Erythrasma

Erythrasma is a chronic superficial infection of the intertriginous areas of the skin. The incriminated organism is Corynebacterium minutissimum, which usually is present as a normal human skin inhabitant. In 1996, Corynebacterium afermentans was reported in one case.[1]

In a more recent study, two colonies of Corynebacterium aurimucosum and Microbacterium oxydans were isolated from the interdigital web of the left foot in a 78-year-old woman indicating that other species of microorganisms may be responsible for this condition.[2]

Corynebacteria invade the upper third of the stratum corneum; under favorable conditions such as heat and humidity, these organisms proliferate. The stratum corneum is thickened. The organisms that cause erythrasma are seen in the intercellular spaces as well as within cells, dissolving keratin fibrils. The coral-red fluorescence of scales seen under Wood light is secondary to the production of porphyrin by these diphtheroids.

C minutissimum, a member of the normal skin flora, is the causative agent of erythrasma. The bacterium is a lipophilic, gram-positive, non–spore-forming, aerobic, and catalase-positive diphtheroid. C minutissimum ferments glucose, dextrose, sucrose, maltose, and mannitol.

Whole-genome sequencing of C minutissimum has been reported to better understand the multiantibiotic resistance that has been observed and its virulence factors specifically in immunocompromised hosts. The will make it possible to identify the genes contributing to antibiotic resistance and to better design treatment options in these special cases.[3]

Predisposing factors for erythrasma include the following:

• Excessive sweating/hyperhidrosis

• Delicate cutaneous barrier

• Obesity

• Diabetes mellitus

• Warm climate

• Poor hygiene

• Advanced age

• Other immunocompromised states

Frequency

The incidence of erythrasma is reported to be around 4%. This infection is observed all over the world; the widespread form is found more frequently in the subtropical and tropical areas than in other parts of the world.[4] .The infection occurs less often in children and tends to be more prevalent among college students in dormitories, soldiers in barracks, and senior adults in nursing facilities. Erythrasma incidence may increase with age.

In a study conducted in Turkey, the rate of erythrasma was found to be 46.7% among 122 patients with interdigital foot lesions.[5]

In a cross-sectional study of 80 patients with confirmed superficial cutaneous intertriginous infections in Tehran, Iran, erythrasma was the second most common infection after dermatophytosis[6] ; it accounted for 35% of the cases. The toe-web spaces were the most common sites, followed by the groin and axillary vaults.

The occurrence of erythrasma on the palm of one patient has been reported and appears to be unique and rare.[7]

Race

The incidence of erythrasma is higher in black patients.

Sex

Both sexes are equally affected by erythrasma; however, the crural form of erythrasma is more common in men. A 2008 study found that interdigital erythrasma was more common in women (83% of 24 patients).[8]

A more recent study conducted in India confirmed the absence of sex predilection and observed that it was more commonly detected in patients with a body mass index of greater than 23 kg/m2 (62.5%) and in those with diabetes (50%).[9]

Age

The incidence of erythrasma increases with age, but no age group is immune to the disease. The youngest patient reported to have erythrasma is a 1-year-old infant.

The prognosis for erythrasma is excellent; however, the condition tends to recur if the predisposing factors are not eliminated.

Erythrasma is usually a benign condition. However, it may become widespread and invasive in predisposed and immunocompromised individuals; this is very rare in immunocompetent hosts. In such individuals, this organism has caused infections other than erythrasma. These include abscess formation (3 cases),[10] intravascular catheter–related infections (2 cases),[11] primary bacteremia (3 cases), peritoneal catheter–related infections (2 cases),[11, 12] endocarditis (2 cases),[13, 14] pyelonephritis (2 cases),[15, 16] cellulitis (1 case),[17] endophthalmitis (1 case),[18] arteriovenous fistula infection (1 case), cutaneous granuloma (1 case),[19] and meningitis (1 case).[20]

The first case of postoperative intraabdominal infection caused by Corynebacterium minutissimum in an immunocompetent adult host was reported and has been successfully treated with intravenous amoxicillin/sulbactam.[21]

Any patient with erythrasma should be advised to change his or her life style by engaging in exercise and weight loss because obesity is a major risk factor. In addition, personal hygiene and environment acclimatization should be underscored. Wearing cotton garments rather than synthetic fabrics is yet another consideration to keep the sites of predilection dry. Finally, eating healthy and limiting the intake of sugary foods, especially people with diabetes, is an adjuvant to minimize the risk for this disease.[22]

Dark discoloration associated with erythrasma is usually limited to body folds that are naturally moist and occluded. Infection commonly is asymptomatic, but it can be pruritic. The duration of erythrasma ranges from months to years. Widespread involvement of trunk and limbs is possible.

Immunosuppressed patients with erythrasma and the risk of complications are of special concern. Evaluate and treat possible concomitant infection. Suspect diabetes in recurrent erythrasma. Address and modify risk factors for successful treatment.

The typical appearance of erythrasma is well-demarcated, brown-red macular patches. The skin has a wrinkled appearance with fine scales (see the image below).

Lichenification and hyperpigmentation are common. The skin occasionally has a wrinkled appearance with scales. KOH test results are negative. Courtesy of Michael Bryan, MD.

Infection commonly is located on the inner thighs, crural region, scrotum, and toe webs. The axillae, submammary area, periumbilical region, and intergluteal folds are less commonly involved in erythrasma. Toe web lesions appear as maceration, with the fourth interdigital space most frequently affected.[8]

Owing to the association of erythrasma with other corynebacterial skin infections such as pitted keratolysis and trichomycosis axillaris, all body folds and feet should be screened. This association has been investigated in 53 patients with pitted keratolysis who had skin signs of other corynebacterial infections. Erythrasma was encountered in 2 of 53 of this cohort in male patients, whereas trichobacteriosis was noted in 4 of 53. One patient presented simultaneously with all the three conditions.[23]

Note the following possible complications:

• Fatal septicemia in immunocompromised patients with erythrasma

• Infective endocarditis in valvular heart disease patients with erythrasma

• Postsurgical wound infection in erythrasma patients

Wood light examination of erythrasma lesions reveals coral-red fluorescence of lesions. Results may be negative if the patient bathed prior to presentation.[31] Note the image below. The cause of this color fluorescence has been attributed to excess coproporphyrin III synthesis by these organisms, which accumulates in cutaneous tissue and emits a coral-red fluorescence when exposed to a Wood light.[32]

Under Wood lamp examination, the porphyrins produced by the bacteria fluoresce with a coral pink color. A small focus is visible on this photo. If the patient recently has bathed, the pigment may be washed away. In suspicious cases, a repeat examination the following day may be necessary. Courtesy of Michael Bryan, MD.

In culture media composed of 20% fetal bovine serum, 2% agar, 78% tissue culture medium #199, and 0.05% tris, the organisms grow as nonhemolytic, 1- to 1.5-mm smooth colonies. Methylene blue stain may be used to highlight both the fungal spores of pityriasis versicolor and the curved or club-shaped bacterial rods of C minutissimum, the causative agent of erythrasma, in case both organisms coexist.[25]

Comparing the diagnostic yield between Wood lamp examination and Gram stain, it was found that 9% of patients were positive on the former and 15.6% were positive on the latter. Using both Wood lamp examination and Gram staining concurrently resulted in a higher yield of 22.1% for positive patients.[30]

The diphtheroid bacteria that cause erythrasma are present in the horny layer as rods and filaments.[33]

Infection may be treated with topical and/or oral agents. First-line therapy is topical erythromycin or clindamycin, or fusidic acid cream or miconazole cream. However, fusidic acid is not available in the United States, so topical treatment with the other agents mentioned is the standard of care in the United States. In 2017, mupirocin 2% ointment monotherapy was used on a series of 9 male patients twice daily for 2-4 weeks, with complete resolution of their signs and symptoms.[34] Other topical treatments have been tried more recently and include ozonated olive oil every 12 hours for 10 days, with a cure rate of 100%.[35]

Oral erythromycin is usually effective and is a good second-line therapy, as is single-dose clarithromycin or amoxicillin-clavulanate, for systemic treatment.[36]

C minutissimum is generally susceptible to penicillins, first-generation cephalosporins, erythromycin, clindamycin, ciprofloxacin, tetracycline, and vancomycin. However, multiresistant strains have been isolated.[37, 38, 39, 40] In a susceptibility study of 40 patients, several antibiotics were tested, including penicillin G, ampicillin, cefaclor, amoxicillin-clavulanate, ampicillin-sulbactam, tetracycline, erythromycin, ofloxacin, fusidic acid, levofloxacin, and azithromycin. The study revealed statistically significant resistance to erythromycin, azithromycin, penicillin, and ampicillin. Significant susceptibility was statistically found to amoxicillin-clavulanate, cefaclor, and fusidic acid.[36]

In a large double-blind, placebo-controlled, randomized trial, 151 patients older than 18 years were randomized into five groups and were given either erythromycin, single-dose clarithromycin, topical fusidic acid, placebo cream, or placebo tablets. Fusidic acid cream was significantly more effective than other therapies. Additionally, the group that received clarithromycin did better at 48 hours than did the group that received erythromycin. However, there was no statistical difference on day 7 and day 14.[41]

Photodynamic therapy using red light (broadband, peak at 635 nm) has been reported to clear erythrasma in 23% of 13 patients and to improve erythrasma in the remaining patients; however, it is not the treatment of choice.

The goals of pharmacotherapy for erythrasma are to reduce morbidity, eradicate the infection, and prevent complications.

Class Summary

Antibacterial and/or antifungal agents are used to eradicate C minutissimum and possible concomitant infection.

Erythromycin (E.E.S., E-Mycin, Ery-Tab)

Erythromycin is the drug of choice. It inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest. In children, age, weight, and severity of infection determine the proper dosage. When twice-daily dosing is desired, half the total daily dose may be taken every 12 hours. For more severe infections, double the dose.

Clarithromycin (Biaxin)

Clarithromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Clindamycin (Cleocin)

Clindamycin has a bacteriostatic effect; it interferes with bacterial protein synthesis similarly to erythromycin and chloramphenicol by binding to the 50S subunit of bacterial ribosomes.

Tetracycline (Achromycin)

Tetracycline inhibits cell growth by inhibiting mRNA translation. It binds to the 16S part of 30S ribosomal subunits and prevents amino-acyl tRNA from binding to the A site of ribosomes. Binding is reversible in nature.

Clindamycin topical (Cleocin T, Clindacin P, ClindaDerm)

Clindamycin is an antibacterial agent that binds to the 50S ribosomal subunits of susceptible bacteria and prevents elongation of peptide chains by interfering with peptidyl transfer, thereby suppressing protein synthesis.

Erythromycin topical (AkneMycin, Ery)

Erythromycin inhibits protein synthesis in susceptible organisms by reversibly binding to 50 S ribosomal subunits, thereby inhibiting translocation of aminoacyl transfer-RNA and inhibiting polypeptide synthesis.

Class Summary

Antibacterial and/or antifungal agents are used to eradicate C minutissimum and possible concomitant infection.

Miconazole topical (Femazole, Lotrimin, Monistat)

Miconazole damages the fungal cell wall membrane by inhibiting the biosynthesis of ergosterol. Membrane permeability is increased, causing nutrients to leak out and resulting in fungal cell death. Lotion is preferred in intertriginous areas. If cream is used, apply sparingly to avoid maceration effects. Use 2% cream.