University of Manchester Rheumatic Diseases Centre and
1 University of Manchester Section of Dermatology, Hope Hospital, Salford M6 8HD, UK
Sir, We report three patients who presented to the Rheumatic Diseases Centre, Hope Hospital, UK with the rare combination of diffuse systemic sclerosis (SSc) and psoriasis, one of whom also had psoriatic arthritis (PsA). In two of the patients there was a temporal relationship between the development of the two conditions, and in both these patients the SSc followed a very aggressive course with rapidly progressive skin involvement. The possible explanations for the co-existence of these two diseases are discussed.
Patient 1. A 54-yr-old female who initially presented to the Dermatology Service in 1993 with an acute onset of pustular psoriasis on the palms and soles. She was treated with the systemic retinoid acitretin. In March 1995 she was referred to the rheumatologists with an 8-month history of Raynaud's phenomenon and diffuse skin thickening over the upper limbs and trunk. On initial investigation, full blood count (FBC) was normal, erythrocyte sedimentation rate (ESR) was 14 mm/h, full biochemical profile was normal and she was negative for antinuclear antibodies (ANA), rheumatoid factor (RF), antibodies to extractable nuclear antigens (ENA) including Scl-70 (topoisomerase) and anti-centromere antibodies. Oesophageal dysmotility and reflux were demonstrated on barium swallow examination and skin biopsy showed dense hyaline sclerosis of the dermis consistent with scleroderma. Nailfold microscopy showed drop-out and dilatation of the capillaries. A diagnosis of diffuse SSc was made. Within 3 months she had developed a renal crisis associated with accelerated hypertension and pulmonary oedema, which responded to aggressive treatment with diuretics and angiotensin converting enzyme (ACE) inhibitors. Since then, renal function has remained stable. Subsequent treatment has included low-dose prednisolone on the assumption that there was a significant inflammatory component to her severe, debilitating skin involvement and regular intravenous prostacyclin infusions. She has continued to have severe psoriasis of the hands and feet requiring in-patient management and topical steroids.
Patient 2. A 43-yr-old male who presented in 1990 with an acute inflammatory polyarthritis involving proximal interphalangeal joints, knees and ankles, with a dactylitis of the right second toe. He had a 2-yr history of psoriasis involving scalp and elbows. Initial investigations, including FBC, ESR (7 mm/h) and full biochemical profile, were normal. He was negative for RF but had positive ANA in a titre of 1/100 with a homogeneous staining pattern. X-rays of the hands, feet and sacroiliac joints were normal. Aspiration of synovial fluid from the left knee revealed a white cell count (WCC) of 2880/mm3 with 73% lymphocytes. A diagnosis of PsA was made, and he was treated with intra-articular steroid injections, followed by sulphasalazine (which was ineffective) and later, D-penicillamine. By 1992, his clinical condition had clearly changed, when he presented with symptoms of Raynaud's phenomenon associated with tightening of the skin, and dysphagia. On examination he had diffuse scleroderma affecting the face, upper and lower limbs. Antibodies to Scl-70 were positive. Nailfold microscopy was normal. Oesophageal reflux was demonstrated on barium swallow. Due to his rapidly progressive skin disease, in January 1995 his penicillamine was stopped and he was entered into the UK randomized controlled trial of alpha-interferon, where he remained on placebo for 12 months. Since then his skin thickening has remained stable. However, he has required non-steroidal anti-inflammatory drugs (NSAIDs) and occasional intra-articular steroids for the PsA.
Following these initial observations, we searched the records of all patients with diffuse SSc, to determine whether any had co-existent psoriasis. The diagnoses of all patients seen at the Rheumatic Diseases Centre, Hope Hospital are recorded on a standardized database, and we found one additional patient listed as having both conditions.
Patient 3. A 63-yr-old female who was referred from another rheumatological unit in 1994 with a 10-yr history of scleroderma involving the face, trunk and limbs. She gave a history of scalp psoriasis since childhood for which she had seen a dermatologist. Investigations, including FBC, ESR, full biochemical profile, RF, ANA, antibodies to ENA, anti-centromere antibodies and nailfold microscopy were all normal. She had a restrictive defect on pulmonary function tests. She has remained well with no deterioration in skin thickening.
We have reported three patients who had the unusual combination of diffuse SSc and psoriasis, one of whom also had PsA. There are only two reported cases of the co-existence of psoriasis and SSc in the English literature [1, 2], one of whom had PsA [1]. A further three cases have been described in Russian [3, 4]. However, psoriasis has been occasionally reported in conjunction with Raynaud's phenomenon [5] and connective tissue disorders including systemic lupus erythematosus (SLE) [6], morphoea and a sclerodermoid variant of mixed connective tissue disease (MCTD) which was interestingly found in a pair of identical twins [7]. There are three possible explanations for this observation. First, it may have occurred by chance. Second, both diseases may share a common aetiology, and third, the presence of psoriasis may have triggered the development of SSc.
With respect to the association being due to chance, 57 patients with SSc who have diffuse skin involvement are currently attending the Rheumatic Diseases Centre. However, it is rare for patients to present with early, aggressive diffuse SSc and it was therefore unusual for two such patients presenting within a short time period to have concomitant psoriasis, a fact which drew a possible association to our attention. Of the 57 patients attending with diffuse SSc, three (5.3%) are listed as having psoriasis. This figure is higher than the reported UK prevalence of 13%. Further, it is likely that the actual frequency of psoriasis in our patients will be higher than this, since we did not specifically set out to look for it. However, we realize that we cannot exclude the possibility that these conditions occurred together by chance.
The second possible explanation is that the two conditions may share a common aetiology. A link between psoriasis and autoimmunity is suggested by the higher than expected prevalence of ANA in patients with psoriasis, particularly after exposure to ultraviolet light [8]. It has been suggested that both psoriasis and autoimmune diseases including SSc may result from a common underlying defect in the immune system [5]. It is therefore interesting to note that both conditions share certain pathological features, such as dermal inflammation, abnormalities of vascularization, acro-osteolysis and possibly abnormalities of the nailfold capillaries.
Previous studies have noted the presence of specific autoantibodies directed against core proteins of heterogeneous nuclear ribonucleoproteins (RNP) in a patient with SSc and PsA [1], and against U1 and U2 small RNPs in two patients with psoriasis and Raynaud's phenomenon [5]. These autoantibodies were not found in sera of patients with psoriasis, Raynaud's or SSc alone, and it was suggested that they may be associated with the development of a distinct form of connective tissue disease [5]. Although we were not able to test specifically for these autoantibodies, none of our three patients had antibodies to U1 RNP, nor had a speckled pattern of ANA staining.
A common genetic background may explain the association, as suggested by the presence of both psoriasis and a sclerodermoid variant of MCTD in two identical female twins [7]. Molta et al. [9] performed full HLA typing on two extended pedigrees which included family members with a wide variety of connective tissue and immunological disorders, including SSc, psoriasis and PsA. However, they were unable to find any common underlying HLA phenotype. The results of HLA typing in our patients was also unhelpful (patient 1: A2, B44 B62, DRB1*0404 0701; patient 2: A2 A3, B7 B18, DRB1*11). It is perhaps more likely that any underlying genetic association is explained by non-HLA genes, for example those involved in cytokine production.
Finally, it is possible that the psoriasis, or its treatment, may have triggered the development of SSc, presumably in a susceptible host. A variety of immunological changes have been well described in patients with psoriasis. Both psoriasis and SSc are predominantly characterized by skin involvement, and it could be hypothesized that the skin abnormalities in psoriasis may have altered the passage and processing of foreign antigen through the skin, thus triggering the development of scleroderma. In patient 1 (and to a lesser extent, patient 2), the development of psoriasis was followed closely by the development of an aggressive form of SSc, which suggests that the psoriasis may have had some role in triggering the SSc. These hypotheses remain speculative, and we would value any further suggestions as to how these conditions may be linked, and whether others have seen similar patients.
Notes
3 Correspondence to: B. Harrison.
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