Congential

In infants, cutis marmorata is physiologic LR which responds to rewarming and may be localized or generalized. Cutis marmorata telangiectatica cutis (CMTC) is LR that appears at birth, may not respond to rewarming, and may have associated abnormalities

Vasospasm

The most common cause of LR, which is often seen in association with autoimmune connective tissue diseases. It occurs commonly in patients with Raynaud’s phenomenon

Hematologic/hypercoaguability

Any process that results in hyperviscosity may produce LR. Increased quantities of normal blood products, as occurs in polycythemia vera and thrombocytosis, as well as accumulation of abnormal proteins including cryoglobulins, cryofibrinogens, cold agglutinins, and paraproteins may cause intravascular sludging [1, 2]

Hypercoaguable states such as antiphospholipid syndrome (APS), Sneddon’s syndrome (SS), protein C and S deficiency, antithrombin III deficiency, factor V Leiden mutation, homocysteinemia, disseminated intravascular coagulation, thrombotic thrombocytopenia purpura, and deep vein thromboses are other examples. In particular, antiphospholipid syndrome, characterized by thrombosis and/or recurrent fetal loss with circulating antiphospholipids, is an important cause of LR to consider. LR may be the initial presenting symptom in 25–40 % of APS patients [3, 4]. It is even more frequent in patients with APS and underlying systemic lupus erythematosus (SLE) than in patients with APS alone and can signify an increased likelihood for neuropsychiatric SLE [5]. Sneddon’s syndrome, characterized by cerebrovascular events and LR and/or livedo racemosa, typically affects young to middle-aged women. The LR in Sneddon’s syndrome is widespread, almost always involving the trunk and buttocks, and often predates cerebrovascular events by years [6]

Vasculitis, autoimmune connective tissue diseases

Vasculitis, particularly of the small- or medium-sized arterioles, is associated with LR. Cutaneous polyarteritis nodosa is a classic example (Fig. 4.2). Other vasculitides to consider are Churg-Strauss syndrome, Wegener’s granulomatosis, microscopic polyangiitis, nodular vasculitis, rheumatoid vasculitis, and giant cell arteritis [7–9]. Autoimmune connective tissue diseases including SLE, rheumatoid arthritis, Sjörgen’s syndrome, dermatomyositis, and systemic sclerosis may present with large network pattern LR

Vessel obstruction

Embolic events or thromboses can obstruct the vessel lumen. Cholesterol emboli syndrome, seen in patients with atherosclerotic disease, results when a cholesterol plaque is dislodged from the vessel wall. It may be spontaneous or precipitated by catheter procedures and intraluminal operations. Usually, LR will present distal to the dislodged plaque [10]. Similarly, septic emboli, most commonly from Staphylococcus aureus, may produce LR [11]

Deposition disorders can also present with LR. Calciphylaxis, typically seen in the setting of end-stage renal disease, features calcium deposition within the vessel walls. Primary hyperoxalurias, rare autosomal recessive metabolic disorders associated with abnormal overproduction of serum oxalate and subsequent deposition in tissue, can manifest as LR. The deposition of these crystals results in intravascular obstruction, end-organ damage, and LR associated with ulceration and necrosis [12]

Livedoid vasculopathy is a combination of intraluminal obstruction and vessel wall pathology. The blood vessel lumina are filled with hyaline thrombi and fibrinoid material collects in the walls. It presents as distal lower extremity LR and recurrent painful purpuric ulcerations that heal with stellate, white atrophie blanche scars (Fig. 4.3) [13]

Medications

Thrombolytics, anticoagulants, and any drug that causes vasoconstriction can present with LR. One of the most well-known medications associated with LR is amantadine. Used in multiple sclerosis and Parkinson’s disease, amantadine can cause LR in up to 40 % of patients [14]. Other drugs that have been reported include minocycline, norepinephrine, heparin, and interferon [15]

Infections

Associated infections causing LR are often seen in the setting hypercoagulable states. Hepatitis C, causing mixed cryoglobulinemia, and mycoplasma pneumonia, causing cold hemagglutinin disease, are known causes. Other infections reported to be associated with LR include syphilis, streptococcemia, rheumatic fever, meningococcemia, rickettsial disease, endocarditis, and viral infections [16]

Neoplasms

Malignancies (renal cell carcinoma, breast cancer) resulting in vascular obstruction have been reported to cause LR in a few cases [17, 18]