A case of exuberant acroosteolysis and subcutaneous tissue calcinosis in the absence of skin involvement is presented. Different hypotheses are discussed following the clinical unfolding of the case in practice

Ambrósio, C

Malcata, AB

Matucci-Cerinic, M

Pereira da Silva, JA

Saavedra, MJ

Repositório Institucional dos Hospitais da Universidade de Coimbra

S-551Serviço de Reumatologia, Hospitais da Universidade de Coimbra, Portugal;2Department of BioMedicine, Denothe Center, Division of Rheumatology, University of Florence, Italy.Maria João Saavedra, MDCatarina Ambrosio, MDArmando Malcata, MDMarco Matucci-Cerinic, MD, PhDJosé Antonio P. Da Silva, MD, PhDPlease address correspondence to: Marco Matucci-Cerinic, Department of Biomedicine, Division of Rheumatology, Villa Monna Tessa, viale Pieraccini 18, 50139 Firenze, Italy, E-mail: cerinic@uniﬁ.itReceived on June 25, 2009; accepted in revised form on July 17, 2009.Clin Exp Rheumatol 2009: 27 (Suppl. 54): S55-S58.© Copyright CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 2009.Key words: Acroosteolysis, calcinosis, systemic sclerosis, skin involvement.Competing interests: none declared.ABSTRACTA case of exuberant acroosteolysis and subcutaneous tissue calcinosis in the absence of  skin involvement is present-ed. Different hypotheses are discussed following the clinical unfolding of the case in practice. IntroductionAcroosteolysis and calcinosis are a ne-glected problem in rheumatic diseases. We herein discuss and analyse a case presented over three vignettes.Case vignette I  A 71-year-old female, presented with bilateral arthralgia and swelling of the wrists, MCPs, PIP, DIP and MTP joints evolving with variable intensity for ﬁf-teen years. She described typical bilat-eral Raynaud’s phenomenon over the past four years, but denied any other relevant signs or symptoms.The joints were tender and presented bony nodules that were inﬂamed over the right elbow and ankle. Facial tel-angiectasias (Fig. 1) were noted and no ﬁbrosis was detectable on the hands (Fig. 2). General examination was normal.X-rays revealed acroosteolysis in the hands (Fig. 3A)  the knees, feet and Achilles tendon (Figs. 3B, C, D).DiscussionAcroosteolysis consists of the resorp-tion of bone extremities, more fre-quently the distal phalanxes. It may be part of primary familial syn-dromes, which tend to follow an auto-somal hereditary pattern. Acroosteoly-sis of distal phalanxes is usually found in all these conditions (Table I) but may also be accompanied by other bone modiﬁcations not seen in our patient. Acroosteolysis may also develop as a result of local repetitive trauma (ther-mal, electrical and mechanical) or pe-ripheral ischemia. It has been reported to affect 1 to 3% of people chronically exposed to vinil chloride (9).It has been described in association with a variety of cutaneous diseases (psoriasis, leprosy, bullous epidermoly-sis, cutaneous porphiria, síﬁlis and pit-iríasis rubra), metabolic diseases (gout, hyperparathyroidism, osteomalacia and diabetes mellitus) and neurological conditions (syringomyelia and sympa-thetic reﬂex dystrophy). Occasionally, acrosteolysis has been interpreted as a secondary manifestation to tumours, such as lung cancer, Sésary’s syndrome and lymphoma (9). Case reportExuberant calcinosis and acroosteolysis. A diagnostic challenge M.J. Saavedra1, C. Ambrosio1, A. Malcata1, M. Matucci-Cerinic2, J.A.P. Da Silva1Fig. 2.  The digits did not present edema or ﬁbro-sis; the skin can be pinched without any problem.Fig. 1. Teleangectasias are visible on the face of the patient.S-56CASE REPORT Exuberant calcinosis and acroosteolysis / M.J. Saavedra et al.More commonly, however, acrosteoly-sis is observed in patients with con-nective tissue diseases, with special emphasis on systemic sclerosis (SSc). However, patients with systemic lupus erythematosus, mixed connective tis-sue disease, Sjögren’s syndrome, rheu-matoid and psoriatic arthritis and sar-coidosis can also present resorption of distal and proximal phalanxes (9-11). Tissue calcinosis (deposition of insolu-ble calcium salts in soft tissues) can oc-cur as a result of hypercalcemia, usually in the context of hyperparathyroidism. In idiopathic conditions, with normal circulating levels of calcium and phop-shorus, nodular or milia-like deposits of calcium salts are found in the subc-taneous tissue (more commonly of the head or the extremities, the scrotum or the periphery of joints). This situation affects young people or patients with Down’s syndrome (12-13). However, in the absence of serum cal-cium abnormalities, calcinosis usually affects sites of previous lesions. This so called “dystrophic calcinosis” can be found in tumours and sites of trauma or infection but also in scarring tissue of patients with SLE, systemic sclero-Fig. 3 A. Acroosteolysis of distal phalanges and extensive calcinosis are visible; B, C, D: calcinosis of the Achilles tendon, feet and knee are visible.ABC DTable I. Hereditary syndromes causing distal phalanx osteolysis (1-8). Condition Hereditary pattern Age at onset Additional clinical featuresHadju-Cheney’s syndrome Dominant autosomal Infancy Cranial and facial anomalies; premature loss of teeth and    micrognathia; short statureMandibuacral syndrome Recessive autosomal Adolescence/young Mandible and clavicle hypoplasia; cutaneous atrophy;   adulthood lipodistrophySchinz disease Dominant autosomal Adolescence/ young Recurrent ﬁnger ulcerations   adulthood Neurogenic acroosteolysis Dominant or recessive Childhood Sensorial neuropathy; Mal perforans; vasomotor disfunction;  autosomal   hyperhydrosisWerner’s syndrome Recessive autosomal Adolescence/ young Precocious ageing; wrinkled skin; baldness; cataracts; muscular   adulthood atrophy; diabetes mellitusPachydermoperiostsis Recessive autosomal Adolescents/adults Finger clubbing, Periostosis, arthritis, seborrhoea, cutis(primary hypertrophic    verticis gyrateosteoarthropathy)S-57CASE REPORTExuberant calcinosis and acroosteolysis / M.J. Saavedra et al.sis, dermatomyositis, mixed connec-tive tissue disease and Ehler-Danlos syndrome (12-16). In summary, potential causes of con-comitant acroosteolysis and tissue cal-cinosis appear to be limited to systemic sclerosis, SLE, mixed connective tissue disease and hyperparathyroidism.Case vignette II   Laboratory evaluation showed normal full blood count and urinalysis, nor-mal C-reactive protein (0.14mg/dl) and raised ESR (36mm). Serum calcium (9.4g/dl), phosphorus (3.7mg/dl), al-bumin (4.0g/dl), alkaline phosphatase (70U/L), parathormone (73.6 pg/ml) and thyroid hormones were all within the normal range.Chest x-ray revealed a reticular pattern suggesting interstitial ﬁbrosis (Fig. 4). Hyperparathyroidism may be excluded on the basis of normal serum and urine calcium and phosphate, as well as se-rum parathormone. However, clinical criteria were missing for any connec-tive tissue diseases.Acroosteolysis makes SSc a major di-agnostic hypothesis corroborated also by calcinosis. The major problem with this diagnosis in the present case is the absence of skin involvement and the late onset of Raynaud’s phenom-enon. The patient did not present other symptoms or signs that would rein-force this hypothesis, such as dyspnea or dysphagia. The patient did not satisfy the ACR criteria for SSc classiﬁcation which require the ﬁnding of either the sole major criterion (SSc proximal to meta-carpophalangeal or metatarsophalan-geal joints) or two or more of the minor criteria (sclerodactily, digital pitting scars, bibasilar pulmonary ﬁbrosis) (17). Only one of the minor criteria was present in this case. Limitations of ACR criteria have been pointed out, especially regarding lack of sensitivity in limited cutaneous SSc subset (18). Abrams et al. described for the ﬁrst time in 1954 a rare form of SSc (19) characterized by the presence of viscer-al manifestations without skin changes. The term SSc sine scleroderma (SSss) was coined in 1962 by Rodnan e Fen-nel (20). The largest case series, was published in 2000 (21) and included 48 cases of SSss representing 9% of 555 SSc patients. Based on this series, the authors proposed a set of diagnostic criteria for SSss (Table II).Further investigations of our patient show that she satisﬁes these criteria. Case vignette IIIIgG rheumatoid factor (47 UI/ml, nephelometry), antinuclear antibodies (1:640 speckled and nucleolar pattern) and SSA were positive.While anti-cen-tromere, anti-topo I or anti-RNP anti-bodies were negative. Chest high-resolution CT-scan revealed areas of ground-glass in the lower lobes (Fig. 5). Respiratory function tests re-vealed a reduced alveolar diffusion (DLCO/ VA – 66.6%). Oesophageal ma-nometry was normal. Cardiac echocar-Fig. 4.  Chest x-ray shows a reticular pattern.Table II. Diagnostic criteria for systemic sclerosis sine scleroderma according to Poormoghim (21).1. Raynaud’s phenomenon or peripheral vascu-lar equivalent (digital pitting scars, digital-tip ulcers, digital-tip gangrene or abnormal nail-fold capillaries)2. AND3. Positive antinuclear antibodies 4. PLUS one or more of the followinga. Distal oesophageal hypomotilityb. Small bowel hypomotility c. Pulmonary interstitial ﬁbrosisd. Primary pulmonary arterial hypertension (without ﬁbrosis)e. Renal failure consistent with scleroderma renal crisis f. Cardiac involvement typical of SS5. Absence of any other connective tissue dis-ease as a cause of 1, 2 or 3. Fig. 5. Chest high resolution computed tomo-graphy shows the ground glass of lower lobes.Fig. 6. Nailfold videocapillaroscopy: the pattern shows an avascular area. Table III. Clinical and serologic comparison between SSc sine scleroderma and limited SSc according to Poormonghim (21). SSss lcSSANA 94% 94%Anti-centromere  31% 54%Anti-RNA polymerase III 6% 1%Other non-SSc associated antinuclear antibodies 44% 14%Pulmonary involvement 68% 65%Primary pulmonary arterial hypertension (PPAH) 23% 13%PPAH as cause of death 52% 24%S-58CASE REPORT Exuberant calcinosis and acroosteolysis / M.J. Saavedra et al.diography did not detect increase in mean pulmonary pressure.Capillaroscopy showed dysmorphic capillaries, megacapillaries, avascular areas and haemorrhages (22) (Fig. 6). Poormonghim’s series suggests that anti-centromere antibodies are less fre-quent in SSss than in the typical limited SSc subset, whereas other antibodies usually not related to SSc are more fre-quently present (Table III). The preva-lence of pulmonary hypertension was higher in the SSss being the most fre-quent cause of death. In 2002, Slobodin et al. (23) suggested the recognition of two different types of SSss. Some patients present with Raynaud’s phenomenon, oesophageal dysmotility and antinuclear antibod-ies in the absence of previous connec-tive tissue disease of any sort. Such cases, which represented the majority of Poormoghim’s series, could be seen as incomplete forms of limited SSc and had a good prognosis. In other patients, features of SSss develop in the context of a previous undifferentiated connec-tive tissue disease. This condition may be associated with a more aggressive course and SSc can be expected to ap-pear in up to 60% of cases in the ﬁrst 7 years. This latter pattern could be seen as SSc before (rather than sine) the onset SSc.Our case seems to ﬁt best in the ﬁrst pattern even if it does not fulﬁl the ACR SSc criteria (17, 18). Although SSc is a lethal disease (24), the visceral involvement can be considered benign until now. This is in contrast with a very aggressive arthritis and exquisite-ly exuberant calcinosis and acroosteol-ysis, without skin involvement, twelve years after the onset of  ﬁrst symptoms of disease.It is interesting to note that, in our pa-tient, Raynaud’s phenomenon started eight years after the proven onset of acroosteolysis. This would question the view according to which acroosteoly-sis in SSc is an ischemic consequence (10). Calcinosis has been proposed as a potential factor for acroosteolysis through induction of subchondral bone infarction (9, 10).In conclusion, this case points out the importance of acroosteolysis and cal-cinosis as two important clinical signs that should induce  the clinician to care-fully analyse the whole case in order to best perform the differential diagnosis in the ﬁeld of rheumatic, metabolic and congenital diseases.  References   1.  SZOKE G, VIZKELETY TL, RÉNYI-VÁMOS A, ELEK E: Idiopathic carpotarsal osteolysis with Bartter’s syndrome. 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Exuberant calcinosis and acroosteolysis. A diagnostic challenge

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Exuberant calcinosis and acroosteolysis. A diagnostic challenge

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