Familial Chondrocalcinosis and HLA System

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Eight patients who scored 4 points for PSS in the NZCS did not meet the ARA criteria. Three of these 8 patients required a biopsy to score 4 points, 2 had CREST syndrome, and the remaining 3 had sclerodactyly with Raynaud’s phenomenon or renal or esophageal involvement. Esophageal involvement was more sensitive and specific than lung fibrosis in the NZCS, because the latter feature occurred in PN cases, a category not included in the American study. Calcinosis and telangiectasis were not selected as ARA minor criteria, and in the American study 5 complete or incomplete CREST patients were excluded. The New Zealand study was a smaller retrospective study, and clinical categorization depended on one physician’s concept of the connective tissue diseases. Nevertheless, this independent scoring system also identified the cutaneous manifestations of PSS as being sensitive and specific. However, only 50.8% of patients had the major criterion compared with 91% of patients selected for the American study (1). New Zealand patients probably had less severe PSS, because the New Zealand study was populationbased with less selection bias. The American study selected a “combination of fewest items” for the ARA criteria that were to aid the “proper evaluation of the results of clinical investigations and therapeutic trials.” The more lengthy New Zealand scoring system was designed for an epidemiologic study. For such studies, adjustments to the minor criteria may be necessary if the highly specific ARA criteria were expected to include patients with mild disease and without the major criterion. As envisaged by the ARA committee, modifications are required if CREST is considered part of the spectrum of PSS, as in the New Zealand study.

P. L. J. TAN R. D. WIGLEY Research Laboratory, Public Hospital Palmerston North, New Zealand G . B. BORMAN National Health Statistics Centre Wellington, New Zealand 1. Masi AT, Rodnan GP, Medsger TA, et al: Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum 23:581-590, 1980 2. Borman GB: Medical geography and its contribution to the aetiology of rare systemic connective tissue diseases (thesis). Massey University, New Zealand, 1975

3. Wigley R, Borman B: Medical geopraphy and the aetiolo-

gy of rare connective tissue diseases in New Zealand. SOC Sci Med 14D: 175-183, 1980

Familial chondrocalcinosis and HLA system To the Editor: The association between articular chondrocalcinosis and the genes of the HLA complex has been repeatedly studied, but the results have been either negative or unclear. When the studies were carried out with unrelated patients, no association was found. In some families with two or more affected members, a possible parallel between segregation of HLA genotype and susceptibility to the disease has been reported. From this, we may suspect a linkage between HLA genes and susceptibility genes for chondrocalcinosis. If we assign the designations A and B to the paternal haplotypes (the antigens coded by the HLA loci of one chromosome), and C and D to the maternal haplotypes, the four possible genotypes in the offspring are: N C , N D , B/C, and B/D. Two siblings affected can share 2 haplotypes (e.g., NC-NC), 1 haplotype (e.g., MC-BIC), or 0 haplotypes (e.g., NCB/D) . When siblings are HLA identical (2 haplotypes in common), a recessive model of inheritance linked to the genes of the HLA complex might be postulated. On the other hand, haploidentity ( I haplotype in common) between affected siblings may indicate a dominant model of inheritance linked to the HLA genes. A great number of family studies would be necessary to give a significant value to the findings. Thus, the positive data have a “statistical limitation.” A single negative finding, however, is enough evidence to discard a simple model of inheritance linked to the genes of the HLA complex. In unrelated chondrocalcinosis patients, no clear-cut association to any HLA antigen has been found, but an association was found in some affected family members with one or two HLA haplotypes in common (1,2). We report here the HLA genotyping of a family in which 2 cases of chondrocalcinosis exist in 2 siblings; 1 sibling (sibling 2) has a polyarticular form of chondrocalcinosis, and the other has an ankylosing form. Results are shown in Table 1. Affected siblings are HLA different (0 haplotypes in common).

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Table 1. Results of HLA genotyping in a family with 2 cases of chondrocalcinosis* ....

A

Father Aw32 CW- Bw5O

C

B

A1

Bw56

D

Cwl

Mother A2 CW- Bw52 A28 CW- Bw49

A

Aw32 CW- Bw50

A

Aw32

CW- BwSO

B

AI

C

A2

D

A28

Cw- Bw4Y

C

A2 CW- € 3 ~ 5 2

CW- Bw52

Sibling I Sibling 2 (PACh) Sibling 3

Cwl

Sibling 5

Sibling 4

Bw56

B

D

AI

Cwl

Bw56

‘ A 2 8 CW- Bw49 Sibling 6 (ACh)

_________~

* A , B, C, and D

=

HLA haplotypes; PACh

polyarticular chondrocalcinosis; ACh

From this negative finding, we can hypothesize that susceptibility genes of chondrocalcinosis (if they exist) are not linked to the HLA genes. Finally, we want to stress that these studies, although informative, should be continued and supported by more cases.

A. NUREZ-ROLDAN Laboratorio de Immunologia Ciudad Sanitaria “Virgen del Rocio” Sevilla, Spain J . SANCHEZ-BURSON J. PRIETO E. PUJOL Hospital Universitario Sevilla Spain

1. Nyulassy S, Stefanovic J , Sitaj S , Zitnan D: HLA

system in articular chondrocalcinosis. Arthritis Rheum 19:39 1-393, 1976 2. Reginato AJ, Schiapachasse V , Zmijewski C M , Schumacher HR, Fuentes C, Galdamez M: HLA antigens in chondrocalcinosis and ankylosing chondrocalcinosis. Arthritis Rheum 22:928-932, 1979

Charcot-Leyden crystals in synovial fluid To the Editor: Charcot-Leyden crystals have been found in a variety of conditions associated with eosinophilia, including asthma, allergy, granulocytic leukemia, and parasitic diseases ( 1,2). Since eosinophilia is exceedingly uncommon in synovial fluid, and since only a few cases have been reported with eosinophilic counts

=

ankylosing chondrocalcinosis.

higher than 20% (3,4), the fact that these crystals have never been described either in synovium or in synovial fluid is not entirely surprising. We report the formation of Charcot-Leyden crystals in the synovial fluid of a 46-year-old white woman. Swelling of her right knee developed 12 days after a sclerosing injection of a varix in her right leg. A generalized pruriginous rash appeared suddenly 30 minutes after an intraarticular injection of steroids. An arthrocentesis was performed 6 days after the onset of the arthritis, resulting in removal of 100 ml of a turbid yellow fluid, specific gravity 1.037, refraction index 1.343, viscosity of medium quality, a poor Ropes test, and negative rheumatoid factor (Hyland RA test). The synovial cell count was WBC 5,700/mm3, including 43% eosinophils, 9% basophils, 5% neutrophils, 17% monocytes, and 26% lymphocytes. The blood cell count was WBC 8,200/mm3, including 76% of neutrophils, 9% lymphocytes, 8% monocytes, and 7% eosinophils. Intracellular Charcot-Leyden crystals were observed in wet preparations of the synovial fluid under the polarizing microscope. The crystals demonstrated a weakly positive birefringence. In a previous observation, they were erroneously described with an optically negative sign (5). The typical hexagonal bipyramid shape of the crystals was particularly well identified with Nomarski interference contrast (Figure 1). Charcot-Leyden crystals are formed in vivo or in vitro by aggregation of a protein from degenerating eosinophils (2). The crystal protein was recently identified as eosinophil lysophospholipase (6). In fresh wet preparations these crystals may appear within a few seconds in the presence of a detergent (5) or within a few minutes after a slight pressure on the coverslip (7). Thus, these crystals may represent merely in vitro