Case Report: Hajdu-Cheney Syndrome

The rest of his laboratory testing results were unremarkable: His HLA-B27 was negative, as were his anti-nuclear antibody (ANA) titers and rheumatoid factor levels. Other serologies, including antibodies against cyclic citrullinated peptide (CCP), SSA/Ro, SSB/La, nuclear ribonucleoprotein (RNP), Smith antigen and double-stranded DNA were negative. Additionally, C3 levels, C4 levels and ferritin levels were within normal limits, and HIV was non-reactive.

X-rays of both hands showed acro-osteolysis of the distal phalanges of all digits. X-rays of both feet showed soft tissue calcinosis and resorption of the distal phalanges (see Figures 2 and 3).

Electromyography (EMG) showed a partial radial mononeuropathy in the right upper extremity, distal to the spiral groove. Preservation of the distal motor amplitude suggested favorable prognosis for spontaneous recovery; however, there was a mild distal axonal sensory peripheral polyneuropathy. Of note, a 9–10 Hz tremor was observed in several muscles.

Discussion

When we saw this patient, we investigated rheumatic etiologies for acro-osteolysis, especially given the pains he was experiencing; however, our workup was nonrevealing. Given the patients severe osteoporosis, the suspicion of HCS was high. His pain, swelling and neuropathic symptoms were likely secondary to HCS.

FIGURE 3: Left foot X-ray shows calcinosis in the

second distal phalanx and resorption of distal phalanges. (Click to enlarge.)

Acro-osteolysis can occur in a variety of conditions, but rheumatologists are most likely to encounter acro-osteolysis in systemic sclerosis and psoriatic arthritis. It can also be found in rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), systemic lupus erythematosus (SLE) and Sjögren’s disease.¹ Acro-osteolysis can occur in up to 65% of patients with systemic sclerosis, depending on the definition and the sensitivity of the confirmatory imaging modality.² The pathophysiology in scleroderma appears to be related to microangiopathy causing hypoxia and leading to bone resorption and remodeling.⁶

Regarding psoriatic arthritis (PsA), a case series found three of 47 patients had acro-osteolysis.⁵ Psoriatic arthritis involves erosive changes in the distal extremity joints and the chronic inflammation associated with PsA is thought to cause the bone destruction found in acro-osteolysis.³

In RA, GPA, SLE and Sjögren’s disease, acro-osteolysis has been described in case reports.

Non-rheumatic etiologies of acro-osteolysis include occupational exposure, bacterial infections, hyperparathyroidism, diabetes mellitus type 1, lysosomal disease and other genetic disorders, such as Gaucher’s disease.^2,4

Diagnosis of HCS includes genomic sequencing. Current investigational treatments are osteoporotic medications, but it is unclear if these are helpful.¹ Our patient was offered zoledronic acid, but he was lost to follow-up.