Primary Cutaneous Infection by avium: A Case Report and Literature Review

Amir Aboutalebi, MD; Angela Shen, MD; Rajani Katta, MD; Sarah E. Allen, MD

Nontuberculous mycobacteria (NTM) are becom- virus (HIV)–negative patients, MAC is primarily ing increasingly important cutaneous pathogens a pulmonary pathogen. In patients with HIV, it as the number of susceptible patients increases. is more commonly disseminated or can present as Nevertheless, primary cutaneous infection by one gastrointestinal tract disease. Mycobacterium avium particular species, Mycobacterium avium com- complex rarely produces cutaneous manifestations in plex (MAC), remains relatively unusual, particu- any patient population. In those exceptional instances larly in immunocompetent patients. We review the of cutaneous expression, skin findings usually are sec- English-language literature on primary cutaneous ondary to disseminated disease2 and are seen almost MAC in patients who were neither immunocompro- exclusively in immunocompromised hosts.2,3 We pre- mised nor pharmacologically immunosuppressed.CUTIS sent a case of a primary cutaneous infection with We offer an additional report of a healthy patient MAC following presumed traumatic inoculation in a who presented to our clinic with primary cutane- healthy patient. ous MAC following seemingly innocuous trauma to the leg. Case Report DoCutis. 2012;89:175-179. NotA 57-year-oldCopy woman presented with an erythema- tous scaly plaque on her right shin. The lesion ini- tially was diagnosed as allergic contact dermatitis and he term nontuberculous mycobacteria (NTM) treated with desoximetasone ointment 0.25%. When defines a heterogeneous group of nonmotile, it failed to improve in 2 months, a biopsy was per- T acid-fast bacilli that are ubiquitous in the formed, which showed stasis dermatitis with superfi- environment. The ever-rising importance of these cial and deep eosinophils and pseudoepitheliomatous organisms mirrors their increased prevalence, which hyperplasia. Accordingly, the patient was treated with comes from mounting numbers of immunosuppressed halobetasol ointment and advised to utilize compres- patients and a rise in surgical procedures. Affected sion stockings. When the lesion persisted, she was individuals may present with pulmonary infection, treated with econazole cream and referred to our lymphadenitis, disseminated disease, skin infection, clinic for patch testing. or hard and soft tissue disease.1 On physical examination, she had an erythema- Regarding cutaneous disease, nearly all species of tous plaque with hyperkeratotic scale on the right NTM have been implicated, including Mycobacterium shin (Figure) and xerotic erythematous patches avium complex (MAC). In human immunodeficiency affecting the right lower leg, left shin, and left foot. Examination was unremarkable for any lymphade- nopathy. The patient denied explicit knowledge of trauma but reported exposure to an organic fertil- From Baylor College of Medicine, Houston, Texas. Drs. Aboutalebi, izer on her legs while gardening prior to the onset Shen, and Katta are from the Department of Dermatology, and of the lesion. Patch testing showed an allergy to a Dr. Allen is from the Department of Medicine, Section of fragrance ingredient, and a repeat open application Infectious Diseases. The authors report no conflict of interest. test by the patient confirmed allergy to econazole Correspondence: Rajani Katta, MD, Baylor Clinic, 6620 Main St, cream. However, these allergic reactions were felt to Ste 1425, Houston, TX 77030. be secondary, and the differential diagnosis included

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Additionally, MAC may gain entry through trau- matic inoculation or result in gastrointestinal tract disease. As with other NTM, immunocompromised patients are particularly susceptible to infection and may exhibit subsequent hematogenous dissemination to the skin, central nervous system, and the reticulo- endothelial system.3 Dissemination typically follows gut infection. Skin infection may be a product of direct inoculation, cervical lymphadenitis with over- lying formation, or disseminated disease.1,4 Mycobacterium avium complex may be isolated from any number of environmental sources including soil, Erythematous scaling plaque on the right shin. freshwater, seawater, dairy products, animal tissues, and house dust.5 Despite its omnipresence and its ability to infect nearly any organ system, MAC tends to be underdiagnosed due to a low index of suspi- Majocchi granuloma, deep fungal infection, myco- cion. Its nonspecific and polymorphous presentation bacterial infection, and , lends itself to misdiagnosis. The differential diagnosis along with superimposed irritant and allergic contact of cutaneous MAC may include other infectious dermatitis. The patient was started on doxycycline and granulomatous diseases such as Mycobacterium hyclate 100 mg orally twice daily, along with des- marinum infection (fish tank granuloma)3; leproma- oximetasone ointment applied to the left shin and tous leprosy6; lupus vulgaris7; sarcoidosis8-10; prurigo petroleum jelly to the right shin. Although the lesions nodularis11; and, as in the present report, dermatitis. resolved elsewhere, the plaque on the right shin pro- There has even been a case report of a particularly gressed to a red plaque with several deep pustules. A uncommon presentation appearing as rosacea.12 second biopsy of the right shin showed pseudoepithe- Clinically, cutaneous disease may present as CUTIS 6 liomatous hyperplasia with intraepidermal and dermal diversely as scaling papules, ulcerated or subcuta- neutrophils as well as increased vasculature. Periodic neous nodules,4,13 ,14 painless ulcers,9 pan- acid–Schiff and Fite stains were negative for fungi and niculitis, ecthymalike lesions, draining sinuses,13 or mycobacteria, respectively. Treatment was initiated granulomatous plaques.7 Distribution also may vary, for suspected mycobacterialDo infection Not with minocy- with Copy most cases of primary cutaneous disease present- cline hydrochloride 100 mg twice daily and hyper- ing with localized skin involvement affecting the thermia therapy in the form of warm compresses. extremities, face, neck, back, and groin, usually spar- Chest radiograph did not reveal any abnormalities. ing the palms and soles.15 Disseminated skin involve- Laboratory investigations (ie, complete blood cell ment has been reported less frequently. Cox and count, thyroid function tests, urinalysis, electrolytes) Strausbaugh16 reported a case of long-term untreated were all within reference range, with the exception of M intracellulare in an immunosuppressed patient that the hematocrit, which was slightly low at 34.3% (ref- progressed to involve large portions of the head and erence range, 35%–45%). Cultures returned positive trunk. Similarly, Epps et al8 reported 2 patients mis- for MAC after 1 month’s duration. diagnosed with sarcoidosis who progressed to develop The infectious disease service was consulted and widespread cutaneous infection. Lugo-Janer et al13 treatment with clarithromycin, ethambutol, and reported a case of disseminated cutaneous MAC rifampin was initiated. After 3 weeks of therapy, the associated with osteomyelitis in a healthy 11-year-old patient’s lesions mildly improved. patient following trauma to the foot. Regarding the clinical pattern, lesions may be solitary or multiple Comment localized cutaneous lesions (nonlymphocutaneous Mycobacterium avium complex collectively refers to lesions at the site of trauma or lesions having a sporo- M avium, Mycobacterium intracellulare, and other trichoid distribution3,15,17) or disseminated cutaneous unnamed species. Although it is the most common lesions. Bartralot et al3 reported that 7 of 29 patients atypical Mycobacterium causing disseminated dis- (24%) without immunologic deficiencies had more ease, MAC rarely is implicated in primary cutaneous than 1 type of presenting lesion; overall, healthy lesions. Because its preferred means of contagion is patients had fewer lesions and more localized disease the respiratory tract, MAC is commonly associated in comparison to immunosuppressed patients. with pulmonary infection in individuals with underly- Disseminated MAC has been well-described ing lung disease.1 in immunosuppressed patients. However, primary

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Immunocompetenta Patients With Primary Cutaneousb Mycobacterium avium Complex Infection Reported in the Literaturec

Case Age, Clinical Underlying Reference No. y Sex Distribution Appearance Condition Treatment

Schmidt 1 28 M Dorsal right Ulcer with History Isoniazid, et al19 foot erythematous of minor cycloserine, borders and abrasion to streptomycin yellow shaggy the affected base with area sinus tract formation

Lugo- 2 11 F Lateral right Ulcerated History of Unknown Janer foot with later plaques, trauma to et al13 dissemination draining the right foot to all extremi- sinuses, with fracture ties and erythematous of metatarsal infraorbital subcutaneous bones and area plaque and subsequent CUTISnodules osteomyelitis Ichiki 3 9 F Abdomen, 10 subcuta- Suspected Isoniazid, et al4 hips, thighs neous nodules, exogenous cycloserine, 2 ulcers inoculation clarithromycin, Do Not Copy excision

Escalonilla 4 57 M Wrist Nodule None Excision et al20

Nassar 5 43 F Right earlobe, Infiltrating None initially, Clarithromycin, et al10 progression to plaque but treated ethambutol, entire ear and progressing with oral rifabutin cheek to a nodular steroids, infiltrating thalidomide, lesion methotrexate, and infliximab for suspected sarcoidosis

Abbreviations: M, male; F, female. aPatients without conditions associated with impaired immunity (eg, human immunodeficiency virus/AIDS, diabetes mellitus) or conditions requiring treatment with systemic immunosuppressive therapy. bMycobacterium avium complex could not be isolated from a visceral, deep (hard or soft tissue), or hematogenous source. cNot included in this table are 3 reported cases of primary cutaneous Mycobacterium avium complex noted by Street et al21; nothing is known regarding these patients’ immune status. Furthermore, Nedorost et al12 reported a case of primary cutaneous infection in an immunocompetent host; however, the authors later found the patient to have bone involvement.

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cutaneous involvement without bacteremia remains refractory to treatment has proven favorable, if not relatively uncommon, even in immunocompromised definitive, in a few reported cases.4,5,14 patients, and is exceedingly rare in healthy indi- Despite the extensive literature on MAC, there is viduals.18 Schmidt et al19 presented the first case of a paucity of reports on primary cutaneous M avium in primary inoculation mycobacteriosis in an apparently healthy individuals. Primary cutaneous MAC, as with healthy individual. However, due to chest radiograph other cutaneous NTM infections, typically is second- abnormalities, the authors could not conclusively ary to trauma in immunocompetent hosts. The litera- rule out hematogenous spread from a primary pul- ture on cutaneous mycobacteriosis secondary to NTM monary focus.19 In the ensuing 38 years, according to other than MAC is extensive. Similar to our patient, a PubMed search of articles indexed for MEDLINE there has been a report of cutaneous MAC infection using the terms Mycobacterium avium complex and in a patient with a preceding history of gardening Mycobacterium avium-intracellulare, the English- and no explicit recollection of trauma to the affected language literature contains only 5 reports of primary area.15 Another patient was a farmer, implicating cutaneous MAC in nonimmunosuppressed patients soil and vegetation as a possible reservoir.7 However, (Table). Nassar et al10 reviewed a case in which an both of these patients were immunodeficient. Of the initially immunocompetent individual presented with remaining cases of healthy patients presented in the a nodular infiltrating lesion on the right cheek and Table, an uncertain history or suspicion of trauma is ear. When immunosuppressive therapy was initiated thought to be implicated in the cause of disease. Our for suspected sarcoidosis, the lesion extended to more case highlights how a seemingly innocuous substance, extensive areas of the cheek and the entire external even within the context of full immunocompetence, ear,10 which may attest to the predilection for dissemi- can be implicated in cutaneous disease. nated disease in immunocompromised patients. Accordingly, as more cases of cutaneous MAC in Of note, the Japanese literature has produced a healthy individuals are reported, a certain degree of large subset of pediatric cases in which healthy chil- suspicion must be maintained, particularly in patients dren have presented with multiple subcutaneous or who present with unresponsive lesions and a history ulcerating nodules. Prior to their own reported case, of possible trauma with environmental exposure. 4 CUTIS Ichiki et al noted 9 cases of primary cutaneous MAC As corroborated by prior cases, a misdiagnosis can in Japanese literature. indeed progress to more extensive skin involvement The treatment of MAC includes monotherapy and added morbidity for the patient. or combination therapy with a variety of antibiotics, along with possible excision.Do Although Not susceptibility REFERENCES Copy testing may be advantageous in cases of prior drug 1. Weitzul S, Eichhorn PJ, Pandya A. Nontuberculous exposure, clinical recurrence, or resistant disease, it mycobacterial infections of the skin. Dermatol Clin. has been suggested that MAC may be treated based 2000;18:359-377. on established sensitivity patterns. This same study 2. Friedman BF, Edwards D, Kirkpatrick CH. Mycobacterium recommended that in vitro sensitivity studies are in avium-intracellulare: cutaneous presentations of dissemi- fact only necessary for clarithromycin in patients pre- nated disease. Am J Med. 1988;85:257-263. viously exposed to macrolides.22 In their earlier review 3. Bartralot R, García-Patos V, Sitjas D, et al. Clinical pat- of the literature, Kakinuma and Suzuki5 concluded terns of cutaneous nontuberculous mycobacterial infec- that clarithromycin, minocycline, ciprofloxacin, and tions. Br J Dermatol. 2005;152:727-734. ansamycins individually or in various combinations 4. Ichiki Y, Hirose M, Akiyama T, et al. Skin infection are the best forms of antibiotic treatment; however, caused by Mycobacterium avium. Br J Dermatol. 1997;136: surgical excision is advocated when possible. In the 260-263. same report, the authors presented a case of primary 5. Kakinuma H, Suzuki H. 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9. Grice K. Sarcoidosis and Mycobacterium avium- 16. Cox SK, Strausbaugh LJ. Chronic cutaneous infection intracellulare cutaneous abscesses. Clin Exp Dermatol. caused by Mycobacterium intracellulare. Arch Dermatol. 1983;8:323-327. 1981;117:794-796. 10. Nassar D, Ortonne N, Grégoire-Krikorian B, et al. 17. Piketty C, Danic DL, Weiss L, et al. Sporotrichosislike Chronic granulomatous Mycobacterium avium skin pseudo- infection caused by Mycobacterium avium in the acquired tumour. Lancet Infec Dis. 2009;9:136. immunodeficiency syndrome. Arch Dermatol. 1993;129: 11. Mattila JO, Vornanen M, Vaara J, et al. Mycobacteria in 1343-1344. prurigo nodulares: the cause or a consequence? J Am Acad 18. Inwald D, Nelson M, Cramp M, et al. Cutaneous manifes- Dermatol. 1996;34(2, pt 1):224-228. tations of mycobacterial infection in patients with AIDS. 12. Nedorost ST, Elewski B, Tomford JW, et al. Rosacea-like Br J Dermatol. 1994;130:111-114. lesions due to familial Mycobacterium avium-intracellulare 19. Schmidt JD, Yeager H Jr, Smith EB, et al. Cutaneous infec- infection. Int J Dermatol. 1991;30:491-497. tion due to a Runyon group 3 atypical Mycobacterium. Am 13. Lugo-Janer G, Cruz A, Sánchez JL. Disseminated cutane- Rev Respir Dis. 1972;106:469-471. ous infection caused by Mycobacterium avium complex. 20. Escalonilla P, Esteban J, Soriano ML, et al. Cutaneous Arch Dermatol. 1990;126:1108-1110. manifestations of infection by nontuberculous mycobacte- 14. Barbaro DJ, Orcutt VL, Coldiron BM. Mycobacterium ria. Clin Exp Dermatol. 1998;23:214-221. avium-Mycobacterium intracellulare infection limited to the 21. Street ML, Umbert-Millet IJ, Roberts GD, et al. Nontu- skin and lymph nodes in patients with AIDS. Rev Infect berculous mycobacterial infections of the skin. report of Dis. 1989;11:625-628. fourteen cases and review of the literature. J Am Acad 15. Kayal JD, McCall CO. Sporotrichoid cutaneous Dermatol. 1991;24(2, pt 1):208-215. Mycobacterium avium complex infection. J Am Acad 22. Petrini B. Non-tuberculous mycobacterial infections. Dermatol. 2002;47(suppl 5):S249-S250. Scand J Infect Dis. 2006;38:246-255. CUTIS Do Not Copy

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