596
Brief clinical and laboratory observations
8. Smith BS: Idiopathic pulmonary haemosiderosis and rheumatoid arthritis, Br Med J 1:1403, 1966. 9. Haslock I, and Wright V: The gut and arthritis, Rheumatol Rehabil 13:51, 1974.
The Journal of Pediatrics April 1979
10. Stapleton FB, Kennedy J, Nousia-Arvanitakis N, and Linshaw MA: Hyperuricosuria due to high-dose pancreatic extract therapy in cystic fibrosis, N Engl J Med 295:246, 1976.
Salmonella reactive arthritis: Clues to diagnosis Judith Levine, M.D.,* Paul J. Honig, M.D., and Timothy Boyle, M,D., Philadelphia, Pa.
A REACTIVE ARTHRITIS may occur following intestinal infection with Yersinia, I Shigella, ~ and Salmonella. ~ The clinical events that precede the arthritis are subtle and frequently overlooked. We report a case of arthritis following Salmonella gastroenteritis to highlight the features of this entity. CASE REPORT A 14-year-old white boy was admitted for evaluation of fever and polyarticular arthritis. He had been well until two weeks prior to admission when he developed anorexia, abdominal cramping, diarrhea, and fatigue. The diarrhea occurred three to four times a day and was described as watery, but without blood or mucus. He had no fever, rash, coryza, vomiting, or joint pain. The patient's 17-year-old sibling had experienced similar symptoms one week earlier, which cleared without treatment. The patient's symptoms resolved over a period of five days and he resumed normal activity. One week prior to admission the patient developed painful swelling of the feet and ankles; walking became difficult and anorexia and malaise were present. Over the next five days painful swelling developed in both knees, the left wrist, and the proximal interphalangeal and distal interphalangeal joints of the right index finger. The patient also developed late afternoon fevers to 38.5~ He lost 10 pounds during the two weeks. At admission he denied rash, headache, eye discharge, sore throat, stiff neck, cough, abdominal pain, back pain, dysuria, urinary frequency, or urethral discharge. His bowel movements were now normal, with one formed stool per day. Past medical history and family history were noncontributory. No family members had arthritis or inflammatory bowel disease, Physical examination revealed a well-developed, wellnourished white boy with a temperature of 37~ weight 40.2 kg, blood pressure 100/68 mm Hg, respiration 16 per minute. No rash or adenopathy was present. Results of his chest, heart, abdominal, and neurotogic examinations were normal. The rectal examination was normal except for guiac positive stool. There was tenderness and swelling without heat or erythema in the followingjoints: the interphalangeal joints of all toes, both ankles and knees, the left wrist, and the proximal interphalangeal and From The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine. *Reprint address: The Children's Hospital of Philadelphia, 34th & Civic Center Blvd., Philadelphia, PA 19104.
distal interphalangeal joints of the fight index finger. Both the dorsum and soles of the feet were swollen and tender. Laboratory data included a hemoglobin concentration of 12 gm/dl and hematocrit of 36%. The WBC was 12,400 with a normal differential, and the r sedimentation rate was 103 mm. Urinalysis, electrolytes, BUN, Ca, P, alkaline phosphatase, SGOT, SGPT, total protein, albumin globulin ratio, uric acid, immunoglobulins, ANA, LE prep, rheumatoid factor, DNA binding and PPD were all normal. Throat, blood, and urine cultures were negative. A chest roentgenogram, sacroiliac joint views, and colon and upper gastrointestinal contrast studies were also normal. Roentgenograms of the knees, ankles, wrists, and hands were unremarkable other than demonstrating soft tissue swelling. Stool cultures grew Salmonella typhimurium on three occasions, and febrile agglutinins were positive for paratyphoid B in a titer of 1:640. Proctoscopy revealed erythematous, edematous rectal mucosa with increased friability. A rectal biopsy demonstrated submucosal edema and a mononudear inflammatory infiltrate compatible with mild inflammatory reaction. The boy's hospital course was characterized by migratory joint swelling and tenderness, dally fevers to 39~ anorexia, and malaise. He was treated with aspirin 80 mg/kg/day, with rapid improvement in joint symptoms and gradual defervescence of the fever over one week. Over a five-month period the patient was gradually weaned from aspirin and remains completely asympt0matic. Serologic typing was positive for the HLA B27 histocompatibility antigen in this patient. (This antigen is found on the surface of most body cells other than erythrocytes. Susceptibility of an individual to a particular disease seems closely linked to the presence of specific histocompatibility antigens?) DISCUSSION Postinfectious Salmonella arthritis occurs infrequently in children. Nevertheless, it should be considered as part of the differential diagnosis in a child presenting with swollen joints. Recognition o f certain critical aspects of the clinical constellation will direct the physician to this entity and the proper studies leading to the diagnosis. The particular joint involved should greatly influence the direction o f the work-up. This child had large joint and distal interphalangeal joint involvement. The latter is generally found in Reiter syndrome, psoriatic arthritis, and the reactive arthritis syndromes. Another helpful clue 0022-3476/79/400596+02500.20/0 9 1979 The C. V. Mosby Co.
Volume 94 Number 4
Brief clinical and laboratory observations
in the diagnosis, as demonstrated by our patient, was the history of prodromal diarrhea. The stool cultures growing Salmonella and the elevated febrile agglutinin titers provided additional laboratory confirmation of the suspected diagnosis. Finally, the finding of histocompatibility antigen HLA B27 provided further supporting evidence for the diagnosis of Salmonella reactive arthritis. A review s.... shows that patients with Salmonella reactive arthritis usually develop joint symptoms one and one-half to two weeks after an initial diarrheal episode. The arthritis tends to be polyarticular, with knees and ankles affected most frequently. Swelling and tenderness are features more prominent than joint erythema. The arthritis is frequently migratory, with rapid recurrence and regression of symptoms. Exacerbations are frequently accompanied by systemic manifestations that include fever and malaise. Sedimentation rates tend to be high, whereas white blood cell counts are minimally elevated. When joint effusions are tapped, they are invariably sterile. Radiographs of involved joints reveal only soft tissue swelling. Recent studies have shown a highly significant association between the presence of histoc0mpatibility antigen HLA B27 and the post Salmonella reactive arthritis syndrome." ' In patients who were tissue typed following an outbreak of Salmonella enteritis in Sweden, a distinct correlation was noted; 69.2% of infected individuals with arthrfis were positive forlthe histocompatibility antigen as opposed to 7.7% of infected controls who were without joint involvement. The gene frequency in their healthy controls was reported to be 10%. The HLA B27 locus is also found in greater frequency in individuals with reactive arthritis following Yersinia 8 and Shigella 2 infections, as well as Reiter syndrome? One example of the Reiter triad occurring in conjunction with Salmonella arthritis has been described. 1~Reiter syndrome is difficult to diagnose in children and s o m e overlap with the syndrome described in this report may exist. 11
597
Reactive Salmonella arthritis should be entertained as a cause of joint inflammation in children with the history of prodromal diarrhea, rapid onset of a migratory arthritis, and objective findings of multiple joint involvement, including the distal interphalangeal joints. The diagnosis may then be confirmed by establishing the presence of Salmonella infection via positive stool cultures and elevated agglutinin titers. Further supporting evidence includes the presence of the histocompatibility antigen HLA B27 in the individual. REFERENCES
1. Ahvonen P, Sievcrs K, and Aho K: Arthritis associated with Yersinia enterocofitica infection, Acta Rheum Scand 15:232, 1969. 2. Aho K, Ahvoneu P, Alkio P, Lassus A, Sairanen E, Seivers K, and Tiilikainen A: HLA 27 in reactive arthritis following infection, Ann Rheum Dis 34:(Suppl 1): 29, 1975. 3. Schaller J, and Omenn G: The histocompatibility system and human disease, J Pm)XATR88:913, 1976. 4. Hakansson U, Low B, Eitrem R, and Winblad S: HLA 27 and reactive arthritis in an outbreak of salmonellosis, Tissue Antigens 6:366, 1975. 5. Vartiainen J, and Hurri L: Arthritis due to salmonella typhimurium, Acta Med Stand 175:771, 1964. 6. Aho K, Ahyonen P, Lassus A, Sievers K, and Tiilikainen A: HLA antigen 27 and reactive arthritis, Lancet 2:157, 1973. 7. Hakansson U, Eitrem R, Low B, and Winblad S: HLA antigen B27 in eases with joint affections in an Outbreak of salmonellosis, Scand J Infect Dis 8:245, 1976. 8. Aho K, Ahvonen P, Lassus A, Sievers K, and Tiilikainen A: HLA 27 in reactive arthritis! a study ofyersiniS arthritis and Reiter's disease, Arthritis Rheum I7:421, 1974. 9. Arnett F, MeClusky E, Schacter B, and London R: Incomplete Reiter's syndrome discrim!nating features and HLA W27 in diagnosis, Aiin Intern Med 84:8, 1976. 10. lveson JME, Nanda BS, Hancock JAH, Pownall PJ, Wright V: Reiter's disease in three boys, Ann Rheum Dis 34:364, 1975. I 1. Singsen B, Bernstein B, Koster-King K. Glovsky M, and Hanson V: Reiter's syndrome in Childhood, Arthritis Rheum 20(Suppl):402; 1977.
Localized osseous cryptococcosis Jay R. Poliner, M.D.,* E. Brooks Wilkins, M.D., and Gerald W. Fernald, M.D., Chapel Hill, N.C.
From the Departments of Family Medicine and Pediatrics, University of North Carolina School of Medicine, and the North Carolina Memorial Hospital. *Reprint address: Departmentof Family Medicine, Case Western Reserve UniversitySchool of Medicine, 2119 Abington Rd., Cleveland, OH 44106.
0022-3476/79/400597+03500.30/0 9 1979 The C. V. Mosby Co.
I N r E c T I O N with Cryptococcus neoformans most commonly involves the central nervous system and lungs; bone is involved in 5 to 10% of patient s. Isolated bone lesions are uncommon and should prompt a search for infection in other organs. This report describes an other-
Brief clinical and laboratory observations
8. Smith BS: Idiopathic pulmonary haemosiderosis and rheumatoid arthritis, Br Med J 1:1403, 1966. 9. Haslock I, and Wright V: The gut and arthritis, Rheumatol Rehabil 13:51, 1974.
The Journal of Pediatrics April 1979
10. Stapleton FB, Kennedy J, Nousia-Arvanitakis N, and Linshaw MA: Hyperuricosuria due to high-dose pancreatic extract therapy in cystic fibrosis, N Engl J Med 295:246, 1976.
Salmonella reactive arthritis: Clues to diagnosis Judith Levine, M.D.,* Paul J. Honig, M.D., and Timothy Boyle, M,D., Philadelphia, Pa.
A REACTIVE ARTHRITIS may occur following intestinal infection with Yersinia, I Shigella, ~ and Salmonella. ~ The clinical events that precede the arthritis are subtle and frequently overlooked. We report a case of arthritis following Salmonella gastroenteritis to highlight the features of this entity. CASE REPORT A 14-year-old white boy was admitted for evaluation of fever and polyarticular arthritis. He had been well until two weeks prior to admission when he developed anorexia, abdominal cramping, diarrhea, and fatigue. The diarrhea occurred three to four times a day and was described as watery, but without blood or mucus. He had no fever, rash, coryza, vomiting, or joint pain. The patient's 17-year-old sibling had experienced similar symptoms one week earlier, which cleared without treatment. The patient's symptoms resolved over a period of five days and he resumed normal activity. One week prior to admission the patient developed painful swelling of the feet and ankles; walking became difficult and anorexia and malaise were present. Over the next five days painful swelling developed in both knees, the left wrist, and the proximal interphalangeal and distal interphalangeal joints of the right index finger. The patient also developed late afternoon fevers to 38.5~ He lost 10 pounds during the two weeks. At admission he denied rash, headache, eye discharge, sore throat, stiff neck, cough, abdominal pain, back pain, dysuria, urinary frequency, or urethral discharge. His bowel movements were now normal, with one formed stool per day. Past medical history and family history were noncontributory. No family members had arthritis or inflammatory bowel disease, Physical examination revealed a well-developed, wellnourished white boy with a temperature of 37~ weight 40.2 kg, blood pressure 100/68 mm Hg, respiration 16 per minute. No rash or adenopathy was present. Results of his chest, heart, abdominal, and neurotogic examinations were normal. The rectal examination was normal except for guiac positive stool. There was tenderness and swelling without heat or erythema in the followingjoints: the interphalangeal joints of all toes, both ankles and knees, the left wrist, and the proximal interphalangeal and From The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine. *Reprint address: The Children's Hospital of Philadelphia, 34th & Civic Center Blvd., Philadelphia, PA 19104.
distal interphalangeal joints of the fight index finger. Both the dorsum and soles of the feet were swollen and tender. Laboratory data included a hemoglobin concentration of 12 gm/dl and hematocrit of 36%. The WBC was 12,400 with a normal differential, and the r sedimentation rate was 103 mm. Urinalysis, electrolytes, BUN, Ca, P, alkaline phosphatase, SGOT, SGPT, total protein, albumin globulin ratio, uric acid, immunoglobulins, ANA, LE prep, rheumatoid factor, DNA binding and PPD were all normal. Throat, blood, and urine cultures were negative. A chest roentgenogram, sacroiliac joint views, and colon and upper gastrointestinal contrast studies were also normal. Roentgenograms of the knees, ankles, wrists, and hands were unremarkable other than demonstrating soft tissue swelling. Stool cultures grew Salmonella typhimurium on three occasions, and febrile agglutinins were positive for paratyphoid B in a titer of 1:640. Proctoscopy revealed erythematous, edematous rectal mucosa with increased friability. A rectal biopsy demonstrated submucosal edema and a mononudear inflammatory infiltrate compatible with mild inflammatory reaction. The boy's hospital course was characterized by migratory joint swelling and tenderness, dally fevers to 39~ anorexia, and malaise. He was treated with aspirin 80 mg/kg/day, with rapid improvement in joint symptoms and gradual defervescence of the fever over one week. Over a five-month period the patient was gradually weaned from aspirin and remains completely asympt0matic. Serologic typing was positive for the HLA B27 histocompatibility antigen in this patient. (This antigen is found on the surface of most body cells other than erythrocytes. Susceptibility of an individual to a particular disease seems closely linked to the presence of specific histocompatibility antigens?) DISCUSSION Postinfectious Salmonella arthritis occurs infrequently in children. Nevertheless, it should be considered as part of the differential diagnosis in a child presenting with swollen joints. Recognition o f certain critical aspects of the clinical constellation will direct the physician to this entity and the proper studies leading to the diagnosis. The particular joint involved should greatly influence the direction o f the work-up. This child had large joint and distal interphalangeal joint involvement. The latter is generally found in Reiter syndrome, psoriatic arthritis, and the reactive arthritis syndromes. Another helpful clue 0022-3476/79/400596+02500.20/0 9 1979 The C. V. Mosby Co.
Volume 94 Number 4
Brief clinical and laboratory observations
in the diagnosis, as demonstrated by our patient, was the history of prodromal diarrhea. The stool cultures growing Salmonella and the elevated febrile agglutinin titers provided additional laboratory confirmation of the suspected diagnosis. Finally, the finding of histocompatibility antigen HLA B27 provided further supporting evidence for the diagnosis of Salmonella reactive arthritis. A review s.... shows that patients with Salmonella reactive arthritis usually develop joint symptoms one and one-half to two weeks after an initial diarrheal episode. The arthritis tends to be polyarticular, with knees and ankles affected most frequently. Swelling and tenderness are features more prominent than joint erythema. The arthritis is frequently migratory, with rapid recurrence and regression of symptoms. Exacerbations are frequently accompanied by systemic manifestations that include fever and malaise. Sedimentation rates tend to be high, whereas white blood cell counts are minimally elevated. When joint effusions are tapped, they are invariably sterile. Radiographs of involved joints reveal only soft tissue swelling. Recent studies have shown a highly significant association between the presence of histoc0mpatibility antigen HLA B27 and the post Salmonella reactive arthritis syndrome." ' In patients who were tissue typed following an outbreak of Salmonella enteritis in Sweden, a distinct correlation was noted; 69.2% of infected individuals with arthrfis were positive forlthe histocompatibility antigen as opposed to 7.7% of infected controls who were without joint involvement. The gene frequency in their healthy controls was reported to be 10%. The HLA B27 locus is also found in greater frequency in individuals with reactive arthritis following Yersinia 8 and Shigella 2 infections, as well as Reiter syndrome? One example of the Reiter triad occurring in conjunction with Salmonella arthritis has been described. 1~Reiter syndrome is difficult to diagnose in children and s o m e overlap with the syndrome described in this report may exist. 11
597
Reactive Salmonella arthritis should be entertained as a cause of joint inflammation in children with the history of prodromal diarrhea, rapid onset of a migratory arthritis, and objective findings of multiple joint involvement, including the distal interphalangeal joints. The diagnosis may then be confirmed by establishing the presence of Salmonella infection via positive stool cultures and elevated agglutinin titers. Further supporting evidence includes the presence of the histocompatibility antigen HLA B27 in the individual. REFERENCES
1. Ahvonen P, Sievcrs K, and Aho K: Arthritis associated with Yersinia enterocofitica infection, Acta Rheum Scand 15:232, 1969. 2. Aho K, Ahvoneu P, Alkio P, Lassus A, Sairanen E, Seivers K, and Tiilikainen A: HLA 27 in reactive arthritis following infection, Ann Rheum Dis 34:(Suppl 1): 29, 1975. 3. Schaller J, and Omenn G: The histocompatibility system and human disease, J Pm)XATR88:913, 1976. 4. Hakansson U, Low B, Eitrem R, and Winblad S: HLA 27 and reactive arthritis in an outbreak of salmonellosis, Tissue Antigens 6:366, 1975. 5. Vartiainen J, and Hurri L: Arthritis due to salmonella typhimurium, Acta Med Stand 175:771, 1964. 6. Aho K, Ahyonen P, Lassus A, Sievers K, and Tiilikainen A: HLA antigen 27 and reactive arthritis, Lancet 2:157, 1973. 7. Hakansson U, Eitrem R, Low B, and Winblad S: HLA antigen B27 in eases with joint affections in an Outbreak of salmonellosis, Scand J Infect Dis 8:245, 1976. 8. Aho K, Ahvonen P, Lassus A, Sievers K, and Tiilikainen A: HLA 27 in reactive arthritis! a study ofyersiniS arthritis and Reiter's disease, Arthritis Rheum I7:421, 1974. 9. Arnett F, MeClusky E, Schacter B, and London R: Incomplete Reiter's syndrome discrim!nating features and HLA W27 in diagnosis, Aiin Intern Med 84:8, 1976. 10. lveson JME, Nanda BS, Hancock JAH, Pownall PJ, Wright V: Reiter's disease in three boys, Ann Rheum Dis 34:364, 1975. I 1. Singsen B, Bernstein B, Koster-King K. Glovsky M, and Hanson V: Reiter's syndrome in Childhood, Arthritis Rheum 20(Suppl):402; 1977.
Localized osseous cryptococcosis Jay R. Poliner, M.D.,* E. Brooks Wilkins, M.D., and Gerald W. Fernald, M.D., Chapel Hill, N.C.
From the Departments of Family Medicine and Pediatrics, University of North Carolina School of Medicine, and the North Carolina Memorial Hospital. *Reprint address: Departmentof Family Medicine, Case Western Reserve UniversitySchool of Medicine, 2119 Abington Rd., Cleveland, OH 44106.
0022-3476/79/400597+03500.30/0 9 1979 The C. V. Mosby Co.
I N r E c T I O N with Cryptococcus neoformans most commonly involves the central nervous system and lungs; bone is involved in 5 to 10% of patient s. Isolated bone lesions are uncommon and should prompt a search for infection in other organs. This report describes an other-
