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We report two cases of primary Raynaud’s phenomenon in 16 year old monozygotic female twins.
The twins were admitted to the dermatology department with a one year history of the sudden onset of episodic purple lesions on both hands. Presentation of the lesions in the twins was synchronous. After careful questioning, we determined that it was usually induced by emotion or cold temperature. On dermatological examination, the order of purple discolouration, erythema, and pallor was observed symmetrically in both hands. There was no history of smoking, the use of drugs, occupational hazard, or trauma. They also had sensations of coolness and paraesthesia. Photographs of the hands were obtained during an attack and used to confirm the history. We also performed a provocative test—namely, immersion of the patient’s hand in ice water for three minutes, to confirm the diagnosis. Nailfold capillaroscopy examination also demonstrated normal capillaries. The female twins were born at 38 weeks of gestation by caesarean section. Obstetric anamnesis was normal. The twins’ past medical history was unremarkable. Their parents were relatives, but the family history was negative for cutaneous or collagen vascular disease.
Results of laboratory examinations, including complete blood count, biochemistry, urine analysis, thyroid function tests, serum cryoglobulins, complement levels, immunoglobulins, erythrocyte sedimentation rate, and C reactive protein, were normal. Serological testing for antinuclear antibody, anticardiolipin antibodies, and antibody to Ro, La, dsDNA, ribonucleoprotein, and Smith antigen were negative. The twins were diagnosed as monozygotic with almost complete certainty by examining the ABO blood type, HLA typing, fingerprints, and from the physical resemblance between them. Identical HLA antigens were HLA-A2, A24, B17, B57, Cw3, Cw6, DR4, and DR11. Medical evaluation subsequently disclosed no disorder known to cause secondary Raynaud’s phenomenon (RP).
RP is an exaggerated vascular response to cold temperature or emotional stress, primarily seen in young women. It is classified into primary or idiopathic without underlying disease and secondary when it is related to various medical problems.1,2 Clinical criteria are used to distinguish between patients with uncomplicated or primary RP, and those with secondary RP. The suggested criteria for primary RP are symmetric attacks; the absence of tissue necrosis, ulceration or gangrene; the absence of a secondary cause on the basis of a patient’s history and general physical examination; normal nailfold capillaries; a negative test for antinuclear antibody; and a normal erythrocyte sedimentation rate.2,3 The most common diseases associated with secondary RP are scleroderma, mixed connective tissue disease, systemic lupus erythematosus, occlusive vascular disease, drug effects, haematological abnormalities, and use of vibrating tools.1,3 Primary RP occasionally evolves into a connective tissue disease, most commonly scleroderma.2,4
Even though the cause of primary RP is not known, increased α2 sympathetic receptor activity on vessels, endothelial dysfunction, deficiency of calcitonin gene related peptide, protein-containing nerves, or some central thermoregulatory defect have been implicated.4,5 A genetic cause for primary RP was first suggested by Lewis and Pickering, based on an apparent familial aggregation of primary RP.2,7,8 MacGregor et al first assessed the genetic basis of RP in a population based twin study and found a substantial genetic contribution to the symptoms of RP.9 Recently, three potential candidate genes have been described in the genetic susceptibility to primary RP.10
To the best of our knowledge, this is the first report documenting the occurrence of primary RP in monozygotic twins. Association with HLA antigens, parental consanguinity, and development in identical twins may indicate that genetic factors have a role in the occurrence of this disease. Larger series of twins and investigation of multicase families are needed to clarify the genetic component in the pathogenesis of primary RP.
We thank Omer Edip Erdemli MD, for his assistance in patient care.
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