A common chronic, noninflammatory and usually symptomless disorder, characterized by the occurrence of multiple macular patches of all sizes and shapes, and varying in pigmentation from fawn-colored to brown. It is seen most frequently in hot, humid, tropical regions and is mostly caused by Malassezia Furfur (formerly Pityrosporum orbiculare).

Introduction

Pityriasis versicolor, also known as tinea versicolor, is a frequent, benign, superficial fungal infection of the skin. It belongs to Malassezia-related diseases. Clinical features of pityriasis versicolor include either hyperpigmented or hypopigmented finely scaly macules. The most frequently affected sites are the trunk, neck, and proximal extremities. The diagnosis of pityriasis versicolor is often made on clinical grounds alone. The ultraviolet black light and the microscopic examination of scales soaked in potassium hydroxide may be helpful in doubtful cases. Pityriasis versicolor responds well to induction therapy. However, long-term maintenance treatment often is required because of high recurrence rate.

Etiology

Pityriasis versicolor is caused by Malassezia, a dimorphic lipophilic fungus, also known as Pityrosporum. It is a component of normal skin flora. To date, 14 species of Malassezia have been identified.The main species isolated in pityriasis versicolor are Malassezia furfur, Malassezia globosa, Malassezia sympodialis.

Epidemiology

Pityriasis versicolor has been reported worldwide, but it is more common in warm and humid conditions. The prevalence is as high as 50% in tropical countries and as low as 1.1% in cold climates such as Sweden. Pityriasis versicolor occurs more frequently in adolescents and young adults probably due to the increase of sebum production by the sebaceous glands which allow for a more lipid-rich environment in which Malassezia can grow. Pityriasis versicolor affects men and women equally and no specific ethnic predominance has been noted.

Pathophysiology

Malassezia is commensal of healthy skin, and it is most common in oily areas such as the face, scalp, and back. However, Malassezia can cause pityriasis versicolor when it converts to its pathogenic filamentous form. Factors that lead to this pathogenic conversion include a genetic predisposition, environmental conditions such as heat and humidity, immunodeficiency, pregnancy, oily skin, and application of oily lotions and creams.

Histopathology

A skin biopsy is not required to confirm a diagnosis, but if it is performed, histological findings include hyperkeratosis, acanthosis, and a mild superficial, perivascular infiltrate in the dermis. Fungal elements are localized almost exclusively within the stratum corneum and can often be visualized even in sections stained with hematoxylin-eosin. Both spores and hyphae of Malassezia are present and are often likened to spaghetti and meatballs. Periodic acid-Schiff stain may improve recognition of the fungus.

History and Physical

Patients with pityriasis versicolor present with multiple, well-demarcated, oval, finely scaling patches or plaques. Skin lesions may be hypopigmented, hyperpigmented, or erythematous and occasionally become confluent and widespread. The fine scale may not be readily apparent on the lesions, but it is easily provoked when the affected skin is stretched or scraped. The distribution of affected skin reflects the lipophilic nature of the fungus since the seborrheic areas (trunk, neck, and/or arms) are predominantly involved. The face also may be affected, particularly in children. Pityriasis versicolor skin lesions are usually asymptomatic or slightly pruritic. However, severe pruritus can be present in very warm and humid conditions.

Evaluation

Diagnosis of pityriasis versicolor is usually easily made on the basis of its characteristic clinical presentation (hyperpigmented or hypopigmented, finely scaling patches or plaques).

The ultraviolet black light (Wood lamp) may help to demonstrate the coppery-orange fluorescence of pityriasis versicolor.

The diagnosis is confirmed by microscopic examination of scales soaked in potassium hydroxide examination, which demonstrates the typical grape-like clusters of yeast cells and long hyphae. Since the standard potassium-hydroxide mount lacks a color contrast, methylene blue stain, ink blue stain, or Swartz-Medrik stain may be added to visualize better.

Malassezia species are known to be difficult to grow in the laboratory as they require fastidious culture conditions.

Treatment / Management

Patients should be informed that the causative agent of pityriasis versicolor is a commensal fungal inhabitant of the normal skin flora, and therefore the disease is not considered to be contagious. In addition, pityriasis versicolor does not lead to either permanent scarring or pigmentary disorders. However, in many cases, disease recurrence may occur despite effective treatment.

Pityriasis versicolor may be treated effectively with topical and/or systemic agents.

Topical medications are considered the first-line therapy for pityriasis versicolor. Topical treatments are divided into nonspecific antifungal agents (sulfur plus salicylic acid, selenium sulfide 2.5%, and zinc-pyrithione) that primarily remove dead tissue and prevent further invasion, and specific antifungal drugs, that have fungicidal or fungistatic effects. Antifungal agents include imidazole (clotrimazole 1%, ketoconazole 2%, econazole, isoconazole, miconazole), ciclopirox olamine 1% , and allylamine (terbinafine 1%). Galenic forms such as sprays or foaming solutions in shampoo are preferable to creams because creams are oilier and more difficult to apply, especially in widespread areas. Ketoconazole is the most common topical treatment used to treat pityriasis versicolor. It can be applied as a cream (twice daily for 15 days) or in a foaming solution (single dose).

Oral medications are viewed as a second-line of treatment for pityriasis versicolor in the event of widespread, severe, recalcitrant or recurrent cases. Systemic therapies include itraconazole (200 mg daily for seven days) and fluconazole (150 to 300 mg weekly dose for 2 to 4 weeks) that are preferred to oral ketoconazole which is no longer approved due to its potential hepatotoxic sides effects. Oral terbinafine is not effective in the treatment of pityriasis versicolor.

In cases of recurrent pityriasis versicolor, maintenance therapy may be necessary. Topical prophylactic treatment can be used. However, systemic antifungal agents are preferred since they are less time-consuming and ensure better compliance. Many studies have been conducted to identify the best prophylactic regimen.

Differential Diagnosis

Pityriasis versicolor may be confused with various conditions:

• Pityriasis rosea

• Tinea corporis

• Vitiligo

• Pityriasis alba

• Confluent reticulated papillomatosis of Gougerot and Carteaud

• Postinflammatory hypo- and hyperpigmentation

• Seborrheic dermatitis

• Guttate psoriasis

• Tinea corporis

• Nummular eczema

• Secondary syphilis

• Mycosis fungoides

Prognosis

Pityriasis versicolor is benign and noncontagious since the causative fungal pathogen is commensal of normal skin. Oral and topical antifungal agents are effective; however, disease recurrence is common and may have an impact on a patient's quality of life. Therefore, preventive measures should be taken. Also, patients must be reminded that pigmentary changes may take weeks to months to clear, even if the fungus is eradicated.

Pearls and Other Issues

Pityriasis versicolor is a benign but commonly recurrent superficial fungal infection of the skin. Therefore, patients need effective follow-up care to implement a relapse prevention strategy.

Enhancing Healthcare Team Outcomes

Tinea versicolor is a relatively common skin disorder that may be encountered by the nurse practitioner, internist, dermtologist and primary care physician. The diagnosis is usually made on clinical features but does require clinical acumen. The rash is benign and may spontaneously disappear.

Patients should be informed that the causative agent of pityriasis versicolor is a commensal fungal inhabitant of the normal skin flora, and therefore the disease is not considered to be contagious. In addition, pityriasis versicolor does not lead to either permanent scarring or pigmentary disorders. However, in many cases, disease recurrence may occur despite effective treatment. An interprofessional team of a nurse and clinician should provide patient education which will decrease their anxiety and provide the best patient outcome.

The outcomes in most patients are excellent.

The most common mode of action for antifungal drugs is the disruption of the cell membrane. Antifungals take advantage of small differences between fungi and humans in the biochemical pathways that synthesize sterols. The sterols are important in maintaining proper membrane fluidity and, hence, proper function of the cell membrane. For most fungi, the predominant membrane sterol is ergosterol. Because human cell membranes use cholesterol, instead of ergosterol, antifungal drugs that target ergosterol synthesis are selectively toxic (Figure 14.13).

Figure 14.13 The predominant sterol found in human cells is cholesterol, whereas the predominant sterol found in fungi is ergosterol, making ergosterol a good target for antifungal drug development.

The imidazoles are synthetic fungicides that disrupt ergosterol biosynthesis; they are commonly used in medical applications and also in agriculture to keep seeds and harvested crops from molding. Examples include miconazole, ketoconazole, and clotrimazole, which are used to treat fungal skin infections such as ringworm, specifically tinea pedis (athlete’s foot), tinea cruris (jock itch), and tinea corporis. These infections are commonly caused by dermatophytes of the genera Trichophyton, Epidermophyton, and Microsporum. Miconazole is also used predominantly for the treatment of vaginal yeast infections caused by the fungus Candida, and ketoconazole is used for the treatment of tinea versicolor and dandruff, which both can be caused by the fungus Malassezia.

The triazole drugs, including fluconazole, also inhibit ergosterol biosynthesis. However, they can be administered orally or intravenously for the treatment of several types of systemic yeast infections, including oral thrush and cryptococcal meningitis, both of which are prevalent in patients with AIDS. The triazoles also exhibit more selective toxicity, compared with the imidazoles, and are associated with fewer side effects.

The allylamines, a structurally different class of synthetic antifungal drugs, inhibit an earlier step in ergosterol biosynthesis. The most commonly used allylamine is terbinafine (marketed under the brand name Lamisil), which is used topically for the treatment of dermatophytic skin infections like athlete’s foot, ringworm, and jock itch. Oral treatment with terbinafine is also used for the treatment of fingernail and toenail fungus, but it can be associated with the rare side effect of hepatotoxicity.

The polyenes are a class of antifungal agents naturally produced by certain actinomycete soil bacteria and are structurally related to macrolides. These large, lipophilic molecules bind to ergosterol in fungal cytoplasmic membranes, thus creating pores. Common examples include nystatin and amphotericin B. Nystatin is typically used as a topical treatment for yeast infections of the skin, mouth, and vagina, but may also be used for intestinal fungal infections. The drug amphotericin B is used for systemic fungal infections like aspergillosis, cryptococcal meningitis, histoplasmosis, blastomycosis, and candidiasis. Amphotericin B was the only antifungal drug available for several decades, but its use is associated with some serious side effects, including nephrotoxicity (kidney toxicity).

Amphotericin B is often used in combination with flucytosine, a fluorinated pyrimidine analog that is converted by a fungal-specific enzyme into a toxic product that interferes with both DNA replication and protein synthesis in fungi. Flucytosine is also associated with hepatotoxicity (liver toxicity) and bone marrow depression.

Beyond targeting ergosterol in fungal cell membranes, there are a few antifungal drugs that target other fungal structures (Figure 14.14). The echinocandins, including caspofungin, are a group of naturally produced antifungal compounds that block the synthesis of β(1→3) glucan found in fungal cell walls but not found in human cells. This drug class has the nickname “penicillin for fungi.” Caspofungin is used for the treatment of aspergillosis as well as systemic yeast infections.

Although chitin is only a minor constituent of fungal cell walls, it is also absent in human cells, making it a selective target. The polyoxins and nikkomycins are naturally produced antifungals that target chitin synthesis. Polyoxins are used to control fungi for agricultural purposes, and nikkomycin Z is currently under development for use in humans to treat yeast infections and Valley fever (coccidioidomycosis), a fungal disease prevalent in the southwestern US.

The naturally produced antifungal griseofulvin is thought to specifically disrupt fungal cell division by interfering with microtubules involved in spindle formation during mitosis. It was one of the first antifungals, but its use is associated with hepatotoxicity. It is typically administered orally to treat various types of dermatophytic skin infections when other topical antifungal treatments are ineffective.

There are a few drugs that act as antimetabolites against fungal processes. For example, atovaquone, a representative of the naphthoquinone drug class, is a semisynthetic antimetabolite for fungal and protozoal versions of a mitochondrial cytochrome important in electron transport. Structurally, it is an analog of coenzyme Q, with which it competes for electron binding. It is particularly useful for the treatment of Pneumocystis pneumonia caused by Pneumocystis jirovecii. The antibacterial sulfamethoxazole-trimethoprim combination also acts as an antimetabolite against P. jirovecii.

Table 14.7 shows the various therapeutic classes of antifungal drugs, categorized by mode of action, with examples of each.

Figure 14.14 Antifungal drugs target several different cell structures. (credit right: modification of work by “Maya and Rike”/Wikimedia Commons)

Table14.7

Vitiligo is not the only disease that causes skin to change color.

Here are a few conditions and what they look like, including vitiligo.

Talk to your health care provider if you think you might have vitiligo or another skin condition.