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There Must Be Something in the Water: An Unusual Cutaneous Infection

      Presentation

      A 77-year-old man presented to the emergency department with a 6-week history of a nonhealing violaceous nodular plaque on the dorsum of his right hand after he sustained a minor puncture injury on the side of a boat while sailing on the Chesapeake Bay. His past medical history was significant for heart failure with preserved ejection fraction, chronic kidney disease stage 3, coronary artery disease, aortic stenosis, and gout. Given lack of healing over the subsequent weeks, he twice sought care at local urgent care centers without response to cephalexin and later clindamycin. He denied a history of fevers, night sweats, or weight loss. Exposure history was relevant for his boating injury as well as a hobby of gardening, including rose bushes. He had no known immunocompromising condition. Due to ongoing progressive pain, erythema extending up the medial forearm, and new subcutaneous nodules on the forearm, he presented to the emergency department.

      Assessment

      On admission, he was normotensive, without tachycardia, and afebrile. Physical examination revealed an erythematous to violaceous ulcerated nodular plaque (Figure 1). There were few subcutaneous nontender palpable nodules tracking up the medial forearm (Figure 2). Initial investigations included a white blood cell count of 6.23 × 109/L, an erythrocyte sedimentation rate (ESR) of 11 mm/h, and a C-reactive protein of <0.3 mg/L. A right-hand X-ray revealed soft tissue swelling without osseous abnormality.
      Figure 1
      Figure 1A violaceous and ulcerated plaque on the dorsal surface of the right hand.
      Figure 2
      Figure 2Numerous subcutaneous nontender palpable nodules tracking up the medial right forearm.
      A wide differential diagnosis was considered for this presentation of a subacute, progressive, nonhealing, ulcerative, violaceous lesion with ascending nodular lymphangitis. Infectious processes considered in light of the appearance included atypical mycobacterial disease, sporotrichosis, endemic mycoses including histoplasmosis, lymphocutaneous nocardiosis due to Nocardia Brasiliensis, tularemia, erysipeloid, cutaneous anthrax, cutaneous leishmaniasis, and aspergillosis.
      • Smego Jr, RA
      • Castiglia M
      • Asperilla MO
      Lymphocutaneous syndrome. A review of non-sporothrix causes.
      ,
      • Giordano CN
      • Kalb RE
      • Brass C
      • Lin L
      • Helm TN
      Nodular lymphangitis: report of a case with presentation of a diagnostic paradigm.
      Noninfectious causes were also considered including pyoderma gangrenosum and cutaneous lymphoma. Subacute time course and appearance did not favor typical bacterial pathogens responsible for nonsuppurative cellulitis. Mycobacterium marinum and sporotrichosis were ultimately favored based on exposure history to saltwater and rose gardening.

      Diagnosis

      Dermatology was consulted for skin biopsy with pathology and bacterial, fungal, and mycobacterial tissue culture. In the interim, blood cultures were no growth and T-spot testing was positive. Punch biopsy noted mixed inflammatory cells filling the dermis, including large numbers of histiocytes consistent with a granulomatous dermatitis (Figure 3). Acid-fast bacillus (AFB) staining highlighted mycobacterial organisms within the dermis (Figure 4). Mycobacterial cultures ultimately speciated as M. marinum.
      Figure 3
      Figure 3Punch biopsy of the right dorsal hand lesion with mixed inflammatory cells filling the dermis, including large numbers of histiocytes consistent with a granulomatous dermatitis.
      Figure 4
      Figure 4AFB staining with mycobacterial organisms within the dermis. AFB = acid-fast bacillus.

      Management

      Because the AFB tissue stain was positive, empiric treatment for nontuberculous mycobacterial skin and soft tissue infection was initiated with clarithromycin 500 mg twice daily, ethambutol 15 mg/kg daily, and trimethoprim-sulfamethoxazole 160-800 mg twice daily. On follow up in the infectious disease clinic, trimethoprim-sulfamethoxazole was stopped, and he was treated with a 6-month course of therapy with ethambutol and clarithromycin with ongoing resolution of the skin lesions.

      Discussion

      Nontuberculous mycobacteria are a miscellaneous collection of acid-fast bacteria other than Mycobacterium tuberculosis complex or Mycobacterium leprae that are widespread in the environment and are known to cause skin and soft tissue infections in humans.
      • Daley CL
      • Iaccarino JM
      • Lange C
      • et al.
      Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA Clinical Practice Guideline.
      Though more than 190 species of nontuberculous mycobacteria have been identified, not all have been implicated in human disease.
      • Daley CL
      • Iaccarino JM
      • Lange C
      • et al.
      Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA Clinical Practice Guideline.
      Common environmental sources of nontuberculous mycobacteria include water, soil, plants, and animals.
      • Wang SH
      • Pancholi P.
      Mycobacterial skin and soft tissue infection.
      The pathogenesis of cutaneous mycobacterial infection is most often direct inoculation into the skin and soft tissues.
      • Bartralot R
      • García-Patos V
      • Sitjas D
      • et al.
      Clinical patterns of cutaneous nontuberculous mycobacterial infections.
      Fresh or saltwater injuries are a common source of infection, including secondary to slow growing nontuberculous mycobacteria such as M. marinum.
      • Franco-Paredes C
      • Marcos LA
      • Henao-Martínez AF
      • et al.
      Cutaneous mycobacterial infections.
      Rapidly growing mycobacteria such as Mycobacterium fortuitum, Mycobacterium abscessus, and Mycobacterium chelonae are common causes of community-acquired skin and soft tissue infections in the United States and have been shown to be inoculated secondary to trauma associated with surgery, cosmetic procedures, acupuncture, tattoos, skin piercings, and nail salons.
      • Franco-Paredes C
      • Marcos LA
      • Henao-Martínez AF
      • et al.
      Cutaneous mycobacterial infections.
      • Chirasuthat P
      • Triyangkulsri K
      • Rutnin S
      • Chanprapaph K
      • Vachiramon V
      Cutaneous nontuberculous mycobacterial infection in Thailand: a 7-year retrospective review.
      • Griffin I
      • Schmitz A
      • Oliver C
      • et al.
      Outbreak of tattoo-associated nontuberculous mycobacterial skin infections.
      Immunocompromised patients such as those with advanced HIV/AIDS may present with cutaneous manifestations from disseminated mycobacterial infection including secondary to Mycobacteria avium complex, Mycobacterium kansasii, Mycobacterium genavense, and Mycobacterium haemophilum.
      • Wi YM
      Treatment of extrapulmonary nontuberculous mycobacterial diseases.
      One should suspect cutaneous nontuberculous mycobacteria infection when a patient presents with a solitary and slowly growing papule or nodule at a site of trauma that then progresses to a verrucous, violaceous plaque or ulcerates.
      • Bartralot R
      • García-Patos V
      • Sitjas D
      • et al.
      Clinical patterns of cutaneous nontuberculous mycobacterial infections.
      ,
      • Dodiuk-Gad R
      • Dyachenko P
      • Ziv M
      • et al.
      Nontuberculous mycobacterial infections of the skin: A retrospective study of 25 cases.
      Sporotrichoid distribution from proximal extension through lymphangitic spread may occur.
      • Franco-Paredes C
      • Marcos LA
      • Henao-Martínez AF
      • et al.
      Cutaneous mycobacterial infections.
      ,
      • Dodiuk-Gad R
      • Dyachenko P
      • Ziv M
      • et al.
      Nontuberculous mycobacterial infections of the skin: A retrospective study of 25 cases.
      ,
      • Faccini-Martinez AA
      • Zanotti RL
      • Moraes MS
      • Falqueto A
      Nodular lymphangitis syndrome.
      In contrast to pyogenic infections, cutaneous nontuberculous mycobacteria disease is often less painful or painless, typically lacks signs of systemic inflammation or locoregional lymphadenopathy, and the incubation period is prolonged with an average of approximately 2 to 4 weeks and can be as long as 9 months.
      • Jernigan JA
      • Farr BM
      Incubation period and sources of exposure for cutaneous Mycobacterium marinum infection: case report and review of the literature.
      ,
      • Piersimoni C
      • Scarparo C
      Extrapulmonary infections associated with nontuberculous mycobacteria in immunocompetent persons.
      Complications of cutaneous nontuberculous mycobacteria disease include extension to deeper tissues resulting in myositis, tenosynovitis, or osteomyelitis.
      • Franco-Paredes C
      • Marcos LA
      • Henao-Martínez AF
      • et al.
      Cutaneous mycobacterial infections.
      Definitive diagnosis requires isolation of nontuberculous mycobacteria in culture of biopsy, drainage, or aspirate of fluid from a skin lesion.
      • Piersimoni C
      • Scarparo C
      Extrapulmonary infections associated with nontuberculous mycobacteria in immunocompetent persons.
      M. marinum is a slow-growing pigmented organism that causes cutaneous infection most frequently from trauma in freshwater or saltwater, including puncture injuries associated with natural bodies of water, aquariums, shellfish, and swimming pools.
      • Jernigan JA
      • Farr BM
      Incubation period and sources of exposure for cutaneous Mycobacterium marinum infection: case report and review of the literature.
      Cutaneous lesions are most frequently in the extremities due to its optimal temperature for growth of 30°C.
      • Franco-Paredes C
      • Marcos LA
      • Henao-Martínez AF
      • et al.
      Cutaneous mycobacterial infections.
      Deep tissue involvement may occur in all hosts though more commonly in severely immunocompromised patients.
      • Franco-Paredes C
      • Marcos LA
      • Henao-Martínez AF
      • et al.
      Cutaneous mycobacterial infections.
      Similarly systemic dissemination is rare due to poor growth at core body temperature, though has been reported in the immunocompromised.
      • Wang SH
      • Pancholi P.
      Mycobacterial skin and soft tissue infection.
      Diagnosis may be challenging both because of the lack of recognition of characteristic features of this syndrome and a high percentage of tissue samples negative for AFB by staining or granulomatous inflammation by histopathology. In one case series of 28 patients with confirmed M. marinum infection by tissue culture, only 58 percent of tissue biopsies noted granulomatous inflammation with only 11 percent positive with AFB staining.
      • Johnson MG
      • Stout JE
      Twenty-eight cases of Mycobacterium marinum infection: retrospective case series and literature review.
      Treatment often involves a combination of at least 2 drugs, including a macrolide, trimethoprim-sulfamethoxazole, rifamycin, or ethambutol with duration ranging from 2 to 6 months depending on the extent of involvement and response to therapy.
      • Franco-Paredes C
      • Marcos LA
      • Henao-Martínez AF
      • et al.
      Cutaneous mycobacterial infections.
      ,
      • Johnson MG
      • Stout JE
      Twenty-eight cases of Mycobacterium marinum infection: retrospective case series and literature review.
      In this article, we present a case of an elderly immunocompetent gentleman who sustained a waterborne injury with a resultant subacute development of nodular skin lesion that progressed into a violaceous plaque with ulceration and nodular lymphangitic spread not responsive to typical antistaphylococcal and antistreptococcal antibiotics. This case illustrates the importance of detailed history taking and recognizing cutaneous M, marinum on the differential for skin and soft tissue infections, particularly with characteristic examination features, indolent progression, antibiotic failure, or history of penetrating injury with water exposure.

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