Erosive osteoarthritis, psoriatic arthritis and pseudogout; a casual association?

DOI 10.1007/s10067-015-2927-9 CASE BASED REVIEW Erosive osteoarthritis, psoriatic arthritis and pseudogout; a casual association? Ariela Hoxha 1 & Amelia Ruffatti 1 & Enrico Alberioli 2 & Mariagrazia Lorenzin 1 & Francesca Oliviero 1 & Elena Mattia 1 & Leonardo Punzi 1 & Roberta Ramonda 1 Received: 12 February 2015 /Accepted: 22 March 2015 # International League of Associations for Rheumatology (ILAR) 2015 Abstract According to recent hypothesis, the inflammation has a pivotal role in the onset and progression of erosive hand osteoarthritis (EHOA), psoriatic arthritis (PsA) and chondrocalcinosis (CC)/pseudogout. Albeit, it has been recognised for years as an association between EHOA and radiographic evidence of CC, but there are few reports of coexistence of microcrystalline arthritis and PsA. This is the first report that described a clinical experience concerning two consecutive cases of patients presented with EHOA, PsA and pseudogout. Two Caucasian women of 71 and 85 years old with a history of OA and mild psoriasis are presented with tenderness and swelling of first interphalangeal (IP) and wrist joint, respectively. Arthrocentesis performed at the first IP and wrist joint, respectively, showed an inflammatory synovial fluid with presence of calcium pyrophosphate dehydrate crystals. X-rays of hands, feet and knees showed characteristic features of EHOA, PsA and CC. Furthermore, HLA typing evinces the presence of HLA C*06; DRB*01 07 and HLA C*07; DRB*01 *11 alleles, respectively, predisposing factors of these inflammatory diseases. The relationship between these aggressive rheumatic diseases along with their clinical, radiographic, laboratory and genetic features is discussed. Keywords Chondrocalcinosis. Erosive hand osteoarthritis. Osteoarthritis. Pseudogout. Psoriatic arthritis * Ariela Hoxha arielahoxha@hotmail.com 1 2 Rheumatology Unit, Department of Medicine DIMED, University of Padua, Via Giustiniani, 2, 35128 Padova, Italy Department of Medicine, Section of Radiology, University of Padua, Via Giustiniani, 2, 35128 Padova, Italy Introduction Erosive hand osteoarthritis (EHOA), an uncommon variant of osteoarthritis (OA), is a prevalent, complex, disabling disease of the joints, characterised by inflammation and degeneration of the distal and proximal interphalangeal (IP) joints with subsequently degradation of the hyaline articular cartilage, erosions and remodelling of the subcondral bone with sclerosis and osteophyte formation leading to joint failure [1, 2]. Psoriatic arthritis (PsA), on the other hand, is an inflammatory arthritis, associated with psoriasis, which over the skin involvement target the spine, the peripheral joints and the entheses [3 5]. PsA can lead to destructive bone loss, and 67 % of PsA patients exhibit signs of erosive bone disease [3]. Pseudogout is an acute manifestation of chondrocalcinosis (CC); this latter is characterised by the deposition of calcium pyrophosphate dehydrate (CPP) crystals and calcification in X-rays [6]. The most commonly affected sites are knees, wrists, and symphysis pubis [6]. According to recent hypothesis [7], inflammation has a pivotal role in the onset and progression of all these diseases. In particular, EHOA called Binflammatory arthritis^ by Ehrlich [8, 9] focused on its inflammatory aspects. However, not all investigators agree that EHOA is a nosologic entity apart from the classic HOA; even some of them consider it a transitional form [10, 11]. Furthermore, PsA is considered the most intriguing inflammatory arthropathy in the differential diagnosis of EHOA [1], as both conditions preferentially affect distal (D) IP joints. Thus, it might be difficult to make the difference by clinical aspects, especially when in PsA, there is an absence of clear skin involvement or there is an exclusive involvement of DIP, as in Bclassic^ variant of Moll and Wright [3]. These assumptions lead to a possible relationship between these diseases. On the other hand, it has been reported [12] that CPP crystals may be found in joint diseases along with previous established

diagnosis. CPP crystals particularly may be found in synovial fluid (SF) of patients with OA who are relatively asymptomatic, as well as, from those who are experiencing an acute flare up of joint pain due to an attack of pseudogout [6]. Sometimes, these forms can be misinterpreted resulting on difficulties in the differential diagnosis. This is a report that describes a clinical experience concerning two consecutive patients presented with EHOA, PsA and pseudogout. The clinical, radiographic, laboratory and genetic features of EHOA, PsA and CC are shown in Table 1. The aim of this report is to evaluate the association and the relationship between these aggressive rheumatic diseases. Materials and methods There are considered two consecutive cases with signs and symptoms common to the EHOA, PsA and pseudogout. The study is carried out in accordance with the principles outlined in the Helsinki Declaration, and all participants gave informed consent. Case 1 A 71-year-old woman with a history of 17 years of OA referred to Rheumatology Unit, University of Padua, with tenderness of first IP joint of the right hand. Physical examination revealed swelling and tenderness of first IP joint of the right hand and tenderness of several proximal (P) IP joints of the hands besides the fifth metatarsal phalangeal (MP) joint of left foot and tarsal-metatarsal (TM) bilateral joints. She referred mild psoriasis of scalp. Arthrocentesis performed at the first IP joint and, surprisingly, showed an inflammatory SF with the presence of CPP crystals as seen in Fig. 1. The X-rays of the hands showed calcifications of the first IP joint and triangular ligament of the carpus, peculiar of CC (Fig. 1). Moreover, marked asymmetric joint space narrowing (JSN), central erosion of the second DIP joints, the so-called gull wing appearance along with osteophytes and sclerosis and central collapse typical signs of EHOA were seen too (Fig. 1). To note, radiopaque deposits in meniscus and marked JSN, with large marginal osteophytes, peculiar of CC and OA were observed in the X-rays of the knees (Fig. 1). Interestingly, X-rays of feet showed characteristic findings of arthritis as symmetric JSN and marginal erosions of the TM joints with ankylosis as seen in Fig. 2. HLA typing, furthermore, evinces the presence of HLA C*06; DRB*01 07 alleles. Diagnosis of EHOA, PsA and pseudogout has been made, and therapy with low-dose methylprednisolone, hydroxychloroquine and colchicines was started. Actually, the patient is recovering quite well, by continuing the therapy with colchicines and low-dose methylprednisolone during arthritis relapses, while hydroxychloroquine has been stopped due to mild impairment of macular pigmentation. Case 2 An 85-year-old woman, known affected by diffuse OA, admitted to Rheumatology Unit, University of Padua, because of acute arthritis of the left wrist. The patient presented appeared with tenderness, swollenness and warmth of left wrist along with high levels of C-reactive protein. Physical examination confirmed the arthritis of the left wrist. Moreover, onicopathy was been observed too. Ultrasound image of the left wrist showed mild intraarticular fluid-containing hyperecogenic foci and marked hypertrophy with hypervascularity of synovial membrane along with hyperecogenicity of triangular ligament. Aspiration joint was performed at the left wrist that showed an inflammatory SF with the presence of extracellular CPP crystals. Calcification of the triangular ligament of the carpus has been seen in the hand X-rays characteristic of CC along with signs of EHOA of DIP and PIP joints (Fig. 3). Surprisingly, characteristic findings of PsA (Fig. 3) such as symmetric JSN, subcondral sclerosis and marginal erosions determining the typically pencil in cup lesion at second and third DIP of the left hand were seen too. Furthermore, HLA typing showed the presence of HLA C*07 and DRB*01 *11 allele. Diagnosis of EHOA, PsA and pseudogout has been made, and therapy with methotrexate 7.5 mg per week, lowdose methylprednisolone and colchicines was started. Actually, the patient is recovering quite well by continuing the therapy with methotrexate and low-dose methylprednisolone, while colchicines has been suspended after 2 days due to diarrhoea. Discussion Albeit, it has been recognised for years as an association between EHOA and radiographic evidence of CC, but there are few reports of coexistence of microcrystalline arthritis and PsA [16, 17]. This is the first report, as far as we know, that documents the co-occurrence of EHOA, PsA and pseudogout. The coexistence of these three different rheumatic disorders leads to assume a possible association or common predisposing condition. Classically, the OA is defined to be a non-inflammatory joint disease, in order to distinguish it from the so-called arthritides, characterised by the presence of an inflammatory arthritis. However, accumulating evidence [2] suggests that inflammation of various types plays a key role in the pathogenesis of OA, as demonstrated by the presence of inflammatory features in the synovial membrane of at least 50 % of patients with OA. The only OA variant proposed and classified as inflammatory is the one of the hand [7, 8]. In fact,

Table 1 Clinical, radiographic, laboratory and genetic characteristics in erosive hand osteoarthritis, psoriatic arthritis and pseudogout EHOA PsA Pseudogout Clinical features Onset Frequently abrupt Moderate/abrupt Silent/abrupt Pain Recurrent and persistent Persistent During acute attack Tenderness Persistent Persistent During acute attack Erythema Frequent, recurrent during the flares Frequent During acute attack Warmth Frequent, chronic, recurrent Frequent, recurrent during flare During acute attack Morning stiffness Frequent (<30 min) Persistent (>30 min) During acute attack Swarming and dysesthesia Possible Sometimes Uncommon Number of joint affected Sometimes more than one simultaneously Oligo and/or poliarthritis Usually monoarthritis Radiographic features Joint involvement DIPs, PIPs All joints (DIPs involvement is Bclassic^ feature) All joints (more frequently knee and wrist) Erosion type Central erosion in the proximal plate and marginal proliferation in the distal plate of DIPs and PIPs Marginal erosions in proximal plate and marginal periostitis in the distal plate at DIPs Uncommon Periarticular osteoporosis Absent Sometimes present Absent Ankylosis Frequent Frequent Absent Periostitis Sometimes Frequent Absent Calcification Absent Absent Present Laboratory features High C-reactive protein Sometimes during flares Frequently During acute attack High erythrocyte sedimentation rate Sometimes during flares Frequently During acute attack Genetic features HLA A23, DRB*01 07, 11 [13] HLA C*6, C*7 [14] SNPs for ANKH [15] EHOA erosive hand osteoarthritis, PsA psoriatic arthritis, DIPs distal interphalangeal joints, PIPs proximal interphalangeal joints, HLA human leucocytes antigens, SNPs single-nucleotide polymorphism, ANKH ankylosis human genes

Fig. 2 X-rays of feet showed tarsal-metatarsal arthritis Fig. 1 Synovial fluid from the first IP joint evinced the present of calcium pyrophosphate crystals (arrowhead), and X-rays of the hand and knees showed characteristic features of EHOA and CC, asymmetric joint space narrowing (squares), central erosion (asterisk) of the second distal interphalangeal joints, the so-called gull wing appearance along with osteophytes and sclerosis (white arrowhead) and central collapse (star), and calcifications of the first IP joint and triangular ligament of the carpus (arrow), respectively marginal periostitis in the distal plate at DIP joints. Another important difference between these two conditions is the periostitis, rare in EHOA, but commonly observed in PsA with a usually Bfluffy^ image at IP joints, and easily distinguished from the linear bony apposition observed in EHOA. Additionally, no acro-osteolysis, pencil-like deformities and arthritis mutilants are found in EHOA. Since in some diseases, it is possible to find erosive changes resembling EHOA, it may be difficult to establish whether these changes are an expression of the same disease or are due to an association with EHOA. These cases are more numerous than might be expected and may be essentially included in many diseases: endocrine diseases such as hypothyroidism and hyperparathyroidism [18, 19]; microcrystal induced arthtritis, such as CPP crystals, apatite crystals and calcific patients with inflammatory hand OA revealed radiographic erosions leading to difficulty in differential diagnosis. Concerning the differences with inflammatory arthropathies, the most intriguing is the one with PsA. Although the main hallmark of EHOA is the presence of DIP and PIP erosions at the X-ray, sometimes, the differentiation by the PsA hand could be debated. As shown in Table 1, both conditions preferentially affect DIP joints, and clinical aspects may be difficult to make the difference, especially when in PsA, there is an absence of clear skin disease or an exclusive involvement of DIP joints. In most cases, radiographs are useful in resolving any doubts. Particularly, in EHOA, the erosions have a gullwing appearance characterised by central erosion in the proximal plate and marginal proliferation in the distal plate of DIP and PIP joints, while in PsA, the erosions have a mouse-ear configuration due to marginal erosions in proximal plate and Fig. 3 X-rays of hand showed radiologic feature of erosive hand osteoarthritis, psoriatic arthritis and chondrocalcinosis. Calcification of the triangular ligament of the carpus (arrow), asymmetric joint space narrowing (squares), the so-called gull wing appearance along with osteophytes and sclerosis (white arrowhead), marginal erosions (white star) pencil in cup lesion at second and third DIP of the left hand (asterisk) and cystic erosion of styloid apophyses (black star)

periarthritis associated with hypophosphatasia [20], chronic renal diseases [21, 22], autoimmune diseases such as scleroderma [23], Sj gren s syndrome[24] and autoimmune thyroiditis [25]. Some of these combinations are probably only anecdotal; however, they may be useful in better understanding the differential diagnosis of EHOA by other diseases and their likely associations. Since these coincidences are rarely reported, we wanted to describe, instead, the curious associations between EHOA, with PsA and pseudogout in two consecutive patients. We observed in our patients the presence of some alleles that is usually described in EHOA and PsA, particularly HLA C*06 DRB*1 07 and HLA C*07 DRB*01 11, respectively, that are found in the former and in the latter patient. Previously, this type of alleles were reported in PsA (C*06 and C*07) and EHOA (DRB*01 07 and DRB*01 11) [13, 14]. Probably, their coexistence in these patients suggests that the underneath genetic predisposition plays a crucial role in the pathogenesis of these diseases. In fact, recent studies [13 15] found a significant prevalence of alleles characterising an immunogenetic predisposition to autoimmunity in patients with rheumatic diseases described. So, another point to debate could be linked to the autoimmune disorder frequently highlighted on these diseases [13 15]. However, these hypotheses should be regarded with caution, due to the higher frequency of both autoimmune diseases and EHOA in women, as in our report cases, and such association might only be casual. Prospective, multicentre, large-scale studies will be necessary to clear up these considerations. In conclusion, it is important to take into account this association when facing the patients for a correct diagnosis and appropriate treatment. 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