Treating Rare Fungal Infections: Majocchi’s Granuloma
Taken from the 4th annual postgraduate course and workshop in medical mycology-dermatomycology, July 27-30, 1979, Newport Beach, CA. Dr. James H. Graham was the former head of dermatopathology at the Armed Forces Institute of Pathology and the former chair of dermatology at UC-Irvine.
He has made available his personal library of kodachromes, slides and lectures collected throughout his career by means of a generous donation to the Wake Forest University Baptist Medical Center library. Dr. Graham’s lectures and personal images in dermatomycology will be highlighted in this series to refresh the practicing clinician on deep cutaneous mycotic disease.
Majocchi’s granuloma (MG), also known as nodular granulomatous perifolliculitis, is an uncommon fungal folliculitis that was first reported by Professor Domenico Majocchi in 1883. 1 It has been described as, “certain superficial fungus diseases which sometimes exhibit fungal elements invading the epidermis, pilosebaceous follicles and dermis to mimic deep cutaneous mycotic disorders.” 2 The most common dermatophyte implicated in MG is Trichophyton rubrum; however, several organisms have been reported predominantly in the Trichophyton and Microsporum genera (Table 1). Risk factors for MG appear to highlight a host’s immune susceptibility, either local or generalized.
Affected areas tend to include the scalp, beard area of the face and hair-bearing skin of the extremities, but MG can affect any area of the body. A classical presentation is a woman who shaved her legs and later developed follicular papules, pustules or nodules in the area (Figure 1).3,4 The lesions can be single or multiple, follow a folliculocentric pattern, and some may be tender. Two clinical variants have been described. The first is a follicular type secondary to local immunosuppression from topical steroid use. 5 Clinical presentation in immunocompetent patients usually reveals a flesh-colored or erythematous, granulomatous lesion. 6 There have been interesting reports of MG in otherwise immunocompetent individuals. One patient developed MG of the scrotum after using corticosteroids to self-treat tinea cruris. 3 MG became secondarily infected on the abdomen of a courier after consistently handling animal waste and also in someone who regularly handled infected rabbits (Figure 2).2,7 The second type is a subcutaneous nodular variant due to systemic immunocompromise from atopic dermatitis, chemotherapy for hematologic malignancy, autoimmune disease or patients with solid-organ transplants. 5,8,9 Those who are immunocompromised tend to have more variable lesions including plaques, subcutaneous nodules and abscesses. 6,10 There are multiple presentations of Majocchi’s granuloma (Table 2). Typical presentations include two clinical variants, papules and subcutaneous nodules. However, MG can range clinically from only erythema to timorous granulomas and plaques. It is especially important to keep in mind the variation of lesions when dealing with immunocompromised patients.
Histologically, MG appears as foci of granulomatous inflammation that exhibit epidermal and dermal features similar to those seen in deep cutaneous mycotic diseases (Figures 3 and 4).2 Fungal elements will be present in the dermis, and arthrospores and segmented hyphae can be visualized. The arthrospores may appear bizarre with odd branching hyphae and some may be clumped together as mycotic granules (Figures 5 and 6). Occasionally, arthrospores show radiate formation of fungal elements in deep dermal abscesses. The fungal elements have histochemical characteristics due to the presence of neutral polysaccharides and nonsulfated acid mucosaccharides, which has been attributed to sialomucin produced by the arthrospore. 2,6,11 The histopathology of Majocchi’s granuloma depends on the duration of disease and can have several histological presentations that vary from the above- mentioned general granulomatous pattern (Table 3). No correlation has been found between a certain histological presentation and the specific organism involved. 6 Also, there are no specific histological changes found in more immunocompromised patients, but more organisms are usually present and there is typically less of a granulomatous reaction. 6
Based on the clinical morphology, the differential diagnosis largely includes other conditions that follow a follicular pattern, such as variations of folliculitis, acne, pseudofolliculitis barbae, eosinophilic pustular folliculitis and acne keloidalis (Table 4). Lesions that are more granulomatous may be mistaken as lymphadenopathy and as part of a lymphoproliferative disorder. 8 The differential diagnosis for the causative agent includes dermatophytes, which produce endo-ectothrix and endothrix infections (Table 1). Trichophyton rubrum is the most common pathogen in both variants and is isolated in roughly 80% of MG cases in immunosuppressed individuals. 2,8 Species of Trichophyton and Microsporum are commonly implicated etiologic agents; however, Aspergillus has also been reported. 10 There is no way to determine the specific fungal organism involved by clinical inspection alone. Biopsy is often indicated to make the final diagnosis, and fungal culture can help identify the responsible organism. Periodic acid-Schiff and Gomori methenamine silver stains can identify fungal elements in the epidermis and dermis as well as help define the fungal organisms. The histopathological differential diagnosis includes tissue reaction patterns similar to most of the deep cutaneous mycoses. 2 The clinical differential diagnosis may have overlapping diseases with the histopathological differential, and include those entities that resemble a form of follicular pathology, such as cystic acne, perifolliculitis capitis abscendens et suffodiens, hidradenitis suppurativa and folliculitis keloidalis (Table 5). Atypical Mycobacterium infection, staphylococcic actinophytosis (botyromycosis), and candida granuloma can also have similar pathology.
Treatment of Majocchi’s granuloma generally involves oral antifungals, since the process involves deeper portions of the dermis and subcutaneous tissue that topical treatment alone may not be able to penetrate. 3,12 However, there are reports of successful topical antifungal treatment of a superficial type MG of the scrotum, and thus this may be an option for monotherapy, or used in conjunction with oral antifungals. 3,4,13 Oral antifungals used in treatment include terbinafine, griseofulvin and pulsed itraconazole, and typically responds well to any of these regimens (Table 6).3,14 High levels of terbinafine have been detected in the stratum corneum and hair follicles within 24 hours of initiating therapy. 14 Terbinafine’s selectivity for skin structures involved in MG makes it the preferred oral therapy, additionally because it has less drug interactions that azole antifungals like itraconazole. 13,14 With any chosen therapeutic modality, successful treatment of Majocchi’s granuloma also involves feasible avoidance of any causative immunosuppressant agent such as erroneous local application of topical steroids. 1
• Majocchi’s granuloma is an uncommon deep cutaneous mycotic infection most commonly caused by Trichophyton rubrum. • There are two clinical variants of Majocchi’s granuloma, an erythematous, granulomatous lesion found in immunocompetent hosts and a subcutaneous nodular variant found in the immunocompromised. • Diagnosis relies on biopsy, which demonstrates fungal elements in the stratum corneum and dermis within a granulomatous histology pattern. • Fungal elements can be viewed on H&E, but PAS and GMS stains can also be used. • Histology alone cannot identify the causative organism, but fungal culture can confirm the suspected fungus. • Treatment includes oral antifungal therapy with terbinafine, griseofulvin or pulsed itraconazole. Ms. Feneran is a medical student at Wake Forest University School of Medicine in Winston-Salem, NC, and is associated with the Center for Dermatology Research there. Dr. Dabade is with the Center for Dermatology Research, Department of Dermatology, Wake Forest University School of Medicine; Winston-Salem, NC. Dr. Feldman is with the Center for Dermatology Research, and the Departments of Dermatology, Pathology and Public Health Sciences at Wake Forest University School of Medicine, Winston-Salem, NC. The Center for Dermatology Research is supported by an unrestricted educational grant from Galderma Laboratories, L.P. Disclosures: Drs. Feneran, Dabade, and Feldman disclose that they have no real or apparent conflicts of interest or financial interests or arrangements with any companies or products mentioned in this article.