Introduction

Acquired clubbing of the digits andhypertrophic osteoarthropathy(HOA) are closely related disordersof unknown aetiology that may oc-cur in a number of underlying dis-eases of the thorax and abdomen.HOA is characterised by the concur-rence of digital clubbing, periostitisof the long bones and arthritic symp-toms in the wrists, elbows, knees andankles. A clinical diagnosis of digitalclubbing is based on the finding ofan increase in the soft tissues at thebase of the finger or toe-nails. Bonescintigraphy has emerged as themost sensitive test for HOA [1].

HOA without clubbing appears tobe unusual, with only two previousreports in a Medline search of theworld literature [2, 3]. In such pa-tients, the diagnosis of HOA may beoverlooked. We present two furthercases of HOA without digital club-bing. In addition, one of the casesalso demonstrated scintigraphic evi-dence of periostitis of the metacarpaland metatarsal bones, an entity thathas not been reported previously.

Case reports

Two male patients aged 64 and73 years presented with painful

wrists, knees and ankles. Both pa-tients were heavy cigarette smokers,consuming 20–40 cigarettes per dayfor over 30 years. Physical examina-tion revealed no evidence of digitalclubbing in either patient. Diffuseperi-articular tenderness was presentaround the wrists, knees and ankleswithout clinical synovitis. Radiologi-cal investigations led to the diagno-sis of lung carcinoma in both pa-tients, confirmed to be non-smallcell cancers on biopsy. Bone scintig-raphy was undertaken in both pa-tients for suspected metastatic dis-ease and further evaluation of thejoint symptoms. This revealed a pat-tern of uptake characteristic of HOA

Received: 22 March 2001Revision accepted: 23 May 2001Published online: 22 September 2001© ISS 2001

Abstract Hypertrophic osteoar-thropathy (HOA) typically occursconcurrently with clubbing of thedigits, with isolated HOA being re-ported only rarely. We report two pa-tients with intra-thoracic malignancyin whom HOA, demonstrated onbone scintigraphy, developed in theabsence of clubbing. We also reportthe novel observation of involvementof the metatarsal and metacarpalbones by HOA.

Keywords Hypertrophic osteoarthropathy · Clubbing · Bonescintigraphy

Skeletal Radiol (2001) 30:652–655DOI 10.1007/s002560100404 C A S E R E P O RT

Stephen ClarkeLeslie BarnsleyMatthew PetersLucy MorganHans Van der Wall

Hypertrophic pulmonary osteoarthropathywithout clubbing of the digits

S. ClarkeDepartment of Oncology, Concord Hospital, Sydney, Australia

L. BarnsleyDepartment of Rheumatology, Concord Hospital, Sydney, Australia

M. PetersDepartment of Respiratory Medicine, Concord Hospital, Sydney, Australia

L. MorganDepartment of Nuclear Medicine, Concord Hospital, Sydney, Australia

H. Van der Wall (✉ )Department of Nuclear Medicine, Concord Hospital, Concord 2139, Australia

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Fig. 1 Case 1. Anterior whole body image. Moderate intense para-cortical uptake ispresent in the femora, tibiae and around the wrists. These are the characteristic appear-ances of HOA. Degenerative changes are seen in the shoulders, knees and hips. No fo-cal abnormality is present to indicate metastatic bone disease

Fig. 2 Case 1. Hands and feet. Limited photographic views of the hands and feet donot show evidence of digital clubbing. Regional views of the bone scan study showpara-cortical increase in uptake in several metacarpal and metatarsal bones (arrows)but no increase in uptake at the tips of the digits, as would occur in clubbing

Fig. 3 Case 2. Anterior and posterior whole body image. Intense para-cortical uptakeis present in the femora, tibiae and around the wrists. These are the characteristic ap-pearances of HOA. Degenerative changes are seen in the shoulders, knees and hips. Nofocal abnormality is present to indicate metastatic bone disease

Fig. 4 Case 2. Hands and feet. Limited photographic views of the hands and feet donot show evidence of digital clubbing. Regional views of the bone scan show no in-crease in uptake at the tips of the digits, as would occur in clubbing

(Figs. 1, 2) in both patients. Region-al views of the hands and feet(Figs. 3, 4), however, did not revealthe characteristic scan features ofdigital clubbing. Neither patient wasthought to have scintigraphic evi-dence of metastatic disease.

Discussion

Over 90% of the cases of HOA inadults occur in patients who eitherhave, or will develop, a malignancy[4]. The most frequently associatedtumour is non-small cell carcinomaof the lung [5]. Regardless of theaetiology, there is clearly a linkagebetween clubbing and HOA, withmany authors postulating a singlepathological process giving rise toboth entities, HOA being a more se-vere manifestation [6]. This linkageis well established enough for theoccurrence of HOA in the absence ofclubbing to be reported on a few oc-casions, commencing in 1947 [3].The cases presented on this occasionare similar, except for the periostealinvolvement of the metacarpal andmetatarsal bones in one of the cases.This observation is unique and hasnot been reported in the extant litera-ture, encompassing patients withHOA with or without digital club-bing. The common pathway of pa-thology is thought to be bony remod-elling at the tips of the digits withtuft hypertrophy and osteolysis [7] aswell as irregular deposition of can-cellous bone on predominantly thelateral edges of the long bones [8].This produces the scintigraphic ap-pearance of predominantly sub-peri-osteal increase in uptake in the longbones and increased uptake at thetips of the digits, at the sites of club-bing.

The underlying mechanism ofclubbing and HOA is not known.However, a number of plausible the-ories have been advanced [9]. Theseinclude the megakaryocyte/plateletclump hypothesis, increased plateletderived growth factors, vascular en-dothelial growth factor [10] and

growth hormone. A simple distilla-tion of these complex theories mayyield a plausible explanation for thetwo cases under discussion.

Theories of causation of HOAmay be divided into the predomi-nantly mechanistic or biochemicalcategories. The mechanistic theoriesare based on arteriovenous shunting,as in some cyanotic heart lesions andin severe cirrhosis (where arteriove-nous connections have been demon-strated in the lungs) [11]. Conse-quently, vasoactive compounds nor-mally inactivated in the lungs reachthe systemic circulation. Normally,megakaryocytes are transported tothe lung in the venous circulationfrom the bone marrow and fragmentin the pulmonary capillaries, leadingto the release of platelets [12]. Ifthere is significant shunting of bloodin the lungs, megakaryocytes escapethe filtering effect of the pulmonarycapillaries and reach the systemic ar-terial circulation. They may then im-pact in the peripheral tissues of thedigits, leading to degranulation andthe production of platelet derivedgrowth factors (PDGF), causing dig-ital clubbing. In these cases, digitalclubbing is more pronounced withmilder or absent HOA. It is also possible that there is a significant de-gree of shunting of blood in primarylung carcinomas, producing a simi-lar effect to other forms of shunting[9].

Biochemical theories of HOA andclubbing suggest that some forms ofchronic lung suppuration may pre-dispose to platelet aggregation andthrombosis in veins draining the in-flamed areas as well as lowering thethreshold for peripheral activation[13]. Thus, peripheral activation ofsuch platelets may lead to clubbing.Platelet function may also be alteredin carcinoma of the bronchus [14], asmegakaryocytes are larger than nor-mal and may contain increasedPDGF synthetic activity. Other fac-tors such as growth hormone secre-tion by bronchial carcinoma havealso been implicated in the occur-rence of HOA and clubbing [15].

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It is conceivable that in our casesthe potential for clubbing was lessdue to the absence of significant tu-mour shunting. However, the abilityto secrete appropriate growth factorswas retained, producing the scinti-graphic features of HOA.

Conclusion

These two cases demonstrate the un-usual finding of HOA in the absenceof digital clubbing in patients withnon-small cell cancer of the lung.Although the aetiology of clubbingand HOA remains obscure, at leasttwo major theories have been ad-vanced to explain the linkage. A dis-junction between the biochemicaland mechanistic theories may ex-plain this phenomenon in these twocases.

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