Acrocyanosis stems from Greek word which literally means bluish (kyanos) discoloration of the extremities (akron). First coined by Crocq in 1986, acrocyanosis is a part of acrosyndromes together with Raynaud’s phenomenon and erythromelalgia. It refers to persistent abnormal deep blue or cyanotic discoloration of skin over the extremities (hand and feet most commonly) due to decreased oxyhemoglobin secondary to vasospasm. Acrocyanosis usually presents with coolness and violaceous dusky discolorations of hands and less frequently the feet.(1) Other peripheral parts like ear, nose, lips, and nipple can also be affected. It is marked by symmetry and aggravated by exposure to cold, and frequently associated with local hyperhidrosis of hands and feet.(2) Its prevalence remains unknown due to scarcity of reported cases.(1)
Acrocyanosis can be divided into primary and secondary acrocyanosis according to the absence or presence of causative factors. Primary acrocyanosis is not associated with an identifiable cause and is usually benign with a good prognosis in which ulceration and tissue loss are extremely rare. In primary acrocyanosis, there is no associated pain and patients are normally asymptomatic aside from discoloration. Trophic skin changes and ulceration are not seen except in remittent necrotising acrocyanosis. It is also associated with enhanced susceptibility to cooling and pain, as well as ulceration and gangrene of the fingers(1). Secondary acrocyanosis is associated with other conditions and may lead to ulceration and necrosis. This includes hypoxaemia, cardiovascular disease, thromboembolism, haematological disorder, toxic exposures, and drug induced.(3)
Investigations for acrocyanosis include meticulous history taking and clinical examinations to determine the possible aetiology. Capillary oximetry that shows normal oxygen saturation rules out vaso-occlusive disease. Other laboratory investigations and imaging studies are needed to identify the aetiology of secondary acrocyanosis depending on the clinical signs and symptoms of underlying disease in individual cases. Complete haemogram is essential for lymphoproliferative disease and essential thrombocythemia. Screening for connective tissue disease and antiphospholipid antibody syndrome is compulsory. Metabolic screening may be required for fucosidosis in suspected cases. In addition, CT scan, MRI, and nerve conduction study may be required to rule out any underlying neoplastic disease, spinal cord injuries, thromboembolism, and nerving plexus neuropathy.(1) When cutaneous vasculitis is suspected, skin biopsy is the gold standard investigation to confirm the diagnosis.(4) Drug-induced acrocyanosis have been observed with certain drugs such as selective serotonin reuptake inhibitors, tricyclic antidepressants, norepinephrine, clonidine, interferon, alphaprodine, amphotericin B, and intra-arterial injection of propoxyphene. Intravenous chemotherapy with gemcitabine, cisplatin or oxaliplatin have also been reported to cause acrocyanosis.(1) Other drugs known to induce acrocyanosis are metoclopramide, imipramine, desipramin, and fluoxetine.(5) To the best of our knowledge, this is the first reported case of diclofenac-induced acrocyanosis.
In this case, our patient presented with acrocyanosis secondary to drug-induced cutaneous vasculitis, which was confirmed on skin biopsy showing lymphocytic vasculitis. Lymphocytic vasculitis is more common in connective tissue diseases, viral infections and drug eruptions.(4) Unfortunately, our patient’s condition progressed to develop digital gangrene. The pathophysiology of inflammation induced thrombosis is complicated. Thrombosis is a well-known association with systemic vasculitis, however thrombosis in small vessel vasculitis is comparatively rare.(6) Hyperactivation of the coagulation system along with the impaired activation of the fibrinolytic system may explain the thrombosis formation.(6) Damage to the endothelial cells, induced oxidative stress along with hypercoagulability states will further lead to gangrene and amputations of the limbs in the majority of the cases.(3) Symptoms of toe gangrene in our patient improved initially with steroids and anticoagulation. However, the progression to toe necrosis were unsalvageable. Transmetatarsal amputations were performed as the final resolution to resolve the persistent toes infection.
Treatment for secondary acrocyanosis involves mainly by treating the underlying cause.(1) In severe cases, drugs like calcium channel blocker (CCB) and alpha-adrenergic blocking agents (prazosin) can be used in view of vasodilatory action of these drugs. Trial of combination of pentoxifylline and diltiazem in remittent necrotising variety also had been shown to have good results in primary acrocyanosis.(1) In cases of cutaneous vasculitis, in some instances, it may require only symptomatic management as the process may be self-limited after removing the potential trigger. However, at present, the evidence-based guide to treat cutaneous vasculitis is limited due to the varying types of vasculitis affecting the skin and is mainly based on case series and experts opinion.(7) The choice of treatment will depend on the severity of the vasculitis. Systemic corticosteroids (0.5-1mg/kg) has been used in IgA/IgM immune complex vasculitis to achieve rapid resolution and can safely be tapered slowly over 3–6 weeks. However, due to high risk of relapse with rapid tapering, those with chronic or recurrent disease or flare while tapering down steroids, other steroid-sparing agents had been used including colchicine, dapsone and azathioprine.(7)