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Noncervicofacial atypical mycobacterial lymphadenitis in childhood
Noncervicofacial Atypical Mycobacterial Lymphadenitis in Childhood By A.J.A. Holland, J. Holland, H.C.O. Martin, G. Cummins, C. Cooke-Yarborough, and D.T. Cass Sydney, Australia
Background/Purpose: Atypical mycobacterial (AM) lymphadenitis is common in children but rarely occurs outside the cervicofacial region. The authors report their experience in the diagnosis and management of noncervicofacial AM lymphadenitis.
22, and skin testing suggestive in 21 and equivocal in 2. Treatment was by excision in 28 and drainage with or without curettage in 9. At a median follow-up of 19.7 months, disease had recurred in 4 patients, none of whom had been treated initially by excision.
Methods: A retrospective review was conducted of cases diagnosed at our institution between January 1976 and December 1999, based on positive culture of atypical mycobacteria or consistent histology with supportive skin testing.
Conclusions: Atypical mycobacterial infection is an uncommon cause of noncervicofacial lymphadenitis in children. It typically presents with a 4-week history of painless regional lymphadenopathy that may follow penetrating trauma. If untreated, the overlying skin becomes involved with a violaceous discoloration, and ulceration may occur. Definitive treatment involves complete surgical excision, preferably before suppuration extending beyond the involved lymph nodes. J Pediatr Surg 36:1337-1340. Copyright © 2001 by W.B. Saunders Company.
Results: Thirty-seven patients were identified over the 23year review period. The median age was 4.3 years (range, 8 months to 13 years and 5 months), with 19 boys and 17 girls. The median duration of symptoms was 4 weeks, and the most commonly affected sites were the inguinal region (n ⫽ 17), axilla (n ⫽ 8), and lower limb (n ⫽ 6). Preceding local trauma was described in 10 patients and a viral illness in 4. Laboratory culture for atypical mycobacteria was positive in
C
LINICALLY SIGNIFICANT infections secondary to nontuberculous or atypical mycobacteria (AM) are a well-documented cause of cervical lymphadenitis in childhood, particularly in preschool age girls.1-6 Since the identification of AM in 1950s and the recognition of their prevalence within the environment, their importance as the most frequent cause of mycobacterial lymphadenitis in children has been increasingly acknowledged.7-10 The incidence has been estimated as 1.21 per 100,000 compared with 0.3 per 100,000 for Mycobacteria tuberculosis, although clearly defined diagnostic criteria often have not been used.2 The majority of cases have involved cervicofacial lymph nodes. This is thought to reflect on the role of the oropharynx as the portal of entry, with breaks in the lining of the toddler’s mouth from erupting dentition in combination with exploratory mouthing of objects allowing entry of mycobacteria.4 Alternatively, the tonsils may act as reservoirs for infection.2 Although noncervicofacial AM lymphadenitis has been reported previously either as an isolated case or as a few cases within larger series, there has been no detailed review or series described in the literature.1-3,5,6,11,12 We report our experience in the diagnosis and management of this condition. MATERIALS AND METHODS Children with noncervicofacial AM lymphadenitis were identified from a retrospective search of the medical records database over 23
INDEX WORDS: Atypical mycobacteria, noncervicofacial lymphadenopathy, incidence, treatment.
years at The Royal Alexandra Hospital for Children and Westmead Hospital between January 1976 and December 1999. Patients were included on the basis of lymphadenitis outside the cervicofacial region that was proven to be caused by AM either on the basis of positive culture for AM or histologic features consistent with mycobacterial infection in conjunction with supportive skin testing. Histologic characteristics of AM infection were defined as caseating granulomatous inflammation within the involved lymph node, or Ziehl-Neelsen or auramine staining for acid and alcohol-fast bacilli. Skin testing indicating AM infection was defined as greater than 9 mm reaction at 72 hours to a 10 IU intradermal injection of avian Mantoux or a greater response to avian versus human Mantoux.13 The patient records were reviewed and data collected on age, sex, presenting features and location of lymphadenopathy, results of inves-
From the Departments of Academic Surgery, Douglas Cohen Department of Paediatric Surgery, and Department of Histopathology, The Children’s Hospital at Westmead, Royal Alexandra Hospital for Children, The University of Sydney, and the Department of Clinical Microbiology, Mayne Health–Laverty Pathology, Sydney, New South Wales, Australia. Presented at the 73rd Annual Scientific Congress of the Royal Australasian College of Surgeons, Melbourne, May 7-12, 2000. Address reprint requests to Mr Andrew J.A. Holland, Department of Academic Surgery, Division of Surgery, The Children’s Hospital at Westmead, Royal Alexandra Hospital for Children, The University of Sydney, Locked Bag 4001, Westmead NSW 2145, Australia. Copyright © 2001 by W.B. Saunders Company 0022-3468/01/3609-0004$35.00/0 doi:10.1053/jpsu.2001.26363
Journal of Pediatric Surgery, Vol 36, No 9 (September), 2001: pp 1337-1340
1337
1338
HOLLAND ET AL
tigation and treatment, length of subsequent clinical review, and complications including recurrent disease.
RESULTS
Case Example A 1-year, 10-month-old girl presented with a 3-month history of an erythematous swelling in the right groin. The discoloration progressed to a purple hue over an 8-week period before discharging thick, purulent material. An indolent ulcer then formed, which continued to discharge for the next 4 weeks. There was no history of preceding trauma. Examination found a 1.5-cm-diameter ulcer with slough in its base just inferior to the inguinal ligament in the right groin (Fig 1). There was a 2-cm lymph node inferomedial to the ulcer (Fig 2). The remainder of the physical examination was normal, and a provisional diagnosis of AM lymphadenitis was made. Skin testing with human Mantoux was negative but strongly positive by avian Mantoux, consistent with the clinical diagnosis. The ulcer and adjacent involved lymph node were excised. Histopathology of the node showed caseating granulomatous inflammation (Fig 3). Culture grew mycobacteria identified as part of the avium, intracellulare, and scrofulaceum complex, although the species was not differentiated further. This organism was resistant to conventional antituberculous chemotherapeutic agents, including rifampicin, isoniazid, streptomycin, and pyrazinamide. The wound healed satisfactorily, and there was no evidence of recurrent disease during 12 months of follow-up. Series Thirty-seven patients were identified over the 23-year review period. Over the same period there was an average of 25 cases per year of cervicofacial AM lymphad-
Fig 1.
Ulceration right groin with slough in base.
Fig 2. Lymphadenopathy secondary to AM infection inferomedial to ulcer right groin.
enitis presenting to our institution, giving a relative incidence of 6.4% for noncervicofacial cases. There was no evidence of seasonal variation. The median age was 4.3 years, with a range from 8 months to 13 years, 5 months. The sex ratio was approximately equal, with 19 boys and 17 girls. The duration of symptoms ranged from 2 to 16 weeks with a median of 4 weeks. The regions of infection are indicated in Table 1, the most common sites being inguinal (n ⫽ 17), axilla (n ⫽ 8) and lower limb (n ⫽ 6). Antecedent regional trauma had occurred in 10 (27%) patients between 2 weeks and 9 months (median 6 weeks) before the onset of lymphadenitis. This involved a lower limb abrasion or laceration in 8 patients, a median sternotomy in 1 patient, and a compound forearm fracture in another. In 4 patients there appeared to have been a preceding viral illness, consisting of a fever, nausea, and malaise, which settled several days before the development of noncervicofacial lymphadenitis. Differential antigen skin testing was positive for AM infection in 21 of those tested, equivocal in 2 cases, and
Fig 3. Histopathology of excised node shows caseating granulomatous inflammation (H&E original magnification ⴛ 5.7).
NONCERVICOFACIAL LYMPHADENITIS
1339
Table 1. Site of Atypical Mycobacterial Lymphadenitis Site
No. (n ⫽ 37)
Percent*
Inguinal Axilla Lower limb Upper limb Thorax Abdomen
17 8 6 4 1 1
46 22 16 11 3 3
*Rounding prevents total of 100%.
not performed in 14 cases. Laboratory culture for AM was positive in 22 (60%), and the species identified are shown in Table 2. In one case Serratia marcescens was isolated later after AM lymphadenitis had been diagnosed on the basis of positive skin testing and histologic features. This patient subsequently had chronic osteomyelitis secondary to Serratia marcescens. Treatment was by excision in 28 or incision and drainage with or without curettage in 9 patients. Antibacterial prophylaxis, in the form of a single perioperative intravenous dose of an antistaphylococcal antibiotic, was used in 17. In those patients treated by excision, absorbable sutures were used in all but 3 cases. Median documented follow-up was 19.7 months with a range from 6 weeks to 5 years. Disease recurred in 4 patients, all but 1 of whom had been treated initially with incision and drainage only (Table 3). There were no surgical complications. No patients had systemic disease or disease at a second site requiring treatment with antimycobacterial agents. DISCUSSION
Cervical AM lymphadenitis has been recognized at least since 500 AD10; the term scrofula is derived from the Latin for a pregnant sow and presumably reflects the similarity in appearance between porcine neck folds and the distortion of normal tissues that occurs from untreated mycobacterial lymphadenitis. Mycobacteria scrofulaceum was first identified as a cause of cervical AM lymphadenitis in children in 1956.7 Runyon14 subsequently classified the atypical or “anonymous” mycobacteria as a cause of respiratory disease in 1959. AM remain the usual mycobacterial cause of cervical lymphadenitis in childhood, in contrast to adults in whom Mycobacteria tuberculosis and Mycobacteria bovis Table 2. Culture Results Atypical mycobacteria
No. (n ⫽ 22)
Percent*
MAIS complex† M avium-intracellulare M fortuitum M marinum M scrofulaceum M terrae
15 2 2 1 1 1
68 9 9 5 5 5
*Rounding prevents total of 100%. † Mycobacterium avium-intracellulare-scrofulaceum complex.
Table 3. Results of Treatment Treatment
No. (n ⫽ 37)
Recurrence (%)
Incision and drainage Incision and drainage plus curettage Excision
7 2 28
3 (43) 1 (50) 0 (0)
predominate.8 More recent evidence suggests that AM infections are becoming more common in adults, perhaps because of a rise in the prevalence of human immunodeficiency virus, which may lead to a follow-on effect in children.15 Since the first reported case of noncervicofacial AM lymphadenitis in 1976, there have been sporadic cases reported in the literature with a remarkably consistent incidence of 4.5% to 7.5% relative to cervicofacial AM disease.1-3,5,6,11,12 The relative infrequency of this condition makes early clinical diagnosis difficult; often, the true significance of the history and examination findings may only be appreciated once the results of histopathology and microbiologic culture have been obtained. Pediatric surgeons need to consider this diagnosis in light of a history of previous trauma, often several weeks or even months earlier, followed by the development of regional lymphadenitis in a child in whom there is no record of contact with a cat. In such patients, differential skin testing is highly likely to identify those cases secondary to AM and should prompt surgical excision with the purulent material and tissue obtained cultured for AM.13 If untreated, as with AM lymphadenitis in the head and neck, a violaceous discolouration develops in the overlying skin that may subsequently ulcerate. The prevalence of AM within the environment suggests that the likely entry site would be a breach of skin or a mucosal barrier, but this was only documented in just over a quarter of our cases. In the majority of patients there was no obvious mechanism of infection. In part, this may represent the limitations of a retrospective review. Of interest, however, is the rarity of noncervicofacial AM lymphadenitis given the frequency with which children sustain minor soft tissue injuries of the limbs and torso. The disparity between cervicofacial and noncervicofacial AM lymphadenitis represents a combination of factors: if the diagnosis is not considered, skin testing and appropriate microbiologic cultures may not be requested. Lack of such confirmatory evidence resulted in the exclusion of a number of cases in our series. There may be a role in equivocal cases for fine-needle aspiration biopsy to confirm the diagnosis before definitive surgery.16 Probably of more significance in terms of risk of development of the disease, however, is the interaction between environmental and patient factors. The patho-
1340
HOLLAND ET AL
genicity of the mycobacterium and the mode of inoculation must influence the likelihood of a clinically significant infection. Typically, in our patients, the trauma consisted of a penetrating injury with a contaminated object such as a nail or piece of glass, and this also has been reported in the adult literature.17 Finally, the patients themselves may have a predisposition to AM infection, such as an inherited deficiency of antigen processing.18 As illustrated in 4 of our patients, the process also may be influenced by a prodromal viral illness that subtly alters the balance between AM and host defenses to allow mycobacterial infection to occur. Because many children not suffering AM lymphadenitis similarly will provide a history of a recent viral illness, the potential importance of this interaction and the subsequent development of infection is difficult to determine. That the immune system does have an important role in preventing AM infection is illustrated by the protective effect of BCG vaccination at an early age against subsequent AM lymphadenitis.19 As shown in our study, and in others of cervicofacial AM lymphadenitis, the most effective treatment remains complete local excision.4,9 Incision and drainage alone is much less likely to be curative and commonly leads to recurrence.2,9,10 Because there were no complications secondary to absorbable sutures in our series, we would advocate their
use in healthy tissue after complete excision. Prevention of secondary bacterial infection by a single perioperative dose of an antistaphylococcal agent would seem logical, although there were no secondary infections in those patients for whom this approach was not used in our series. Antimycobacterial agents such as clarithromycin, azithromycin, ethambutol, and rifabutin have been shown to be effective in disseminated AM infection.20-22 The development of resistance has been documented on monotherapy, and use of at least 2 agents is now recommended.22 Poor compliance may be an issue in children given the unpleasant taste of the medication and duration of therapy from 2 to 8 weeks. In addition, their role in localized disease remains poorly defined, and given the excellent results of definitive surgery their use should perhaps be restricted to those cases in which there is a significant risk of trauma to adjacent structures. Noncervicofacial AM lymphadenitis in childhood is uncommon, but early clinical diagnosis and elective surgical excision is associated with low morbidity and a satisfactory long-term outcome. Pediatric surgeons should contemplate the diagnosis in those children who present with painless regional lymphadenopathy, often of several weeks duration, particularly if after a penetrating injury or associated with overlying violaceous discolouration of the skin.
REFERENCES 1. Taha AM, Davidson PT, Bailey WC: Surgical treatment of atypical mycobacterial lymphadenitis in children. Pediatr Infec Dis 4:664-667, 1985 2. Sigalet D, Lees G, Fanning A: Atypical tuberculosis in the pediatric patient: Implications for the pediatric surgeon. J Pediatr Surg 27:1381-1384, 1992 3. Wolinsky E: Mycobacterial lymphadenitis in children: A prospective study of 105 nontuberculous cases with long-term follow-up. Clin Infect Dis 20:954-963, 1995 4. Wright JE: Non-tuberculous mycobacterial lymphadenitis. Aust N Z J Surg 66:225-228, 1996 5. Evans MJ, Smith NM, Thornton CM, et al: Atypical mycobacterial lymphadenitis in childhood—A clinicopathological study of 17 cases. J Clin Pathol 51:925-927, 1998 6. Hazra R, Robson CD, Perez-Atayde AR, et al: Lymphadenitis due to nontuberculous mycobacteria in children: Presentation and response to therapy. Clin Infect Dis 28:123-129, 1999 7. Prissick FH, Masson AM: Cervical lymphadenitis in children caused by chromogenic mycobacteria. Canad Med Assoc J 75:798-803, 1956 8. Lai KK, Stottmeier KD, Sherman IH, et al: Mycobacterial cervical lymphadenopathy. Relation of etiologic agents to age. J Am Med Assoc 251:1286-1288, 1984 9. Bodenstein L, Altman RP: Cervical lymphadenitis in infants and children. Sem Pediatr Surg 3:134-141, 1994 10. Fergusson JAE, Simpson E: Surgical treatment of atypical mycobacterial cervicofacial adenitis in children. Aust N Z J Surg 69:426-429, 1999 11. Anseline PS, Wright JE: Mycobacterial lymphadenitis. Med J Aust 1:244-245, 1976 12. Koruda MJ, Bell LM, Ross AJ III: Atypical mycobacterial mesenteric lymphadenitis in childhood presenting as an abdominal mass. J Pediatr Surg 23:526-528, 1988
13. Daley AJ, Isaacs D: Differential avian and human tuberculin skin testing in non-tuberculous mycobacterial infection. Arch Dis Child 80:377-379, 1999 14. Runyon EH: Anonymous mycobacteria in pulmonary disease. Med Clin North Am 43:290, 1959 15. Yates MD, Grange JM: Bacteriological survey of tuberculous lymphadenitis in southeast England, 1981-1989. J Epidemiol Commun Health 46:332-335, 1992 16. Orford JE, Gollow I, Brennan B, et al: Fine needle aspiration biopsy in children. Aust N Z J Surg 67:785-788, 1997 17. Holland J, Smith C, Childs PA, et al: Surgical management of cutaneous infection caused by atypical mycobacterial after penetrating injury: the hidden dangers of horticulture. J Trauma Inj Infec Crit Care 42:337-340, 1997 18. D’Souza S, Levin M, Faith A, et al: Defective antigen processing associated with familial disseminated mycobacteriosis. Clin Exp Immunol 103:35-39, 1996 19. Kroger L, Katila ML, Korppi M, et al: Skin test reactivity to atypical mycobacteria among healthy Finnish preschool children vaccinated with BCG vaccine at birth. Acta Paediatr 81:891-895, 1992 20. Piedimonte G, Wolford ET, Fordham LA, et al: Mediastinal lymphadenopathy caused by Mycobacterium avium-intracellulare complex in a child with normal immunity: Successful treatment with anti-mycobacterial drugs and laser bronchoscopy. Pediatr Pulmonol 24:287-291, 1997 21. Metchock BG, Nolte FS, Wallace RJ Jr: Mycobacterium, in Murray PR, Baron EJ, Pfaller MA, et al (eds): Manual of Clinical Microbiology. Washington, DC, ASM Press, 1999, pp 399-437 22. Powderly WG: Treatment of infection due to mycobacterium avium complex. Pediatr Infect Dis J 18:468-469, 1999
Background/Purpose: Atypical mycobacterial (AM) lymphadenitis is common in children but rarely occurs outside the cervicofacial region. The authors report their experience in the diagnosis and management of noncervicofacial AM lymphadenitis.
22, and skin testing suggestive in 21 and equivocal in 2. Treatment was by excision in 28 and drainage with or without curettage in 9. At a median follow-up of 19.7 months, disease had recurred in 4 patients, none of whom had been treated initially by excision.
Methods: A retrospective review was conducted of cases diagnosed at our institution between January 1976 and December 1999, based on positive culture of atypical mycobacteria or consistent histology with supportive skin testing.
Conclusions: Atypical mycobacterial infection is an uncommon cause of noncervicofacial lymphadenitis in children. It typically presents with a 4-week history of painless regional lymphadenopathy that may follow penetrating trauma. If untreated, the overlying skin becomes involved with a violaceous discoloration, and ulceration may occur. Definitive treatment involves complete surgical excision, preferably before suppuration extending beyond the involved lymph nodes. J Pediatr Surg 36:1337-1340. Copyright © 2001 by W.B. Saunders Company.
Results: Thirty-seven patients were identified over the 23year review period. The median age was 4.3 years (range, 8 months to 13 years and 5 months), with 19 boys and 17 girls. The median duration of symptoms was 4 weeks, and the most commonly affected sites were the inguinal region (n ⫽ 17), axilla (n ⫽ 8), and lower limb (n ⫽ 6). Preceding local trauma was described in 10 patients and a viral illness in 4. Laboratory culture for atypical mycobacteria was positive in
C
LINICALLY SIGNIFICANT infections secondary to nontuberculous or atypical mycobacteria (AM) are a well-documented cause of cervical lymphadenitis in childhood, particularly in preschool age girls.1-6 Since the identification of AM in 1950s and the recognition of their prevalence within the environment, their importance as the most frequent cause of mycobacterial lymphadenitis in children has been increasingly acknowledged.7-10 The incidence has been estimated as 1.21 per 100,000 compared with 0.3 per 100,000 for Mycobacteria tuberculosis, although clearly defined diagnostic criteria often have not been used.2 The majority of cases have involved cervicofacial lymph nodes. This is thought to reflect on the role of the oropharynx as the portal of entry, with breaks in the lining of the toddler’s mouth from erupting dentition in combination with exploratory mouthing of objects allowing entry of mycobacteria.4 Alternatively, the tonsils may act as reservoirs for infection.2 Although noncervicofacial AM lymphadenitis has been reported previously either as an isolated case or as a few cases within larger series, there has been no detailed review or series described in the literature.1-3,5,6,11,12 We report our experience in the diagnosis and management of this condition. MATERIALS AND METHODS Children with noncervicofacial AM lymphadenitis were identified from a retrospective search of the medical records database over 23
INDEX WORDS: Atypical mycobacteria, noncervicofacial lymphadenopathy, incidence, treatment.
years at The Royal Alexandra Hospital for Children and Westmead Hospital between January 1976 and December 1999. Patients were included on the basis of lymphadenitis outside the cervicofacial region that was proven to be caused by AM either on the basis of positive culture for AM or histologic features consistent with mycobacterial infection in conjunction with supportive skin testing. Histologic characteristics of AM infection were defined as caseating granulomatous inflammation within the involved lymph node, or Ziehl-Neelsen or auramine staining for acid and alcohol-fast bacilli. Skin testing indicating AM infection was defined as greater than 9 mm reaction at 72 hours to a 10 IU intradermal injection of avian Mantoux or a greater response to avian versus human Mantoux.13 The patient records were reviewed and data collected on age, sex, presenting features and location of lymphadenopathy, results of inves-
From the Departments of Academic Surgery, Douglas Cohen Department of Paediatric Surgery, and Department of Histopathology, The Children’s Hospital at Westmead, Royal Alexandra Hospital for Children, The University of Sydney, and the Department of Clinical Microbiology, Mayne Health–Laverty Pathology, Sydney, New South Wales, Australia. Presented at the 73rd Annual Scientific Congress of the Royal Australasian College of Surgeons, Melbourne, May 7-12, 2000. Address reprint requests to Mr Andrew J.A. Holland, Department of Academic Surgery, Division of Surgery, The Children’s Hospital at Westmead, Royal Alexandra Hospital for Children, The University of Sydney, Locked Bag 4001, Westmead NSW 2145, Australia. Copyright © 2001 by W.B. Saunders Company 0022-3468/01/3609-0004$35.00/0 doi:10.1053/jpsu.2001.26363
Journal of Pediatric Surgery, Vol 36, No 9 (September), 2001: pp 1337-1340
1337
1338
HOLLAND ET AL
tigation and treatment, length of subsequent clinical review, and complications including recurrent disease.
RESULTS
Case Example A 1-year, 10-month-old girl presented with a 3-month history of an erythematous swelling in the right groin. The discoloration progressed to a purple hue over an 8-week period before discharging thick, purulent material. An indolent ulcer then formed, which continued to discharge for the next 4 weeks. There was no history of preceding trauma. Examination found a 1.5-cm-diameter ulcer with slough in its base just inferior to the inguinal ligament in the right groin (Fig 1). There was a 2-cm lymph node inferomedial to the ulcer (Fig 2). The remainder of the physical examination was normal, and a provisional diagnosis of AM lymphadenitis was made. Skin testing with human Mantoux was negative but strongly positive by avian Mantoux, consistent with the clinical diagnosis. The ulcer and adjacent involved lymph node were excised. Histopathology of the node showed caseating granulomatous inflammation (Fig 3). Culture grew mycobacteria identified as part of the avium, intracellulare, and scrofulaceum complex, although the species was not differentiated further. This organism was resistant to conventional antituberculous chemotherapeutic agents, including rifampicin, isoniazid, streptomycin, and pyrazinamide. The wound healed satisfactorily, and there was no evidence of recurrent disease during 12 months of follow-up. Series Thirty-seven patients were identified over the 23-year review period. Over the same period there was an average of 25 cases per year of cervicofacial AM lymphad-
Fig 1.
Ulceration right groin with slough in base.
Fig 2. Lymphadenopathy secondary to AM infection inferomedial to ulcer right groin.
enitis presenting to our institution, giving a relative incidence of 6.4% for noncervicofacial cases. There was no evidence of seasonal variation. The median age was 4.3 years, with a range from 8 months to 13 years, 5 months. The sex ratio was approximately equal, with 19 boys and 17 girls. The duration of symptoms ranged from 2 to 16 weeks with a median of 4 weeks. The regions of infection are indicated in Table 1, the most common sites being inguinal (n ⫽ 17), axilla (n ⫽ 8) and lower limb (n ⫽ 6). Antecedent regional trauma had occurred in 10 (27%) patients between 2 weeks and 9 months (median 6 weeks) before the onset of lymphadenitis. This involved a lower limb abrasion or laceration in 8 patients, a median sternotomy in 1 patient, and a compound forearm fracture in another. In 4 patients there appeared to have been a preceding viral illness, consisting of a fever, nausea, and malaise, which settled several days before the development of noncervicofacial lymphadenitis. Differential antigen skin testing was positive for AM infection in 21 of those tested, equivocal in 2 cases, and
Fig 3. Histopathology of excised node shows caseating granulomatous inflammation (H&E original magnification ⴛ 5.7).
NONCERVICOFACIAL LYMPHADENITIS
1339
Table 1. Site of Atypical Mycobacterial Lymphadenitis Site
No. (n ⫽ 37)
Percent*
Inguinal Axilla Lower limb Upper limb Thorax Abdomen
17 8 6 4 1 1
46 22 16 11 3 3
*Rounding prevents total of 100%.
not performed in 14 cases. Laboratory culture for AM was positive in 22 (60%), and the species identified are shown in Table 2. In one case Serratia marcescens was isolated later after AM lymphadenitis had been diagnosed on the basis of positive skin testing and histologic features. This patient subsequently had chronic osteomyelitis secondary to Serratia marcescens. Treatment was by excision in 28 or incision and drainage with or without curettage in 9 patients. Antibacterial prophylaxis, in the form of a single perioperative intravenous dose of an antistaphylococcal antibiotic, was used in 17. In those patients treated by excision, absorbable sutures were used in all but 3 cases. Median documented follow-up was 19.7 months with a range from 6 weeks to 5 years. Disease recurred in 4 patients, all but 1 of whom had been treated initially with incision and drainage only (Table 3). There were no surgical complications. No patients had systemic disease or disease at a second site requiring treatment with antimycobacterial agents. DISCUSSION
Cervical AM lymphadenitis has been recognized at least since 500 AD10; the term scrofula is derived from the Latin for a pregnant sow and presumably reflects the similarity in appearance between porcine neck folds and the distortion of normal tissues that occurs from untreated mycobacterial lymphadenitis. Mycobacteria scrofulaceum was first identified as a cause of cervical AM lymphadenitis in children in 1956.7 Runyon14 subsequently classified the atypical or “anonymous” mycobacteria as a cause of respiratory disease in 1959. AM remain the usual mycobacterial cause of cervical lymphadenitis in childhood, in contrast to adults in whom Mycobacteria tuberculosis and Mycobacteria bovis Table 2. Culture Results Atypical mycobacteria
No. (n ⫽ 22)
Percent*
MAIS complex† M avium-intracellulare M fortuitum M marinum M scrofulaceum M terrae
15 2 2 1 1 1
68 9 9 5 5 5
*Rounding prevents total of 100%. † Mycobacterium avium-intracellulare-scrofulaceum complex.
Table 3. Results of Treatment Treatment
No. (n ⫽ 37)
Recurrence (%)
Incision and drainage Incision and drainage plus curettage Excision
7 2 28
3 (43) 1 (50) 0 (0)
predominate.8 More recent evidence suggests that AM infections are becoming more common in adults, perhaps because of a rise in the prevalence of human immunodeficiency virus, which may lead to a follow-on effect in children.15 Since the first reported case of noncervicofacial AM lymphadenitis in 1976, there have been sporadic cases reported in the literature with a remarkably consistent incidence of 4.5% to 7.5% relative to cervicofacial AM disease.1-3,5,6,11,12 The relative infrequency of this condition makes early clinical diagnosis difficult; often, the true significance of the history and examination findings may only be appreciated once the results of histopathology and microbiologic culture have been obtained. Pediatric surgeons need to consider this diagnosis in light of a history of previous trauma, often several weeks or even months earlier, followed by the development of regional lymphadenitis in a child in whom there is no record of contact with a cat. In such patients, differential skin testing is highly likely to identify those cases secondary to AM and should prompt surgical excision with the purulent material and tissue obtained cultured for AM.13 If untreated, as with AM lymphadenitis in the head and neck, a violaceous discolouration develops in the overlying skin that may subsequently ulcerate. The prevalence of AM within the environment suggests that the likely entry site would be a breach of skin or a mucosal barrier, but this was only documented in just over a quarter of our cases. In the majority of patients there was no obvious mechanism of infection. In part, this may represent the limitations of a retrospective review. Of interest, however, is the rarity of noncervicofacial AM lymphadenitis given the frequency with which children sustain minor soft tissue injuries of the limbs and torso. The disparity between cervicofacial and noncervicofacial AM lymphadenitis represents a combination of factors: if the diagnosis is not considered, skin testing and appropriate microbiologic cultures may not be requested. Lack of such confirmatory evidence resulted in the exclusion of a number of cases in our series. There may be a role in equivocal cases for fine-needle aspiration biopsy to confirm the diagnosis before definitive surgery.16 Probably of more significance in terms of risk of development of the disease, however, is the interaction between environmental and patient factors. The patho-
1340
HOLLAND ET AL
genicity of the mycobacterium and the mode of inoculation must influence the likelihood of a clinically significant infection. Typically, in our patients, the trauma consisted of a penetrating injury with a contaminated object such as a nail or piece of glass, and this also has been reported in the adult literature.17 Finally, the patients themselves may have a predisposition to AM infection, such as an inherited deficiency of antigen processing.18 As illustrated in 4 of our patients, the process also may be influenced by a prodromal viral illness that subtly alters the balance between AM and host defenses to allow mycobacterial infection to occur. Because many children not suffering AM lymphadenitis similarly will provide a history of a recent viral illness, the potential importance of this interaction and the subsequent development of infection is difficult to determine. That the immune system does have an important role in preventing AM infection is illustrated by the protective effect of BCG vaccination at an early age against subsequent AM lymphadenitis.19 As shown in our study, and in others of cervicofacial AM lymphadenitis, the most effective treatment remains complete local excision.4,9 Incision and drainage alone is much less likely to be curative and commonly leads to recurrence.2,9,10 Because there were no complications secondary to absorbable sutures in our series, we would advocate their
use in healthy tissue after complete excision. Prevention of secondary bacterial infection by a single perioperative dose of an antistaphylococcal agent would seem logical, although there were no secondary infections in those patients for whom this approach was not used in our series. Antimycobacterial agents such as clarithromycin, azithromycin, ethambutol, and rifabutin have been shown to be effective in disseminated AM infection.20-22 The development of resistance has been documented on monotherapy, and use of at least 2 agents is now recommended.22 Poor compliance may be an issue in children given the unpleasant taste of the medication and duration of therapy from 2 to 8 weeks. In addition, their role in localized disease remains poorly defined, and given the excellent results of definitive surgery their use should perhaps be restricted to those cases in which there is a significant risk of trauma to adjacent structures. Noncervicofacial AM lymphadenitis in childhood is uncommon, but early clinical diagnosis and elective surgical excision is associated with low morbidity and a satisfactory long-term outcome. Pediatric surgeons should contemplate the diagnosis in those children who present with painless regional lymphadenopathy, often of several weeks duration, particularly if after a penetrating injury or associated with overlying violaceous discolouration of the skin.
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