I I I IIIIIIIII I Disseminated Mycobacterium chelonae ssp. abscessus in an immunocompetent host and with a known portal of entry Bruce R. Nelson, MD, ~ Ronald P. Rapini, MD, b Richard J. Wallace, Jr., MD, e and Jaime A. Tschen, MD a Houston and Tyler, Texas A unique case is presented in which disseminated Mycobacterium chelonae ssp. ab- scessus was found in a normal immunocompetent host after a traumatic injury. Although disseminated disease is known to occur in immunocompromised and postsurgical pa- tients, this case is unusual in that it occurred in a patient with no evidence of immu- nodeficiency and with a known portal of entry. (J AM ACAD DERMATOL1989;20:909- 12.) Mycobacterium chelonae (formerly M. chelo- nei) is a ubiquitous organism found in soil and water. Together with M. fortuitum it is the major clinically significant species (Runyon group IV) of rapidly growing mycobacteria. M. chelonae has been recognized as a pathogen in a variety of hu- man diseases and has been identified as a cause of sporadic postsurgical infections, I3 postinjection abscesses, 4-7 posttraumatic inoculation, ~ pulmo- nary disease, 8qt and, in the immunosuppressed host, disseminated disease, l't2"t4 Cutaneous dis- semination in human beings, however, is rare. Most infections remain well localized and usually heal spontaneously, with incision and drainage or with antimicrobial therapy. The portal of entry or primary source of infec- tion is unknown in the reported cases of dissem- inated M. chelonae except for the obvious dissem- ination, for example, from contaminated pros- thetic heart valve endocarditis 1,tSt7 or indwelling intravenous catheters, m8.19 Furthermore, on the basis of the current literature, disseminated disease essentially has been limited to two groups of pa- tients: the immunocompromised and those under- From the Department of Dermatology, Baylor College of Medicine,' the Department of Dermatology, The University of Texas Health Science Center, Houston, b and the Department of Microbiology, The University of Texas Health Center, Tyler. ~ Reprint requests: Bn~ce R. Nelson, MD, One Baylor Plaza, Houston, TX 77030, going cardiovascular surgery. Two types of dis- seminated disease have been recognized. One is a noncutaneous form that occurs only rarely in pa- tients after surgery, especially in those with long- term intravenous access devices. These patients often have positive cultures from blood, bone mar- row, and liver specimens, The second type is a disseminated cutaneous disease with multiple skin lesions that occurs in immunosuppressed patients but that has no apparent relationship to long-term intravenous catheter use or to surgery. In this sec- ond group the portal of entry of the infection, to the best of our knowledge, has never been re- ported. In this article we present a case of disseminated M. chelonae ssp. abscessus that occurred in an immunocompetent host and with a known portal of entry. CASE REPORT A 35-year-old, otherwise healthy white woman was seen for evaluation of multiple erythematous and sub- cutaneous nodules, some of which were draining. The patient's past medical history was remarkable for an idiopathic seizure disorder controlled by phenytoin (Di- lantin) and for extensive third-degree bums suffered as a child. The patient had been in good health until April 1985, at which time, while she was working in her garden, a piece of wire fence penetrated the outer por- tion of her left thigh, The wound was slow to heal and within 3 to 4 weeks evolved into a tender, erythematous, subcutaneous nodule with a central draining sinus. Over 9O9
Transcript
I I I IIIIIIIII I
Disseminated Mycobacterium chelonae ssp. abscessus in an immunocompetent host and with a known portal of entry Bruce R. Nelson, MD, ~ Ronald P. Rapini, MD, b Richard J. Wallace, Jr., MD, e and Jaime A. Tschen, M D a Houston and Tyler, Texas
A unique case is presented in which disseminated Mycobacterium chelonae ssp. ab- scessus was found in a normal immunocompetent host after a traumatic injury. Although disseminated disease is known to occur in immunocompromised and postsurgical pa- tients, this case is unusual in that it occurred in a patient with no evidence of immu- nodeficiency and with a known portal of entry. (J AM ACAD DERMATOL 1989;20:909- 12.)
Mycobacterium chelonae (formerly M. chelo- nei) is a ubiquitous organism found in soil and water. Together with M. fortuitum it is the major clinically significant species (Runyon group IV) of rapidly growing mycobacteria. M. chelonae has been recognized as a pathogen in a variety of hu- man diseases and has been identified as a cause of sporadic postsurgical infections, I3 postinjection abscesses , 4-7 posttraumatic inoculation, ~ pulmo- nary disease, 8qt and, in the immunosuppressed host, disseminated disease, l't2"t4 Cutaneous dis- semination in human beings, however, is rare. Most infections remain well localized and usually heal spontaneously, with incision and drainage or with antimicrobial therapy.
The portal of entry or primary source of infec- tion is unknown in the reported cases of dissem- inated M. chelonae except for the obvious dissem- ination, for example, from contaminated pros- thetic heart valve endocarditis 1,tSt7 or indwelling intravenous catheters, m8.19 Furthermore, on the basis o f the current literature, disseminated disease essentially has been limited to two groups of pa- tients: the immunocompromised and those under-
From the Department of Dermatology, Baylor College of Medicine,' the Department of Dermatology, The University of Texas Health Science Center, Houston, b and the Department of Microbiology, The University of Texas Health Center, Tyler. ~
Reprint requests: Bn~ce R. Nelson, MD, One Baylor Plaza, Houston, TX 77030,
going cardiovascular surgery. Two types of dis- seminated disease have been recognized. One is a noncutaneous form that occurs only rarely in pa- tients after surgery, especially in those with long- term intravenous access devices. These patients often have positive cultures from blood, bone mar- row, and liver specimens, The second type is a disseminated cutaneous disease with multiple skin lesions that occurs in immunosuppressed patients but that has no apparent relationship to long-term intravenous catheter use or to surgery. In this sec- ond group the portal of entry of the infection, to the best of our knowledge, has never been re- ported.
In this article we present a case of disseminated M. chelonae ssp. abscessus that occurred in an immunocompetent host and with a known portal of entry.
CASE REPORT
A 35-year-old, otherwise healthy white woman was seen for evaluation of multiple erythematous and sub- cutaneous nodules, some of which were draining. The patient's past medical history was remarkable for an idiopathic seizure disorder controlled by phenytoin (Di- lantin) and for extensive third-degree bums suffered as a child. The patient had been in good health until April 1985, at which time, while she was working in her garden, a piece of wire fence penetrated the outer por- tion of her left thigh, The wound was slow to heal and within 3 to 4 weeks evolved into a tender, erythematous, subcutaneous nodule with a central draining sinus. Over
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Fig. 1. Healed site of the primary lesion located on the lateral aspect of the left thigh. Fig. 2. Group of subcutaneous nodules in varying stages of evolution located on the posterolateral surface of the proximal aspect of the right forearm in close proximity to scar. Fig. 3. Photomicrograph of biopsy specimen showing pseudoepitheliomatous hyperplasia and a diffuse dermal infiltrate. ( x 10.) Fig. 4. Higher-power view of granulomatous infiltrate. (Hematoxylin-eosin stain; x 50.)
the next 2 months, multiple new lesions developed, initially surrounding the primary lesion and later in- volving both the left and right thighs, forearms, and abdomen; all of the lesions failed to respond to multi- ple courses of oral antibiotics prescribed by the pa- tient's family physician. The primary lesion eventually evolved into a hyperpigmented scar (Fig. 1). Also of note was the consistent occurrence of new lesions at sites of trauma, such as minor abrasions and areas of venipuncture.
Physical examination revealed a moderately obese
white woman with disseminated subcutaneous nodules in various stages of evolution, sparing only the palms, soles, face, and areas of scarring from prior bums (Fig. 2). There was extensive scarring from her old burn injury with areas of retraction and evidence of skin grafting that involved the entire back, buttocks, and much of the right thigh and left breast. There was no evidence of lymphadenopathy, and the remainder of the physical examination was unremarkable.
A 4 mm punch biopsy specimen showed pseudoep- itheliomatous hyperplasia and a diffuse dem~al infil-
Volume 20 Number 5, Part 2 May 1989 Disseminated Mycobacterium chelonae ssp. abscessus 911
trate composed of lymphocytes, histiocytes, and mul- tinucleated giant cells (Figs. 3 and 4). Ziehl-Neelsen stain revealed rare acid-fast bacilli.
Cultures from four separate skin lesions on four sep- arate occasions consistently grew M. chelonae ssp. ab- scessus (this subspecies was identified at the Myeo- bacterial Reference Section of the Centers for Disease Control, Atlanta, Ga.); susceptibility testing by broth microdilution revealed the isolate to be resistant to all oral agents but susceptible to cefoxitin (minimal inhib- itory concentration = 16 g~g/ml) and amikacin (min- imal inhibitory concentration = 8 vg/ml). Blood cul- tures were negative. Complete blood cell count and SMA 20 results were within normal limits. Immuno- logic workup showed normal results (IgG, 1214 mg/dl; IgA, 176 mg/dl; IgM, 187 mg/dl; human im- munodeficiency virus antibody, negative; T4/T8 ratio, 0.95). The T tymphocytes comprised 74% of the total number of lymphocytes. Results of skin antigen testing were normal. The patient had a positive reaction to purified protein derivative, Candida, and tetanus and mumps vaccines. Chest x-ray examination was also normal.
The patient's lesions were completely cleared with a 10-week course of intravenous therapy, which in- cluded 4 weeks of amikacin and cefoxitin and 6 weeks of cefoxitin alone, which she took as an outpatient. The patient was unable to comply with the intravenous med- ication at home beyond this time, however, and the lesions recurred within 2 weeks and eventually were as extensive as they had been before the therapy. The patient's condition has been followed up for almost 2 years, with little change in her disease and without the appearance of any other medical disease.
DISCUSSION
M. chelonae ssp. abscessus was first described as a human pathogen in 1953 by Moore and Fre- r i c h s , 19 who isolated it from synovial cultures of a woman with chronic osteoarthritis of the left knee. This patient had sustained a left patellar dis- location and abrasion after a fall in a farmyard at age 14 years; 48 years later it became evident that she had been suffering from a localized infection with M. chelonae. After a patellectomy and syn- ovectomy the patient received intramuscular glu- teal streptomycin and penicillin injections and sub- sequently developed gluteal abscesses that, on cul- turing, yielded an identical organism. This was explained by postsurgical hematogenous spread, with a propensity of the organism to infect the areas of lowered resistance, a locus minoris resis-
tentiae, which allowed localization of the bacilli and subsequent growth in the areas of trauma. This concept, although rarely cited in the current lit- erature, proves to be especially interesting in light of our patient's clinical history.
Since its original description as a human patho- gen, M. chelonae has been identified as the caus- ative organism in numerous outbreaks of various injection abscesses, 4-7 pulmonary disease 8-t~ in pa- tients receiving hemodialysis and peritoneal dial- ysis, t6,2~ keratitis, 1 infection occurring after aug- mentation mammoplasty 3 or median sternotomy, J and, only rarely, disseminated disease. T M
The development of localized soft tissue infec- tion with nontuberculous mycobacteria has been recognized since the early 1900s and usually re- sults from traumatic inoculation. Despite chronic- ity and slow healing, without medical intervention these infections usually remain well localized and cutaneous dissemination is rare. When dissemi- nated disease does occur, it usually develops in an immunosuppressed host or from surgical contam- ination.
To the best of our knowledge there, has been only one other case of disseminated disease in an immunocompetent host. This patient was a 42-year-old man who was included by Wallace et al. ~7 in a review of rapidly growing mycobacteria and was subsequently lost to follow-up study. There was no known underlying disease, and re- sults of immunologic workup were negative on the basis of normal quantitative immunoglobulins, normal response to skin antigen testing, normal nitroblue tetrazolium test results (to rule out chronic granulomatous disease), normal complete blood cell count and differential, and normal re- sults of T and B cell analysis.
The rapidly growing atypical mycobacteria usu- ally are resistant in vitro and in vivo to most an- timycobacterial agents. Amikacin and cefoxitin have proved to be active against more than 90% of isolates, with the exception of M. chelonae ssp. chelonae, which is always resistant to cefoxitin.l Susceptibilities vary considerably between species and subspecies, and it is essential to have reliable susceptibility testing on which to base chemo- therapy treatment. Unfortunately this is available only at selected reference laboratories.
Disseminated disease, because of rapidly grow- ing atypical mycobacteria, has been previously re-
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ported, but, excluding surgical skin disease, the portal of entry or primary source of infection has never been identified. Our patient is unique, not only in that she had disseminated disease with a normal immune system but also because the portal of entry was identified.
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