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Successful management of neonatal cryoglobulinaemia after a gemellar pregnancy in a woman with symptomatic type I cryoglobulinaemia
  1. J Sibilia,
  2. O Feugeas,
  3. V Laugel,
  4. A Dreval,
  5. J Messer,
  6. J Goetz
  1. University of Strasbourg, France
  1. Correspondence to:
    Professor J Sibilia
    University Hospital of Strasbourg, avenue Molière Strasbourg, 67098 France; jean.sibiliawanadoo.fr

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CASE REPORT

Since 1996 a 32 year old woman had had cold-induced clinical manifestations: Raynaud’s phenomenon, livedo reticularis, necrotic and purpuric lesions on the legs, and acrocyanosis on the ears and fingers. She had no family history of cold intolerance, autoimmune disease, or recurrent thrombosis. In 1998 these symptoms were traced to a monoclonal IgG1λ cryoglobulin (type I) present at 1.5 g/l and precipitating at 27°C. Cold agglutinin and cryofibrinogen were absent while total complement (CH50) and C4 fraction were low. There were no antinuclear, anti-dsDNA, antineutrophil, anticardiolipin, or anti-β2-glycoprotein I antibodies, and viral serology was negative for hepatitis B and C and cytomegalovirus. A skin biopsy showed leucocytoclastic vasculitis and thrombosis of the capillaries related to the cryoglobulin. There were no renal, gastrointestinal, or neurological manifestations, but the patient had intermittent distal polyarthritis and was treated with pentoxifylline accompanied by protective measures against cold.

This mother had born a first healthy child in 1996 and had experienced no previous miscarriage. In 2000, during a second dichorionic gestation of twins, the lesions were progressive while the cryoglobulin persisted at 1.10 g/l. Because the IgG1λ chain can cross the placenta and the initial temperature of cryoprecipitation was 27°C, clinical manifestations could be expected in the newborns at room temperature. Treatment of the mother consisted only of protection against cold. Plasmaphereses were not performed as these do not totally eliminate cryoglobulin and have potential drawbacks, such as inducing premature labour by altering the plasma volume or hormone levels, or decreasing fetal nutrients and maternal and fetal serum immunoglobulin levels. General measures were defined to avoid cryoprecipitation at delivery: a room at 28°C, adapted clothes permitting medical supervision, warming of liquids to 37°C before perfusion to the mother, and placing the newborns in incubators.

The twins (female and male weighing 2440 g and 2690 g, respectively) were delivered after 39 weeks’ gestation and immediately put in incubators at 32°C. One and five minute Apgar scores were 10 for both neonates, and no cutaneous or visceral involvement was detected, despite the presence of cryoglobulin at 1.70 g/l in cord blood. Two days later the twins were placed in a room at 25°C, but after 3 hours small erythrocyanotic maculae appeared on the boy’s fifth finger (left hand) (fig 1) and second and fourth toes (left foot). These lesions were very similar to those seen in the mother, whereas careful examination of the girl disclosed no cutaneous manifestations. The twins were replaced in incubators and the lesions disappeared slowly within one week.

Figure 1

Cyanotic lesions of the boy’s fifth finger after exposure to room temperature

After another 2 days they were removed from the incubators and dressed warmly, no further lesions were observed and the dressing precautions could be gradually abandoned before discharge. The monoclonal IgG1λ cryoglobulin was detected in the serum of both neonates at comparable levels, but it was unfortunately not possible to obtain follow up of these results. Six months later the twins were healthy while the mother’s status remained stable with an unchanged serum cryoglobulin (1 g/l).

DISCUSSION

Maternal IgGs can cross the placenta, as is well illustrated by certain neonatal autoimmune diseases related to maternal autoantibodies.1 In the present case a monoclonal IgG1 cryoglobulin identified in the mother and her twin children was associated with transient cold-induced lesions in one child.2–4 This is the first report of a pathogenic neonatal effect due to the transplacental passage of a type I cryoglobulin. Although the lesions were probably favoured by the high precipitation temperature (27°C), many other physicochemical parameters can influence cryoprecipitation and hence might explain the difference between the two twins. Progressive clearance of the maternal IgG1 after its passive transfer may further explain the favourable outcome and absence of recurrence. Such cases are rare, probably on account of the low incidence of type I cryoglobulinaemia in women of child bearing age.5 Associations between pregnancy and other types of cryoglobulin have been described but without related neonatal lesions.6,7 In a patient with mixed type II cryoglobulin and hepatitis C infection, cryoglobulinaemia was responsible for placental lesions inducing pre-eclampsia, but no specific neonatal lesions were seen.8

The consequences for the fetus of the transplacental passage of IgG type I cryoglobulin are still unknown and the management of such pregnancies is difficult owing to the lack of a consensual procedure for the prevention of maternofetal complications. Corticosteroids or immunosuppressive drugs have failed to demonstrate any benefit. In our experience, protection against cold seems to be the only way to avoid precipitation of the cryoglobulin in the vessels of the mother and neonates with its pathogenic effects.

REFERENCES

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