A 54-year-old Caucasian man presents for examination with a 2-year history of multiple, well-defined, erythematous plaques with fine scale on his abdomen and groin. The patient states that these lesions are very itchy and have significantly increased in size during the past several months. He has not tried any topical medications for the lesions. His medications include a daily multivitamin and fish oil, and he has no other significant medical history.
A 28-year-old Hispanic man presents with a 2-week history of multiple erythematous lesions on his right leg. The lesions are pruritic, scaly, and approximately 2 centimeters in diameter. The patient has noticed a slight increase in size of the lesions during the past week. He tried an OTC corticosteroid cream, but the lesions became larger and more inflamed. He spent the past year working in Costa Rica and recently returned. He is otherwise healthy and has no other medical problems.
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Case #1: Mycosis fungoides
Mycosis fungoides (MF), also known as Alibert-Bazin syndrome, was first documented in 1806 by the French dermatologist Jean-Louis Alibert, who described multiple lesions with a mushroom-like appearance.1 The name “mycosis fungoides” is a misnomer, as it implies a fungal etiology; however, MF is the most common form of primary cutaneous T-cell lymphoma.2 There are more than 20 identified variants of MF, each possessing distinct clinical and/or histopathologic features of classic MF.6 However, only 3 variants (folliculotropic, pagetoid reticulosis, and granulomatous slack skin) were included in the 2016 World Health Organization update on the classification of cutaneous lymphomas.6
MF most commonly affects adults, with a median age of diagnosis between 55 and 60 years of age.3 However, MF has also been reported in children and adolescents.3 Incidence rates are significantly more prevalent in men compared with women (1.9:1) and tend to affect African Americans more than Caucasians (1.5:1).9
Despite extensive research on the causative agents of MF, no definitive cause has been found.7 The pathogenesis of MF is thought to be a result of persistent antigen stimulation, which results in atypical clonal T-cell proliferation and excessive helper-memory T-cell accumulation.2,3,7 It is hypothesized that keratinocytes play a role in initiation of the skin lesions seen in mycosis fungoides.7 Injury to keratinocytes results in the release of cytokines and chemokines and downstream T-cell migration to the area of damage.
T-cells then proliferate and accumulate in areas of the epidermis.7 Another theory proposed by Talpur et al (2008) suggests that certain bacteria, such as Staphylococcus aureus, contain enterotoxins that function as superantigens.8 These enterotoxins stimulate T-cell clonal expansion and can drive a cutaneous T-cell lymphoma such as MF.8
MF is an indolent disorder with an unpredictable, slow progression over years to decades.4,5 Classically, MF has 3 stages: patch, plaque, and tumor.5 The clinical presentation of MF is variable; patients may remain in the patch stage without progression, advance linearly through the stages, or present with all 3 stages of the disorder concurrently.6
The patch stage of MF typically presents as well-defined, irregular, erythematous patches commonly localized to the buttocks, breasts, groin, and other sun-protected areas.3 These lesions are often pruritic, with secondary scale and evidence of dyspigmentation.3,7 Poikiloderma, telangiectasia, and atrophy are often defining features of early-stage MF.10 MF advances to the plaque stage when lesions become larger, more discernible, and infiltrated; further progression to nodules and tumors results in a diagnosis of the tumor stage.12 The most common presentation seen concurrently is that of patches and plaques.13 It is rare for MF to immediately present with only tumors, without preceding or concomitant patches or plaques.5
An early diagnosis of MF is often challenging due to its highly variable presentation and nonspecific clinical and histologic aspects.10 Various skin biopsies taken from patients on the same day, from different regions of the body, have shown distinct histologic aspects.11 Therefore, a combination of clinical, histologic, molecular, and immunopathologic criteria should be considered.10
Skin biopsies most often demonstrate with an accumulation of helper T-cells (CD3+, CD4+, and CD45RO+) and a loss of CD7 antigen.14 Under microscopy, early-stage patches show atypical, band-like lymphocytic infiltrates in the basal layer of the epidermis (stratum basale), with markedly indented and sometimes hyperchromatic nuclei.5,6 In the plaque stage, epidermotropism becomes more pronounced and lymphocytes can aggregate to form Pautrier microabscesses; in the tumor stage, epidermotropism is diminished and replaced with larger, more diffuse dermal infiltrates.5
Molecular studies, such as polymerase chain reaction, can confirm the diagnosis of MF if dominant T-cell clones are identified within the skin.10 Dominant T-cell clones can be recognized through the detection of alpha-beta or gamma-delta gene rearrangements of the T-cell receptor.3 Clonality is seen in roughly half of patients in the patch stage and in the majority of patients in each of the plaque and tumor stages.3
The differential diagnosis of MF includes nummular eczema, tinea corporis, small plaque parapsoriasis, plaque psoriasis, lichen simplex chronicus, dimorphous leprosy, vitiligo, pityriasis rosea, and pityriasis lichenoides.3,10,12,15 Due to the variable presentation of MF, a detailed physical examination, skin biopsies, serology, immunohistochemistry, and other analyses should be used to rule out or confirm these well-defined skin disorders.7,12
The treatment of MF is based on the tumor-node-metastasis-blood (TNMB) clinical staging system.4 MF is generally considered to be an incurable disease, but treatment regimens can afford patients with early-stage MF more than 12 years of survival.4 Depending on the stage of MF, first-line therapy can include: topical corticosteroids (class III-IV), UV phototherapy (systemic or topical psoralen and ultraviolet A [PUVA]), and local radiotherapy (>30 Gy).16 In more advanced clinical stages, MF can spread to the lymph nodes, visceral organs, or blood, often resulting in a poor prognosis with less than 5 years of survival.4 Treatment options for advanced clinical stages include a combination of PUVA with interferon-alpha, topical retinoids (bexarotene), chlorambucil, corticosteroids, or local radiotherapy (>30 Gy).16 However, even aggressive chemotherapy treatment has not been shown to improve the prognosis of patients with advanced-stage MF.17
The patient in this vignette was biopsied and diagnosed with plaque-stage MF. The patient was started on phototherapy to which he responded. The patient is currently doing well and is being maintained on phototherapy treatments.
Case #2: Tinea corporis
Fungal (tinea) infections are estimated to affect more than 20% to 25% of the world’s population and are classically named according to their clinical localization.18 Tinea corporis, also referred to as ringworm, includes all dermatophyte infections of the glabrous skin, excluding the scalp, beard, groin, hands, and feet.19 The term “tinea” refers to any type of fungal infection, while the term “corporis” comes from the Latin word meaning “body.”19 The dominant species of dermatophytes that cause tinea corporis include: Trichophyton rubrum, Microsporum canis, and Trichophyton tonsurans.18 There are 3 sources of infection by dermatophytes: humans (anthropophilic), animals (zoophilic), and soil (geophilic); all 3 types can infect humans via direct or indirect contact.21
Dermatophytes particularly thrive in warm and humid conditions; therefore, fungal infections are commonly seen in tropical climates.18 Individuals who sweat excessively, wear tight-fitting clothing, are exposed to infected animals, or participate in contact sports have an increased risk of contracting tinea corporis.18,20 Tinea corporis more commonly affects children than adults, and is more frequently found in communities of lower social, economic, or educational status.18
Dermatophytes, such as those causing tinea corporis, are able to adhere to the epithelial tissue of the host using mannan glycoproteins.22 Dermatophytes are able to further infect the host by invading the stratum corneum (further proliferating within the epidermis) and degrading the cytokeratin using keratinase, cysteine dioxygenase, and a sulfite efflux pump.22 Dermatophytes are typically unable to colonize tissue layers below the stratum corneum or organs of an immunocompetent host and therefore generally will not advance past a cutaneous infection.23
Tinea corporis typically presents as an erythematous, ring-shaped, scaly, pruritic patch with a raised leading edge and a clear center.19 Tinea corporis may present as single lesions or multiple lesions ranging from 1 to 5 centimeters in size.19 Lesions progress outward from the borders, and multiple lesions may join together to form larger lesions.24 Tinea corporis typically presents in exposed areas of the skin, such as the arms, legs, and abdomen.18 In addition to observing a patient’s physical presentation and obtaining a thorough history, a microscopic observation and fungal culture should be performed to establish a diagnosis.25
The primary methods of diagnosis of tinea corporis include: clinical inspection, microscopic examination of skin scrapings (with a 5% to 20% potassium hydroxide solution [KOH]), and fungal culture on a suitable medium.24
A light scraping of the lesion should be placed on a microscope slide, after which a potassium hydroxide solution should be added.19 The potassium hydroxide solution dissolves squamous cells, leaving behind any fungi.19 A positive skin biopsy should reveal fungal elements such as hyphae and mycelia (septate, tube-like structures).24 For atypical or incessant lesions, microscopic examination with periodic acid-Schiff stain may be indicated.19
Fungal cultures are more sensitive than the potassium hydroxide preparation.19 A culture can be prepared by sampling the affected area using a moist cotton applicator, which is then applied to a suitable medium such as Sabouraud’s dextrose agar.19 Positive fungal cultures incubated at room temperature should grow evidence of fungal elements within 2 weeks.20
Clinical examination of tinea corporis can often be misdiagnosed due to its similar appearance to other skin disorders.19 The persistence or worsening of a dermal infection despite the use of a topical steroid cream should raise suspicion of a dermatophyte infection.19 The differential diagnosis of tinea corporis includes annular psoriasis, atopic dermatitis, mycosis fungoides, erythema multiforme, granuloma annulare, lupus erythematosus, nummular eczema, pityriasis rosea herald patch, and seborrheic dermatitis.19 Due to the number of disorders that can mimic tinea corporis, microscopy with potassium hydroxide preparation, along with a fungal culture, can be used to confirm a diagnosis of tinea corporis.19,20
Tinea corporis is typically treated with topical anti-fungal creams, including the azoles (itraconazole, ketoconazole, sulconazole, oxiconazole, miconazole, clotrimazole, econazole), allylamines (naftifine, terbinafine), benzylamines (butenafine), and hydroxypyridones (ciclopirox olamine).20 Due to shorter treatment times, fungicidal drugs such as allylamines and benzylamines may be favored against fungistatic drugs such as azoles.26 Additionally, since patients often discontinue treatment early, when the disorder appears to be healed, tinea corporis is less likely to recur when a fungicidal drug is used.26 A response to topical creams can typically be seen following 2 weeks of treatment, and continuation of treatment for 1 week following infection clearance is recommended.24 Additionally, systemic treatment may be indicated for patients who are immunocompromised, have extensive disease, or did not respond to topical creams.19
A KOH prep was performed on the patient in the previous vignette. Fungal elements were visualized and the patient was prescribed topical terbinafine 1% cream. The patient’s rash resolved within 3 weeks.
Jessica Tran is a medical student, Emma Weiss is a medical student, and Christopher Rizk, MD, is a dermatology resident at the Baylor College of Medicine in Houston.
- Karamanou M, Psaltopoulou T, Tsoucalas G, Androutsos G. Baron Jean-Louis Alibert (1768-1837) and the first description of mycosis fungoides. J BUON. 2014;19:585-588.
- Yawalkar N, Ferenczi K, Jones DA, et al. Profound loss of T-cell receptor repertoire complexity in cutaneous T-cell lymphoma. Blood. 2003;102:4059-4066.
- Jawed SI, Myskowski PL, Horwitz S, Moskowitz A, Querfeld C. Primary cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome): part I. Diagnosis: clinical and histopathologic features and new molecular and biologic markers. J Am Acad Dermatol. 2014;70:205e1-16.
- Mazzeo E, Rubino L, Buglione M, et al. The current management of mycosis fungoides and Sézary syndrome and the role of radiotherapy: Principles and indications. Rep Pract Oncol Radiother. 2014;19:77-91.
- Willemze R, Jaffe ES, Burg G, et al. WHO-EORTC classification for cutaneous lymphomas. Blood. 2005;105:3768-3785.
- Muñoz-González H, Molina-Ruiz AM, Requena L. Clinicopathologic variants of micosis fungoides. Actas Dermosifiliogr. 2017;108:192-208.
- Girardi M, Heald PW, Wilson LD. The pathogenesis of mycosis fungoides. N Engl J Med. 2004;350:1978-1988.
- Talpur R, Bassett R, Duvic M. Prevalence and treatment of Staphylococcus aureus colonization in patients with mycosis fungoides and Sézary syndrome. Br J Dermatol. 2008;159:105-112.
- Criscione VD, Weinstock MA. Incidence of cutaneous T-cell lymphoma in the United States, 1973-2002. Arch Dermatol. 2007;143:854-859.
- Pimpinelli N, Olsen EA, Santucci M, et al. Defining early mycosis fungoides. J Am Acad Dermatol. 2005;53:1053-1063.
- Massone C, Kodama K, Kerl H, Cerroni L. Histopathologic features of early (patch) lesions of mycosis fungoides: a morphologic study on 745 biopsy specimens from 427 patients. Am J Surg Pathol. 2005;29:550-560.
- Wollenberg A, Eames T. Skin diseases following a Christmas tree pattern. Clin Dermatol. 2011;29:189-194.
- Cho-Vega, JH, Tschen JA, Duvic M, Vega F. Early-stage mycosis fungoides variants: case-based review. Ann Diagn Pathol. 2010;14:369-385.
- Nikolaou VA, Papadavid E, Katsambas A, et al. Clinical characteristics and course of CD8+ cytotoxic variant of mycosis fungoides: a case series of seven patients. Br J Dermatology. 2009;161:826-830.
- Yamashita T, Abbade LP, Marques MEA, Marques SA. Mycosis fungoides and Sézary syndrome: clinical, histopathological and immunohistochemical review and update. An Bras Dermatol. 2012;87:817-830.
- Dugas-Breit S, Schulze HJ, and Hallermann C. New and established treatment options for mycosis fungoides and Sézary syndrome—an update. J Dtsch Dermatol Ges. 2014;12:561-569.
- Kaye FJ, Bunn PA Jr, Steinberg SM et al. A randomized trial comparing combination electron-beam radiation and chemotherapy with topical therapy in the initial treatment of mycosis fungoides. N Engl J Med. 1989;321:1784-1790.
- Havlickova B, Czaika VA, Friedrich M. Mycoses: Epidemiological trends in skin mycoses worldwide. Mycoses. 2008;51(suppl 4):2-15.
- Ely JW, Rosenfeld S, Seabury Stone M. Diagnosis and management of tinea infections. Am Fam Physician. 2014;90:702-710.
- Gupta AK, Chaudhry M, Elewski B. Tinea corporis, tinea cruris, tinea nigra, and piedra. Dermatol Clin. 2003;21:395-400.
- Segal E, Frenkel M. Dermatophyte infections in environmental contexts. Res Microbiol, 2015;166:564-569.
- Nenoff P, Krüger C, Ginter-Hanselmayer G, Tietz HJ. Mycology—an update. Part 1: Dermatomycoses: causative agents, epidemiology and pathogenesis. J Dtsch Dermatol Ges. 2014;12:188-210.
- Surendran K, Bhat RM, Boloor R, Nandakishore B, Sukumar D. A clinical and mycological study of dermatophytic infections. Indian J Dermatol. 2014;59:262-267.
- Kaushik N, Pujalte GG, Reese ST. Superficial fungal infections. Prim Care. 2015;42: 501-516.
- Van Zuuren EJ, Fedorowicz Z, El-Gohary M. Evidence-based topical treatments for tinea cruris and tinea corporis: a summary of a Cochrane systematic review. Br J Dermatol, 2015;172:616-641.
- Kyle AA, Dahl MV. Topical therapy for fungal infections. Am J Clin Dermatol. 2004;5:443-451.