Le Infezioni in Medicina, n. 2, 285-292, 2022

doi: 10.53854/liim-3002-15

CASE REPORT

Uncommon lymphocutaneous cellulitis after insect bite: a case report of primary cutaneous nocardiosis and literature review

Antonio Lovecchio1, Giulia Bazzacco2, Stefano Di Bella3, Nicola Di Meo2, Roberto Luzzati3

1Infectious Diseases Unit, Trieste University Hospital, Trieste, Italy;

2Dermatology and Venereology Department, Dermatology Clinic, University of Trieste, Trieste, Italy;

3Clinical Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy

Article received 31 March 2022, accepted 3 May 2022

Corresponding author

Antonio Lovecchio

E-mail: antonio.lovecchio@asugi.sanita.fvg.it

SummaRY

Nocardia is a genus of aerobic actinomycetes that are usually responsible for opportunistic infection in immunocompromised patients. Less frequently nocardiosis can interest immunocompetent population, causing especially primary cutaneous infections. Cutaneous involvement by Nocardia spp. may occur mostly as one of four clinical manifestations: superficial cellulitis or abscess, mycetoma, lymphocutaneous (also defined “sporotrichoid”) infection and secondary cutaneous involvement from systemic disease. Infections usually present after minor local injury, especially in traumatic outdoor activities (e.g. gardeners, farmers, road accidents), with subsequent environmental contamination of the wound. In sporadic cases cutaneous infection follows an insect bite. Microbiological diagnosis is often difficult to obtain and N. brasiliensis is the species isolated in most cases (80%). We present the case of a 45-year-old female with fever and a painful and necrotizing lesion on her right leg with secondary ascending lesions occurred on the homolateral knee and consensual groin lymphadenopathy after insect sting (maybe a spider bite). Cultures on skin biopsy identified Nocardia brasiliensis. Infection was completely healed after 5 months of targeted antibiotic therapy. In addition, we performed a literature review of all cutaneous nocardiosis cases in immunocompetent individuals, finding that only in 22 cases the infection presented after insect bite; in most of these cases lymphocutaneous manifestation was seen and N. brasiliensis was the Nocardia species isolated. Our case, along with others in literature, reveals that the real burden of soft-tissues nocardiosis seems low but probably many cases might go undiagnosed because of difficulties in microbiology diagnosis. Primary cutaneous nocardiosis should be included in the diagnostic pathway in cases of cellulitis following insect bite or sting, especially when localized to extremities.

Keywords: nocardia, cutaneous nocardiosis, actinomycetes, insect bite, immunocompetent.

INTRODUCTION

Nocardia is a genus of aerobic actinomycetes which turns out to be a weakly Gram-positive and acid-fast bacterium. Unlike other Gram-positive bacteria, Nocardia spp. appear as filamentous bacteria with hyphae-like branching on direct microscopy [1]. Nocardia is usually an opportunistic pathogen and most infections occur in immunocompromised patients. In particular, patients with depressed cell-mediated immunity (e.g. HIV/AIDS, solid-organ transplanted patients, etc.) have a higher risk of nocardiosis. However, up to one-third of patients with nocardiosis are immunocompetent [1]. Clinical manifestations of nocardiosis include pulmonary disease, central nervous system (CNS) infections, systemic and primary cutaneous nocardiosis. Unlike other forms of nocardiosis, primary cutaneous nocardiosis develops more commonly in immunocompetent patients. Cutaneous involvement by Nocardia spp. may occur as several clinical manifestations: more frequently superficial cellulitis or abscess, mycetoma, lymphocutaneous (also defined “sporotrichoid”) infection and secondary cutaneous involvement from systemic disease are seen [2]. However, presentation as pustules or nodules, granulomas, ulcerative, necrotic or keloid-like lesions and other non-specific cutaneous clinical lesion can be seen.

CASE PRESENTATION

We present the case of a 45-year-old female who presented to the emergency department complaining for fever and a painful and purplish lesion surrounded by erythema on her right leg. The patient reported an insect sting (maybe a spider bite) on her right leg while she was working in her garden three days prior to the admission. Her past medical history included oophorectomy for a previous ovarian cancer and Helicobacter pylori-related gastritis.

On clinical examination, she was febrile (max 38.6°C) and there was a black-purplish lesion surrounded by an erythematous halo on the right leg at the site of the insect bite (Figure 1, a), associated with cutaneous erythema. This necrotizing lesion showed in 48 hours a central ulcerative evolution and the erythematous halo expanded towards the periphery (Figure 1, b). Within the following 3 days, secondary ascending lesions occurred with swelling erythema of the homolateral knee and groin lymphadenopathy (Figure 1, c). Laboratory examinations showed increased values of C-reactive protein (25 mg/L, normal value <5 mg/L) and white blood cell count (14x103/mm3).

The patient was then admitted to the Infectious Diseases Unit. In the meantime, a primary diagnosis of cellulitis was made, and intravenous therapy with amoxicillin/clavulanate (2.2 g intravenously every 6 hours) and clindamycin (900 mg intravenously every 8 hours) were commenced. Blood cultures yielded negative results. Since no improvement was observed, after 48 hours doxycycline (100 mg every 12 hours) was added to the regimen for empirical clindamycin-resistant S. aureus coverage. Clindamycin was continued for its anti-toxin effect. Despite antibiotic therapy, the patient remained feverish, the erythema continued to spread, and the black-purplish lesion kept expanding and necrotizing; C-reactive protein increased up to 160 mg/L. A computed tomography (CT)-scan of the leg showed images consistent with fasciitis of lateral face of thigh and leg, subcutaneous tissues swelling, and consensual enlarging inguinal lymphadenopathy.

Samples for microbiological examination were collected by lesion biopsy. After 7 days of empirical therapy, culture turned out positive for weakly Gram-positive and acid-fast actinomycetes, identified as Nocardia brasiliensis. Susceptibility tests (CLSI breakpoints) showed resistance to ciprofloxacin (MIC 4), clarithromycin (MIC >16) and tetracyclines (doxycycline MIC 4; minocycline MIC 2), while susceptibility was maintained toward trimethoprim-sulfamethoxazole (TMP-SMX MIC <=0.25), linezolid (MIC <=1) and beta-lactams (amoxicillin/clavulanate MIC <=2). Therefore, parenteral antibacterial therapy with intravenous linezolid (600 mg every 12 hours) and intravenous TMP-SMX (240/1200 mg every 8 hours) was started with subsequent improvement of signs and symptoms and decreasing inflammatory markers with resolution of fever and progressive reduction of erythema and lesions’ size. Combination therapy was chosen according to the severity of the case and fascia involvement.

TMP-SMX was interrupted after 5 days for onset of cutaneous rash. Patient was discharged from the hospital after 10 days of parenteral therapy with indication to receive oral therapy with amoxicillin/clavulanate (1 g every 8 hours) and linezolid (600 mg every 12 hours). Three weeks later linezolid was interrupted for anemia, while amoxicillin/clavulanate was prolonged for a total of 5 months. During the follow-up, cellulitis was completely healed with only a few dyschromic scars left (Figure 1, d).

Figure 1 - Evolution of the tibial lesion at site of the insect bite (a, b); secondary ascending lesions (c) and outcome after treatment (d).

LITERATURE REVIEW

We performed a literature review of cutaneous nocardiosis cases in immunocompetent population. On January 2022 we performed a PubMed search using the following search strings: “Cutaneous” AND “Nocardiosis”. 487 papers regarding such topic were identified. Among them, we selected, by abstract or full text reading, 95 articles (case reports and case series) on primary cutaneous nocardiosis in immunocompetent patients. We excluded any article that didn’t include at least one case report and cases of infections caused by other pathogens. Furthermore, we excluded cases of non-cutaneous nocardiosis, secondary lesions or disseminated disease and cutaneous nocardiosis in immunocompromised patients (congenital immunodeficiency, HIV infection, hematological diseases, solid tumor or other acquired immunodeficiency) or patients using immunosuppressing drugs (e.g. chemotherapy, long-term steroid therapy, biologic drugs or other immunosuppressor drugs) (Figure 2). As a result, most cases of cutaneous nocardiosis in immunocompetent patients resulted to involve the extremities (arm, hand, or leg) and occurred following a minor trauma, especially during gardening or agriculture work. No differences in severity were observed in immunocompetent patients between infections caused by different Nocardia species, considering that only sporadic cases were determined by species different from N. brasiliensis. In fact, N. brasiliensis and N. asteroides were the most frequent Nocardia species isolated (respectively 60% and 10%), in most cases identified by 16s rRNA gene amplification and sequencing laboratory tests (Supplementary Table). N. brasiliensis turned out to be more frequently responsible for lymphatic extension of the infection and infections caused by this species were often complicated by abscess formation. More often a chronic presentation was observed and only in few cases there was a rapid progression of disease after primary lesion. Only 10 articles reported episodes of cutaneous or lymphocutaneous nocardiosis as a consequence of an insect bite: 1 from tick bite, 1 after wasp sting, 1 after spider bite and in the other 19 cases the insects were not identified. In all these cases N. brasiliensis was isolated from cutaneous samples (Table 1).

Figure 2 - Flowchart of literature review by searching “cutaneous” and “nocardiosis” on PubMed.

DISCUSSION

Primary cutaneous nocardiosis affects more commonly immunocompetent hosts and N. brasiliensis is the species isolated in most cases (80%) [2]. Primary cutaneous infections include lymphocutaneous infection, superficial cellulitis, or localized abscess, and usually involve the face in children and the lower extremities in adults. In an immunocompetent individual, they occur 1 to 3 weeks following minor local injury, especially in traumatic outdoor activities (e.g. gardeners, farmers, road accidents), with subsequent environmental contamination of the wound [2]. Exceptionally, the infection presents after an insect bite or sting. Clinical signs usually have a slow progression, in weeks or months. Interestingly, in our case a very fast and extensive progression of ascending cellulitis was seen, with the appearance in 3 days of secondary cutaneous lesions and regional lymph-nodes involvement. Indeed, in our case the diagnosis of cutaneous nocardiosis was delayed because it was clinically indistinguishable from skin infections caused by other organisms, such as common pyogenic bacteria, fungi or atypical mycobacteria, as reported in other series. The preferred diagnostic specimen for cutaneous nocardiosis is obtained by skin biopsy. The microbiological diagnosis of these actinomycetes can be challenging because of their slow growth that can take up to 14 days on solid media (laboratory should be informed of the diagnostic suspect and samples should be incubated up to 2 weeks). Indeed, Nocardia may grow on most routine media and blood culture bottles, but specific media can be used to increase sensitivity (e.g. buffered charcoal yeast extract). Furthermore, these organisms can be hypothesized obtaining Gram staining, Gomori methenamine silver stain or modified Kinyoun acid-fast staining. The choice and dosage of antimicrobial drugs and the duration of therapy depend on the site and the extent of infection, underlying host factors, the species of Nocardia, and the clinical response to initial management. As clinical isolates of Nocardia spp. show variable susceptibility to antimicrobials, antimicrobial susceptibility testing should always be performed. TMP-SMX is the cornerstone of nocardiosis therapy, and its total duration should be 3-6 months, but shorter courses may be appropriate in immunocompetent patients [96]. Intravenous multidrug regimen can be used for initial treatment and should be continued for at least 2-6 weeks. Debridement of infected tissues, and incision and drainage of abscesses are often necessary; deep locations may require consultation for interventional radiology-guided evacuation. In our case, antibiotic therapy was continued for 5 months because of infection severity, fascia’s involvement, and lack of surgical approach.

In conclusion, primary cutaneous nocardiosis usually develops in immunocompetent host. N. brasiliensis is the most common species causing cutaneous or lymphocutaneous disease, as in our case. The real burden of soft-tissues nocardiosis seems low but many cases might go undiagnosed because of difficulties in microbiology diagnosis. Our case suggests that primary cutaneous nocardiosis should be included in the diagnostic pathway in cases of cellulitis following insect bite or sting, especially when localized to extremities.

Conflict of interest

None of the authors have conflict of interest.

Funding

No funding was received for the preparation of the manuscript.

Ethical declaration

The patient gave her written and informed consent for publishing case description and pictures. Authors made every attempt to guarantee the patient’s anonymity.

REFERENCES

[1] Wilson JW. Nocardiosis: updates and clinical overview. Mayo Clin Proc. 2012; 87 (4), 403-7.

[2] Brown-Elliott BA, Brown JM, Conville PS, Wallace RJ. Clinical and Laboratory Features of the Nocardia spp. Based on Current Molecular Taxonomy. Clin Microbiol Rev. 2006; 19 (2), 259-82.

[3] Leggiadro RJ, Miller RB. Cutaneous nocardiosis presenting as a tick-borne infection. Pediatr Infect Dis J. 1987; 6 (4), 421-2.

[4] O’Connor PT, Dire DJ. Cutaneous nocardiosis associated with insect bites. Cutis. 1992; 50 (4), 301-2.

[5] Paredes BE, Hunger RE, Braathen LR, Brand CU. Cutaneous Nocardiosis Caused by Nocardia brasiliensis after an Insect Bite. Dermatology. 1999; 198 (2), 159-61.

[6] Slevogt H, Schiller R, Wesselmann H, Suttorp N. Ascending cellulitis after an insect bite. Lancet. 2001; 357 (9258), 768.

[7] Fergie JE, Purcell K. Nocardiosis in South Texas children. Pediatr Infect Dis J. 2001; 20 (7), 711-4.

[8] Isbister GK, Whyte IM. Suspected white-tail spider bite and necrotic ulcers. Intern Med J. 2004; 34 (1-2), 38-44.

[9] Secchin P, Trope BM, Fernandes LA, Barreiros G, Ramos-e-Silva M. Cutaneous Nocardiosis Simulating Cutaneous Lymphatic Sporotrichosis. Case Rep Dermatol. 2017; 9 (2), 119-29.

[10] Chu L, Xu X, Ran Y. Primary cutaneous nocardiosis caused by Nocardia brasiliensis following a wasp sting. Clin Exp Dermatol. 2017; 42 (4), 416-9.

[11] Mu Y, Liu Y, Wang Y, Zhang Z. A case report and review of lymphocutaneous nocardiosis caused by Nocardia brasiliensis reported in China. Dermatol Ther. 2019; 32, e13001.

[12] Acevedo CT, Imkamp F, Marques Maggio E, Brugger SD. Primary cutaneous nocardiosis of the head and neck in an immunocompetent patient. BMJ Case Rep. 2021; 14 (5), e241217.

[13] Vasarinsh P. Primary cutaneous nocardiosis. Arch Dermatol. 1968; 98 (5), 489-93.

[14] Satterwhite TK. Primary Cutaneous Nocardiosis. JAMA. 1979; 242 (4), 333.

[15] Kahn FW, Gornick CC, Tofte RW. Primary cutaneous Nocardia asteroides infection with dissemination. Am J Med. 1981; 70 (4), 859-63.

[16] Kalb RE, Kaplan MH, Grossman ME. Cutaneous nocardiosis. Case reports and review. J Am Acad Dermatol. 1985; 13 (1), 125-33.

[17] Smeal W, Schenfeld LA. Nocardiosis in the community hospital. Postgrad Med. 1986; 79 (8), 77-82.

[18] Girouard Y, Albert G, Thivierge B, Lorange-Rodrigues M. Primary cutaneous nocardiosis due to Nocardia caviae. CMAJ. 1987; 136 (8), 844-5.

[19] Hironaga M, Mochizuki T, Watanabe S. Acute primary cutaneous nocardiosis. J Am Acad Dermatol. 1990; 23 (2), 399-400.

[20] Hiruma M, Kawada A, Ishibashi A, Mikami Y. Localized cutaneous nocardiosis in Japan. A new case. Mycopathologia. 1992; 117 (3), 133-8.

[21] Harth Y, Friedman-Birnbaum R, Lefler E, Bergman R. Two patients with simultaneous, unusually located primary cutaneous nocardiosis. J Am Acad Dermatol. 1992; 26 (1), 132-3.

[22] Georghiou PR, Blacklock ZM. Infection with Nocardia species in Queensland. A review of 102 clinical isolates. Med J Aust. 1992; 156 (10), 692-7.

[23] Schiff TA, McNeil MM, Brown JM. Cutaneous Nocardia farcinica infection in a nonimmunocompromised patient: case report and review. Clin Infect Dis. 1993; 16 (6), 756-60.

[24] Saff DM, Poulos EG, Unis ME. Ulcerative lesions in a gardener. Cutaneous nocardiosis. Arch Dermatol. 1994; 130 (2), 243-46.

[25] Clark NM, Braun DK, Pasternak A, Chenoweth CE. Primary cutaneous Nocardia otitidiscaviarum infection: case report and review. Clin Infect Dis. 1995; 20 (5), 1266-70.

[26] Ingole K, Fule RP, Jalgaonkar S v. Primary cutaneous disease due to Nocardia asteroides-a case report. Indian J Med Sci. 1995; 49 (10), 231-2.

[27] Kannon GA, Kuechle MK, Garrett AB. Superficial cutaneous Nocardia asteroides infection in an immunocompetent pregnant woman. J Am Acad Dermatol. 1996; 35 (6), 1000-2.

[28] Karakayali G, Karaarslan A, Artuz F, Alli N, Tekeli A. Primary cutaneous Nocardia asteroides. Br J Dermatol. 1998; 139 (5), 919-20.

[29] Bhalodia AM, Lertzman BH, Kantor GR, Granick MS. Localized cutaneous Nocardia brasiliensis mimicking foreign body granuloma. Cutis. 1998; 61 (3), 161-3.

[30] Camozzota C, Goldman A, Tchernev G, Lotti T, Wollina U. A Primary Cutaneous Nocardiosis of the Hand. Open Access Maced J Med Sci. 2017; 5 (4), 470-2.

[31] Angelika J, Hans-Jürgen G, Uwe-Frithjof H. Primary cutaneous nocardiosis in a husband and wife. J Am Acad Dermatol. 1999; 41 (2), 338-40.

[32] Flores González L, Carballo MG, Muñoz E, Dionisio de Cabalier ME. Localized nocardiosis. Rev Fac Cien Med Univ Nac Cordoba. 1999; 56 (2), 105-11.

[33] Hornef MW, Gandorfer A, Heesemann J, Roggenkamp A. Humoral response in a patient with cutaneous nocardiosis. Dermatology. 2000; 200 (1), 78-80.

[34] Comellas J, Morales M, Granell F. Nodular lymphangitis caused by Nocardia asteroides. Enferm Infecc Microbiol Clin. 2000; 18 (8), 385-8.

[35] Z’Graggen WJ, Bregenzer T, Fankhauser H, Arnoux A, Laeng H, Itin PH. Primary cutaneous nocardiosis in an immune-competent patient. Eur J Dermatol. 2001; 11 (6), 569-71.

[36] Aydingöz IE, Candan I, Dervent B, Hitit G. Primary cutaneous nocardiosis associated with intra-articular corticosteroid injection. Int J Dermatol. 2001; 40 (3), 196-8.

[37] Shimizu A, Ishikawa O, Nagai Y, Mikami Y, Nishimura K. Primary cutaneous nocardiosis due to Nocardia nova in a healthy woman. Br J Dermatol. 2001; 145 (1), 154-6.

[38] Astudillo L, Dahan S, Escourrou G, et al. Cat scratch responsible for primary cutaneous Nocardia asteroides in an immunocompetent patient. Br J Dermatol. 2001; 145 (4), 684-5.

[39] Wang AW, D’Cruz M, Leung M. Primary cutaneous nocardiosis of the hand: a case report and literature review. Hand Surg. 2002; 7 (1), 155-7.

[40] Gyotoku T, Kayashima K, Nishimoto K, Ono T. Cutaneous Nocardiosis Developing around Gravel Inserted during a Traffic Injury. Dermatol J. 2002; 29 (12), 803-9.

[41] Inamadar AC, Palit A. Primary cutaneous nocardiosis: a case study and review. Indian J Dermatol Venereol Leprol. 2003; 69 (6), 386-91.

[42] Maraki S, Scoulica E, Alpantaki K, Dialynas M, Tselentis Y. Lymphocutaneous nocardiosis due to Nocardia brasiliensis. Diagn Microbiol Infect Dis. 2003; 47 (1), 341-4.

[43] Lum CA, Vadmal MS. Case report: Nocardia asteroides mycetoma. Ann Clin Lab Sci. 2003; 33 (3), 329-33.

[44] Maraki S, Chochlidakis S, Nioti E, Tselentis Y. Primary lymphocutaneous nocardiosis in an immunocompetent patient. Ann Clin Microbiol Antimicrob. 2004; 3, 24.

[45] Ogasawara Y, Takita Y, Hiruma M, Mikami Y, Muto M. Primary cutaneous nocardiosis due to Nocardia brasiliensis in an immunocompetent patient. J Dermatol. 2005; 32 (3), 230-2.

[46] Kil EH, Tsai CL, Kwark EH, Goldwasser J. A case of nocardiosis with an uncharacteristically long incubation period. Cutis. 2005; 76 (1), 33-6.

[47] Stefano PC, Noriega AL, Kobrin AL, et al. Primary cutaneous nocardiosis in immunocompetent children. Eur J Dermatol. 2006; 16 (4), 406-8.

[48] Thoms K-M, Zimmermann O, Schupp P, Thoms S, Emmert S. Nocardia otitidiscaviarum: cause of long-term cutaneous abscesses on the leg of an immunocompetent man. Arch Dermatol. 2007; 143 (8), 1086-7.

[49] Fukuda H, Saotome A, Usami N, Urushibata O, Mukai H. Lymphocutaneous type of nocardiosis caused by Nocardia brasiliensis: a case report and review of primary cutaneous nocardiosis caused by N. brasiliensis reported in Japan. J Dermatol. 2008; 35 (6), 346-53.

[50] Baradkar VP, Mathur M, Kulkarni SD, Kumar S. Sporotrichoid pattern of cutaneous nocardiasis due to Nocardia asteroids. Indian J Pathol Microbiol. 2008; 51 (3), 432-4.

[51] Pardo M, Bonifaz A, Valencia A, Araiza J, Mejia SA, Mena-Cedillos C. Actinomycetoma by Nocardia brasiliensis in a girl with Down syndrome. Dermatol Online J. 2008; 14 (8), 9.

[52] Dodiuk-Gad R, Cohen E, Ziv M, et al. Cutaneous nocardiosis: report of two cases and review of the literature. Int J Dermatol. 2010; 49 (12), 1380-5.

[53] Lohmeyer JA, Machens H-G, Werber K-D. A case of severe cutaneous nocardiosis. J Hand Surg Eur Vol. 2010; 35 (1), 72-3.

[54] Bosamiya SS, Vaishnani JB, Momin AM. Sporotrichoid nocardiosis with cutaneous dissemination. Indian J Dermatol Venereol Leprol. 2011; 77 (4), 535.

[55] Kim MS, Choi H, Choi KC, Shin BS. Primary cutaneous nocardiosis due to Nocardia vinacea: first case in an immunocompetent patient. Clin Exp Dermatol. 2011; 36 (7), 812-4.

[56] Praveen Kumar S, Sumathy TK, Shyam Prasad AL, Gayathri Devi DR, Shivaswamy KN, Ranganathan C. An unusual presentation of primary cutaneous nocardiosis at a rare site: succesful treatment with a modified Welsh regimen. Dermatol Online J. 2011; 17 (12), 1.

[57] Soma S, Saha P, Sengupta M. Cutaneous Nocardia brasiliensis infection in an immunocompetent host after ovarian cystectomy: A case study. Australas Med J. 2011; 4 (11), 603-5.

[58] Agrawal SM, Raut SS. Primary cutaneous disease due to Nocardia asteroides in an immunocompetent host. Indian J Pathol Microbiol. 2011; 54 (1), 185-6.

[59] Saoji VA, Saoji S v, Gadegone RW, Menghani PR. Primary cutaneous nocardiosis. Indian J Dermatol. 2012; 57 (5), 404-6.

[60] Jiménez-Gallo D, Albarrán-Planelles C, Galán-Sánchez F, Linares-Barrios M, Girón-González JA. Primary cutaneous nocardiosis caused by Nocardia farcinica. Rev clin esp. 2012; 212 (7), e49-51.

[61] Derancourt C, Theodose R, Deschamps L, et al. Primary cutaneous nocardiosis caused by Nocardia beijingensis. Br J Dermatol. 2012; 167 (1), 216-8.

[62] Shachor-Meyouhas Y, Ravid S, Suhair H, Kassis I. Primary cutaneous Nocardia brasiliensis cellulitis in immunocompetent child. Harefuah. 2012; 151 (8), 476-8, 497, 496.

[63] Antunes J, Pacheco D, Travassos R, Sequeira H, Filipe P, Marques MS. Actinomycetoma of the chest wall attributed to Nocardia nova after reconstructive surgery. Dermatol Online J. 2012; 18 (1), 4.

[64] Pai S, Pai K, Sharma S. Cutaneous nocardiosis: an underdiagnosed pathogenic infection. BMJ Case Rep. 2015. doi: 10.1136/bcr-2014-208713 Last accessed April 22, 2022.

[65] Iketani Y, Hata Y, Yamamoto N, Oguri T. Case of the abscess type cutaneous nocardiosis. Med Mycol J. 2014; 55 (1), 19-23.

[66] Graham JM, Bartlett KB, Gonzalez A, Messina JL, Shenefelt PD. Primary cutaneous nocardiosis in an immunocompetent host following laser resurfacing. J Am Acad Dermatol. 2014; 71 (3), e93-4.

[67] Palmieri JR, Santo A, Johnson SE. Soil-acquired cutaneous nocardiosis on the forearm of a healthy male contracted in a swamp in rural eastern Virginia. Int Med Case Rep J. 2014; 7, 41-7.

[68] Shahapur PR, Peerapur B v, Shahapur RP, Honnutagi RM, Biradar MS. Lymphocutaneous nocardiosis caused by Nocardia otitidiscaviarum: A case report and review of literature. J Nat Sci Biol Med. 2014; 5 (1), 197-201.

[69] Lake EP, Hughart R, Jones ST, Kreppel A, Tsoukas M, Harrington AT. Cutaneous Nocardiosis: A Conspicuous Eyelid Eschar. J Pediatr. 2016; 177, 327.

[70] Numata S, Numata T, Gonoi T, Matsunaga K. Successful treatment of primary cutaneous Nocardia brasiliensis infection with oral potassium iodide. J Dermatol. 2016; 43 (7), 843-4.

[71] Oda R, Sekikawa Y, Hongo I. Primary Cutaneous Nocardiosis in an Immunocompetent Patient. Intern Med. 2017; 56 (4), 469-70.

[72] Lee TG, Jin WJ, Jeong WS, et al. Primary Cutaneous Nocardiosis Caused by Nocardia takedensis. Ann Dermatol. 2017; 29 (4), 471-5.

[73] Zhuang K, Tang J, Ran Y. Image Gallery: Acute primary cutaneous nocardiosis due to Nocardia brasiliensis. Br J Dermatol. 2017; 176 (5), e97.

[74] Tang A, Muggeo A, Rihn B, et al. Nocardiose cutanée chez une patiente immunocompétente A propos d’un cas et revue de la littérature. Ann Biol Clin (Paris). 2017; 75 (5), 576-9.

[75] Faccini-Martínez ÁA, Zanotti RL, Moraes MS, Falqueto A. Nodular Lymphangitis Syndrome. Am J Trop Med Hyg. 2017; 97 (5), 1282-4.

[76] Grau Pérez M, Casabella Pernas A, de la Rosa del Rey M del P, Torrado González R. Primary cutaneous nocardiosis: a pitfall in the diagnosis of skin infection. Infection. 2017; 45 (6), 927-8.

[77] Chen N, Qin Q, Sun K-D, Luo D, Cheng Q-H. An unusual successful treatment with non-sulfonamides: primary cutaneous nocardiosis caused by Nocardia brasiliensis. Ther Clin Risk Manag. 2018; 14, 1661-4.

[78] Ercibengoa M, Vicente D, Arranz L, Ugarte AS de, Marimon JM. Primary Cutaneous Nocardia brasiliensis in a Spanish Child. Clin Lab. 2018; 64 (10), 1769-72.

[79] Laube H. Primary Cutaneous Nocardiosis. Dtsch Arztebl Int. 2019; 116 (20), 362.

[80] Bandeira ID, Guimarães-Silva P, Cedro-Filho RL, de Almeida VRP, Bittencourt AL, Brites C. Primary cutaneous nocardiosis. J Dtsch Dermatol Ges. 2019; 17 (3), 327-9.

[81] Gudivada V, Gochhait D, Bhandary C, Mishra N, Siddaraju N. Cutaneous nocardiosis with discharging sinus clinically mimicking tuberculosis diagnosed by cytology. Diagn Cytopathol. 2019; 47 (9), 935-8.

[82] Tariq EF, Anwar MM, Khan UA. Primary Cutaneous Nocardiosis: A Rare Presentation of Nocardiosis. Cureus. 2019; 11 (10), e5860.

[83] Cases-Perera O, Aguilera-Saez J, Monte A, Rivas-Nicolls D, et al. Uncommon burn complication: skin nocardiosis. Ann Burns Fire Disasters. 2019; 32 (4), 289-93.

[84] Baek JO, Kim JS, Lee SK, Jeong JH, Lee MJ, Seo IH. Two cases of primary cutaneous nocardiosis caused by intralesional injection. Dermatol Ther. 2019; 32 (1), e12775.

[85] Al-Obaydi S, DeMaio J. Two Cases of Cutaneous Nocardiosis After a Natural Disaster. Cureus. 2019; 11 (12), e6278.

[86] Murata M, Fujita H, Gonoi T, Terui T. Case of localized cutaneous nocardiosis caused by Nocardia cyriacigeorgica. J Dermatol. 2019; 46 (12), e452-4.

[87] Steinmetz G, Panas K, Puffinbarger W. An Acute Nocardia Infection in a Pediatric Hand. J Hand Surg Am. 2019; 44 (4), 343.e1-343.e3.

[88] Bora A, Rathore L, Khatri PK, Chattopadhyay CS. A case report of Nocardia cyriacigeorgica presenting as cellulitis with multiple discharging sinuses. Indian J Pathol Microbiol. 2019; 62 (4), 621-3.

[89] Sayre JW, Lorch A, Gandhi M, Yancey R, Arora P. The First Report of Cutaneous Nocardia Concava Infection in the United States. Cureus. 2019; 11 (5), e4740.

[90] Mangieri NA, Guevara Nuñez D, Echavarría G, et al. Sporotrichoid nocardiosis by Nocardia brasiliensis. Rev Argent Microbiol. 2020; 53 (1), 43-7.

[91] Makadia S, Patel I, Soosaipillai I, Tarasiuk-Rusek A. First Case of Nocardia pseudobrasiliensis Causing Primary Cutaneous Nocardiosis in an Immunocompetent Patient. J Investig Med High Impact Case Rep. 2020; 8, 1-4.

[92] Zhou T, Wang X-Y, Deng D-Q, et al. Nocardia colli sp. nov., a new pathogen isolated from a patient with primary cutaneous nocardiosis. Int J Syst Evol Microbiol. 2020; 70 (5), 2981-7.

[93] Chen Y, Liu Y, Ding X-J, Chen Y-J, Wang L, Zhang Z-Z. Diagnosis and treatment of lymphocutaneous dermatosis caused by Nocardia brasiliensis: a case report. Ann Palliat Med. 2020; 9 (5), 3663-7.

[94] Acuner B, Cömert F. Recurrent Subcutaneous Abscess Due to Nocardia farcinica in an Immunocompetent Patient: A Case Report. Wound Manag Prev. 2021; 67 (5), 33-9.

[95] Bhandari M, Kathuria S, Khunger N, Sharma B. Mycetoma due to Nocardia Africana/Nova Treated Successfully with Cotrimoxazole and Moxifloxacin. Indian Dermatol Online J. 2021; 12 (2), 298-301.

[96] Margalit I, Lebeaux D, Tishler O, et al. How do I manage nocardiosis? Clin Microbiol Infect. 2021; 27 (4), 550-8.