Livedo reticularis

Livedo reticularis is a common skin finding consisting of a mottled reticulated vascular pattern that appears as a lace-like purplish discoloration of the skin.[1] The discoloration is caused by reduction in blood flow through the arterioles that supply the cutaneous capillaries, resulting in deoxygenated blood showing as blue discoloration. This can be a secondary effect of a condition that increases a person's risk of forming blood clots, including a wide array of pathological and nonpathological conditions. Examples include hyperlipidemia, microvascular hematological or anemia states, nutritional deficiencies, hyper- and autoimmune diseases, and drugs/toxins.

Livedo reticularis
Livedo reticularis secondary to obscure severe infrarenal aortoiliac stenosis with severe transient lactic acidosis.
Specialty	Dermatology, cardiology
Symptoms	Purpura, mottling of the skin, blood clots, skin discoloration
Causes	Autoimmune diseases, hyperlipidemia, poisons, drug abuse

The condition may be normal or related to more severe underlying pathology.[2] Its differential diagnosis is broadly divided into possible blood diseases, autoimmune (rheumatologic) diseases, cardiovascular diseases, cancers, and endocrine disorders. It can usually (in 80% of cases) be diagnosed by biopsy.[3]

It may be aggravated by exposure to cold, and occurs most often in the lower extremities.

The condition's name derives from the Latin livere which means bluish, and reticular which refers to the net-like pattern.[4]

Causes

A number of conditions may cause the appearance of livedo reticularis:

• Cutis marmorata telangiectatica congenita, a rare congenital condition
• Sneddon syndrome – association of livedoid vasculitis and systemic vascular disorders, such as strokes, due to underlying genetic cause[5]
• Idiopathic livedo reticularis – the most common form of livedo reticularis, completely benign condition of unknown cause affecting mostly young women during the winter:[6] It is a lacy purple appearance of skin in extremities due to sluggish venous blood flow. It may be mild, but ulceration may occur later in the summer.[7]
• Secondary livedo reticularis:
  • Vasculitis autoimmune conditions:
    • Livedoid vasculitis – with painful ulceration occurring in the lower legs
    • Polyarteritis nodosa
    • Systemic lupus erythematosus[8]
    • Dermatomyositis
    • Rheumatoid arthritis
    • Lymphoma
    • Pancreatitis[9]
    • Chronic pancreatitis[10]
    • Tuberculosis
  • Drug-related:
    • Adderall (side effect)
    • Amantadine (side effect)
    • Bromocriptine (side effect)
    • Beta interferon treatment, e.g. in multiple sclerosis[11][12][13]
    • Livedo reticularis associated with rasagiline[14]
    • Methylphenidate and dextroamphetamine-induced peripheral vasculopathy[15]
    • Gefitinib[16]
  • Obstruction of capillaries:
    • Cryoglobulinaemia – proteins in the blood that clump together in cold conditions[17]
    • Antiphospholipid syndrome due to small blood clots
    • Hypercalcaemia (raised blood calcium levels which may be deposited in the capillaries)
    • Haematological disorders of polycythaemia rubra vera or thrombocytosis (excessive red cells or platelets)
    • Infections (infective endocarditis, syphilis, tuberculosis, Lyme disease)
    • Associated with acute kidney injury due to cholesterol emboli status after cardiac catheterization
    • Arteriosclerosis (cholesterol emboli)[18][19] and homocystinuria (due to Chromosome 21 autosomal recessive Cystathionine beta synthase deficiency)
    • Intra-arterial injection (especially in drug addicts)
  • Ehlers-Danlos syndrome – connective tissue disorder, often with many secondary conditions, may be present in all types
  • Pheochromocytoma[20]
  • Livedoid vasculopathy and its association with factor V Leiden mutation[21]
  • FILS syndrome (polymerase ε1 mutation in a human syndrome with facial dysmorphism, immunodeficiency, livedo, and short stature)[22]
  • Primary hyperoxaluria, oxalosis (oxalate vasculopathy)[23][24][25][26][27]
  • Cytomegalovirus infection (very rare clinical form, presenting with persistent fever and livedo reticularis on the extremities and cutaneous necrotizing vasculitis of the toes)[28]
  • Generalized livedo reticularis induced by silicone implants for soft tissue augmentation[29]
  • As a rare skin finding in children with Down syndrome[30][31]
  • Idiopathic livedo reticularis with polyclonal IgM hypergammopathy[32]
  • CO₂ angiography (rare, reported case)[33]
  • A less common skin lesion of Churg-Strauss syndrome[34]
  • Erythema nodosum-like cutaneous lesions of sarcoidosis showing livedoid changes in a patient with sarcoidosis and Sjögren's syndrome[35]
  • Livedo vasculopathy associated with IgM antiphosphatidylserine-prothrombin complex antibody[36]
  • Livedo vasculopathy associated with plasminogen activator inhibitor-1 promoter homozygosity and prothrombin G20210A heterozygosity[36]
  • As a first sign of metastatic breast carcinoma (very rare)[37]
  • Livedo reticularis associated with renal cell carcinoma (rare)[38]
  • Buerger's disease (as an initial symptom)[39]
  • As a rare manifestation of Graves hyperthyroidism[40]
  • Associated with pernicious anaemia[41]
  • Moyamoya disease (a rare, chronic cerebrovascular occlusive disease of unknown cause, characterized by progressive stenosis of the arteries of the circle of Willis leading to an abnormal capillary network and resultant ischemic strokes or cerebral hemorrhages)[42]
  • Associated with the use of a midline catheter[43]
  • Familial primary cryofibrinogenemia.[44]

Diagnosis

Livedo reticularis is diagnosed by its clinical appearance and history. No further test or examination confirms idiopathic livedo reticularis, however, further investigations may be undertaken where an underlying cause is suspected such as skin biopsies, or blood tests for antibodies associated with antiphospholipid syndrome or systemic lupus erythematosus.[45]

Treatment

Other than identifying and treating any underlying conditions in secondary livedo,[46] idiopathic livedo reticularis may improve with warming the area. A further treatment option for livedo reticularis of the lower limbs is chemical lumbar sympathectomy.[47] Scientists at Peking University have developed a protocol to minimise complications traditionally linked to this procedure. Known as "selective chemical lumbar sympathectomy" it involves injecting an inactivating agent behind the anterior fascia, which only targets gray rami communicantes, to help achieve therapeutic efficacy in vasodilation.[48]

See also

• Livedoid dermatitis
• Perinatal gangrene of the buttock
• erythema ab igne (AKA livedo recticularis e calore) - a rash caused by prolonged heat exposure (e.g. hot water bottle or heat pad)

References

1. Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 1615. ISBN 978-1-4160-2999-1.
2. "livedo reticularis" at Dorland's Medical Dictionary
3. Kroshinsky; Stone, John H.; Bloch, Donald B.; Sepehr, Alireza (February 2009). "Case 5-2009 — A 47-Year-Old Woman with a Rash and Numbness and Pain in the Legs". New England Journal of Medicine. 360 (7): 711–20. doi:10.1056/NEJMcpc0807822. PMID 19213685.
4. Sundriyal, Deepak; Kumar, Naveen; Kumar, Gaurav; Walia, Meenu (15 May 2014). "Livedo reticularis heralding hypercalcaemia of malignancy". Case Reports. 2014: bcr2013201371. doi:10.1136/bcr-2013-201371. PMC 4024535. PMID 24832704.
5. Sneddon IB (April 1965). "Cerebro-Vascular Lesions And Livedo Reticularis". British Journal of Dermatology. 77 (4): 180–5. doi:10.1111/j.1365-2133.1965.tb14628.x. PMID 14278790.
6. Gibbs, Mark B.; English, Joseph C.; Zirwas, Matthew J. (2005). "Livedo reticularis: an update". J Am Acad Dermatol. 52 (6): 1009–19. doi:10.1016/j.jaad.2004.11.051. PMID 15928620.
7. Feldaker M, Hines E, Kierland R (1955). "Livedo reticularis with summer ulcerations". AMA Arch Derm. 72 (1): 31–42. doi:10.1001/archderm.1955.03730310033007. PMID 14387292.
8. Golden R (March 1963). "Livedo reticularis in systemic lupus erythematosus". Arch Dermatol. 87 (3): 299–301. doi:10.1001/archderm.1963.01590150015002. PMID 13948706.
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External links

Classification	D ICD-10: R23.1 ICD-9-CM: 782.61 MeSH: D054068 DiseasesDB: 7546
External resources	MedlinePlus: 001478

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