeks continuously

400 mg per day for 1 week per month. Two pulses are recommended for fingernail onychomycosis and three pulses for toenail onychomycosis.

Terbinafine

(500 mg per day for 1 week per month for 3 months

250 mg per day for 3 months)

Fluconazole

450 mg per week for 3 months in fingernail infections, and for at least 6 months in toenail infections

Other drugs

Echinocandins

Second‐generation triazoles (new triazoles) eg Voriconazole

Combination therapy 

1. Topical nail lacquers
2. Surgical

Treatment failure

The reasons for the 20% failure rate include inaccurate diagnosis, misidentification of the pathogen, and the presence of a second disorder, such as psoriasis.¹⁹ In some cases, characteristics of the nails, such as slow growth or excessive thickness, make treatment difficult. The presence of a high fungal inoculum and/or drug-resistant microorganisms is particularly challenging. Host-related factors such as a compromised immune system (typically seen in individuals infected with HIV), diabetes mellitus, or peripheral vascular disease may also impede success.¹⁹ Unfortunately, some people seem to have a genetic predisposition to fungal infections, and these people may experience relapses despite careful care and effective therapy.¹⁹

Follow-up post-treatment

It is important to follow up with the patients while on treatment. A complete blood count and liver function should be considered as part of follow-up. 

Foot hygiene

Patient education on foot hygiene should be paramount. 

The patient must be informed of the risk of relapse and the chances of failure of treatment for a realistic approach to the medication. 

Summary

Tinea manuum and onychomycosis are common conditions affecting the population emotionally, financially, and physically. Research has come a long way to provide better treatment options, but still has a long way to effect appropriate care for these patients. A proper history to pick out risk factors,  physical examination, and investigation will go a long way in helping the population affected.