Disseminated blastomycosis presenting as oligoarticular septic arthritis in a 12-year-old girl.код для вставкиСкачать
Arthritis & Rheumatism (Arthritis Care & Research) Vol. 53, No. 1, February 15, 2005, pp 138 –141 DOI 10.1002/art.20916 © 2005, American College of Rheumatology TRAINEE ROUNDS Disseminated Blastomycosis Presenting as Oligoarticular Septic Arthritis in a 12-Year-Old Girl ANDREW J. HEAD, LINDA K. MYERS, JEFFREY D. THOMPSON, STEVEN C. BUCKINGHAM, ROBERT B. SKINNER, JR Introduction Septic arthritis due to blastomycosis is rare, and when present is usually monarticular, although disease involving multiple joints has been described (1,2). Only 2 children have previously been reported to have arthritis as a presenting symptom of blastomycosis (3,4). Both of these cases were monarticular. We describe a case of an immunocompetent 12-year-old girl with disseminated blastomycosis who presented with skin lesions and arthritis involving 3 joints. To our knowledge, this is the ﬁrst pediatric patient reported with blastomycotic arthritis involving ⬎1 joint. Case report A previously healthy 12-year-old African American girl from Tennessee was referred to our institution with a 1-month history of knee pain and papulopustular skin lesions on the face that had not responded to treatment courses with oral cephalexin followed by oral clindamycin. The review of systems was signiﬁcant for low-grade fever for 3 days and a 10-pound weight loss over 2 months. Physical examination was remarkable for a temperature of 38.3°C and a limp favoring the left leg. Joint exam revealed a moderate effusion in the left knee that was warm and mildly tender. The right knee had a small effusion and mild tenderness. The left ankle was slightly swollen, warm, and tender as well. The rest of her joints were unremarkable. The skin examination revealed 3 5– 6 cm well-demarcated scaly verrucous plaques in varying stages on her forehead and chin. She also had 3 discrete nonAndrew J. Head, MD, Linda K. Myers, MD, Jeffrey D. Thompson, MD, Steven C. Buckingham, MD, Robert B. Skinner Jr, MD: University of Tennessee Health Science Center and Children’s Foundation Research Center at LeBonheur Children’s Medical Center, Memphis, Tennessee. Address correspondence to Andrew J. Head, MD, Division of Rheumatology, University of Tennessee Health Science Center, G326 Coleman Building, 956 Court Avenue, Memphis, TN 38163. Email: email@example.com. Submitted for publication April 23, 2004; accepted in revised form July 11, 2004. 138 AND tender 2–3 cm purple nodules: 1 on her left upper arm, 1 on the left palm, and 1 on the left foot (Figure 1). The peripheral blood leukocyte count was 15,000/mm3 (normal range 5,000 –13,000/mm3) with 78.4% neutrophils, the hemoglobin was 9.4 gm/dl (normal range 11–16 gm/dl), and the platelet count was 666,000/mm3 (normal range 140,000 – 450,000/mm3). Serum creatinine, aspartate aminotransferase, and alanine aminotransferase levels were normal. The erythrocyte sedimentation rate was 98 mm/hour (normal range 0 –13 mm/hour) and the C-reactive protein level was 21.0 mg/dl (normal range 0.3– 0.9 mg/dl). Blood cultures were negative. Arthrocentesis of the left knee yielded 10 cc of turbid ﬂuid. The synovial ﬂuid leukocyte count was 31,600/mm3 with 82% neutrophils and the synovial ﬂuid red blood cell count was 11,800/mm3. Bacterial culture of the synovial ﬂuid was negative. Serum assays for rheumatoid factor, antinuclear antibody, antistreptolysin-O antibody, human immunodeﬁciency virus antibody, and HLA–B27 yielded negative results. An evaluation of the patient’s immune function revealed normal numbers of B and T cells and normal responses to mitogens. Serum assays of total hemolytic complement and quantitative immunoglobulins revealed normal results. Radiographs of the knees demonstrated bilateral soft tissue swelling and a cyst-like lucency within the medial aspect of the right proximal tibial metaphysis. Magnetic resonance imaging (MRI) of the knees revealed a lesion involving the metaphysis extending into the epyphysis of the medial right proximal tibia and a similar lesion at the distal left femur. These lesions demonstrated a hyperintense signal with surrounding hypointense signal on T2 imaging, consistent with osteomyelitis or early Brodie’s abscess (Figure 2). A technetium-99 bone scan showed increased uptake in the right 7th and 8th ribs, right iliac crest, left distal femur, right medial tibial plateau, right distal tibia, and the occiput of the skull. A chest radiograph revealed perihilar inﬁltrates and computed tomography of the chest demonstrated left upper lobe consolidation with air bronchograms, a left-sided moderate pleural effusion, a right-sided rib lesion, a calciﬁed 3-mm Blastomycosis Presenting as Oligoarticular Arthritis 139 Figure 1. Skin lesions in various stages. Clockwise from top left: forehead, left arm, left palm, medial left foot. nodule at the right lung base, and multiple 3-mm hypodensities in the spleen consistent with abscesses. An MRI scan of her brain showed no lesions. A biopsy of one of the facial skin lesions was performed. Routine microscopy with hematoxylin and eosin showed epidermal hyperplasia with suppurative and granulomatous inﬂammation. Silver stain revealed thick-walled, broad-based budding yeast diagnostic of blastomycosis (Figure 3). Complement ﬁxing antibodies to Blastomyces dermatitidis were identiﬁed in her serum (titer 1:64 dilutions). The patient was hospitalized and intravenous ceftriaxone was administered initially. By hospital day number 1 the result of the skin biopsy was learned, at which time the ceftriaxone was stopped and intravenous amphotericin B administered (50 mg daily or 0.8 mg/kg/day). The patient defervesced within 48 hours of beginning amphotericin B. The joint pain resolved with resultant improvement in ambulation over a 1-week period. By hospital day number 8, she was discharged. The amphotericin B was continued daily for 14 days, at which point the treatment was changed to oral itraconazole 100 mg twice daily. One month following admission, the patient was afebrile, reported no joint pains, and was ambulating without difﬁculty. In addition, at 1-month followup, the skin lesions were resolving, but not completely healed. Discussion The clinical picture of pneumonia, septic arthritis, osteomyelitis, and verrucous skin lesions, with histopathologic Figure 2. Plain radiograph (left) and T2-weighted magnetic resonance image (right) of the right knee show a 4 ⫻ 6 cm spherical cyst with surrounding sclerosis within the medial aspect of the proximal tibial metaphysis extending into the epiphysis, consistent with Brodie’s abscess. 140 Figure 3. Silver-stained skin biopsy specimen under high power demonstrating thick-walled, broad-based budding yeast typical of Blastomyces dermatitidis (arrow). evidence of broad-based budding yeast and serologic evidence of B. dermatitidis infection together conﬁrm the diagnosis of disseminated blastomycosis in our patient. Blastomycosis is caused by the dimorphic fungus B. dermatitidis and is endemic in the midwestern, south central, and south eastern United States (5). The annual incidence of infection in the US is reported as 0.2/100,000 to 1.23/100,000, but reaches as high as 43.21/100,000 in endemic areas (6,7). An underlying immunosuppressive illness is reported in 12.5–25% of cases (7,8). Only 3–11% of cases occur in children (3,4). Frequently infection is asymptomatic, but disease involving multiple organ systems has been described (1– 4,6 –13). As in our patient, the initial symptoms of blastomycosis infection are frequently constitutional, including malaise, fever, chills, and weight loss. The portal of entry is the respiratory tract and the organism is inhaled as conidia, initially causing pneumonitis. This process can be asymptomatic (as in our patient) or present as acute or chronic pneumonia (5). Once within the alveolar macrophages, the infection is either controlled by the host immune system or spreads to distant organs hematogenously (10). Our patient demonstrated the typical skin and other organ involvement of disseminated blastomycosis. The skin is involved in 60 – 80% of cases and the lesions can be verrucous, ulcerative, or both. Dermal abscesses can form and spontaneously drain or cause sinus tracts. Osteomyelitis is common and the most common bones involved are (in descending order) vertebrae, pelvis, sacrum, skull, ribs, and long bones (5). Blastomycotic arthritis, although well described, is relatively uncommon (1– 4,6 –13). Joint pain is reported in 11% of patients and 8% have frank arthritis (11). The arthritis is usually monarticular, but a few cases involving multiple joints have been reported (1,2). Overall, the knee joint is most frequently affected (10). Diagnostic delays have been documented due to the ability of blastomycosis to mimic other more common conditions, such as bacterial arthritis (6). This was the case in our patient. Direct extension of osteomyelitis is a well-recognized cause of blastomycotic arthritis, but hematogenous seeding of the synovial membrane is thought to occur as well (11). The synovial ﬂuid of the blastomycotic joint is usually Head et al frankly purulent and, as in our patient, can mimic culturenegative bacterial arthritis (1). Reports in the literature suggest the synovial ﬂuid leukocyte count may vary from 450 to 100,000/mm3 with ⬎70% neutrophils (1,5). Synovial ﬂuid fungal cultures and KOH staining are useful in diagnosis and, when performed, have a diagnostic yield of 82% (11). The deﬁnitive diagnosis is made by culture or identiﬁcation of the organism from tissue samples or ﬂuid (5). To our knowledge there are 2 cases of blastomycotic arthritis reported in children and both of these were monarthritic at presentation (3,4). Neither reported synovial ﬂuid analysis. The ﬁrst patient was a 7-year-old girl who presented with a 1-month history of left ankle pain and swelling. This patient had a lytic lesion with a well-circumscribed border in the dome of the talus. She was treated with curettage of the bone lesion and oral ketoconazole 100 mg/day for 2 months. At 2 years followup there was no evidence of disease recurrence (3). The second case was an 8-year-old boy who presented with foot pain and constitutional symptoms. He developed skin lesions and painful swelling of the right ankle and left elbow within 2 months. He was treated with oral ketoconazole 150 mg/day for 2 months, but his condition worsened. Ketoconazole was withdrawn and intravenous amphotericin B initiated. He received a total of 1 mg/kg/day of amphotericin B for 1 month and then itraconazole 100 mg/day for 3 months. One year after treatment he had resolution of the skin lesions but residual arthralgias of the right ankle (4). Intravenous amphotericin is the ﬁrst-line antifungal agent for the management of life-threatening disseminated blastomycosis; however, therapy for some patients without central nervous system involvement may be switched to oral itraconazole after stabilization on intravenous amphotericin B (14). Our patient stabilized on a 2-week course of intravenous amphotericin B and was changed to oral itraconazole. We plan to continue itraconazole for 12 months to treat her osteomyelitis. She has reported no problems at followup and has demonstrated ongoing clinical improvement. In conclusion, septic arthritis due to blastomycosis is rare, and when present is usually monarticular, but can involve multiple joints and bones. The presence of pulmonary symptoms or typical skin lesions, if present, suggest the diagnosis. Blastomycotic arthritis should be included in the differential diagnosis of oligoarthritis in a patient living in an endemic area, particularly if associated with skin and bone lesions and constitutional symptoms. REFERENCES 1. Abril A, Campbell MD, Cotten VR Jr, Steckleberg JM, ElAzhary RA, O’Duffy JD. Polyarticular blastomycotic arthritis. J Rheumatol 1998;25:1019 –21. 2. Robert ME, Kauffman CA. Blastomycosis presenting as polyarticular septic arthritis. J Rheumatol 1988;15:1438 – 42. 3. MacDonald PB, Black GB, MacKenzie R. Orthopaedic manifestations of blastomycosis. J Bone Joint Surg Am 1990;72: 860 – 4. 4. Schutze GE, Hickerson SL, Fortin EM, Schellhase DE, Darville T, Gubbins PO, et al. Blastomycosis in children. 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