Loxoscelism (/lɒkˈsɒsɪlɪzəm/) is a condition occasionally produced by the bite of the recluse spiders (genus Loxosceles). The area becomes dusky and a shallow open sore forms as the skin around the bite dies (necrosis). By 2006, it was the only proven type of necrotic arachnidism in humans. While there is no known therapy effective for loxoscelism, there has been research on antibiotics, surgical timing, hyperbaric oxygen, potential antivenoms and vaccines. Because of the number of diseases that may mimic loxoscelism, it is frequently misdiagnosed by physicians.

Loxoscelism was first described in the United States in 1879 in Tennessee. Although there are up to 13 different Loxosceles species in North America (11 native and two non-native), Loxosceles reclusa, also known as the Brown Recluse, Fiddleback, or Violin spider, is the species most often involved in serious envenomation. L. reclusa has a limited habitat that includes the Southeast United States. In South America, L. laeta, L. intermedia (found in Brazil and Argentina), and L. gaucho (Brazil) are the three species most often reported to cause necrotic bites.

Loxoscelism may present with local and whole-body symptoms:

Loxosceles venom has several toxins; the most important for necrotic arachnidism is the enzyme sphingomyelinase D. It is present in all recluse species to varying degrees and not all are equivalent. This toxin is present in only one other known spider genus (Sicarius). The toxin dissolves the structural components of the cell membrane generating cyclic phosphates that perhaps act as a trigger for cellular self-destruction. The area of destruction is limited to the presence of the enzyme which cannot reproduce.^{[citation needed]}

The spider biting apparatus is short and bites are only possible in experimental animals with pressure on the spider's back. Thus many bites occur when a spider is trapped in a shirt or pant sleeve. There is no commercial chemical test to determine if the venom is from a brown recluse. The bite itself is not usually painful. Many necrotic lesions are erroneously attributed to the bite of the brown recluse. Skin wounds are common and infections will lead to necrotic wounds, thus many severe skin infections are attributed falsely to the brown recluse. Many suspected bites occurred in areas outside of its natural habitat. A wound found one week later may be misattributed to the spider. The diagnosis is further complicated by the fact that no attempt is made to positively identify the suspected spider. Because of this, other, non-necrotic species are often misidentified as a brown recluse. Several certified arachnologists are able to positively identify a brown recluse specimen on request.

Reports of presumptive brown recluse spider bites reinforce improbable diagnoses in regions of North America where the spider is not endemic such as Florida, Pennsylvania, and California.

The mnemonic "NOT RECLUSE" has been suggested as a tool to help professionals more objectively exclude skin lesions that were suspected to be loxosceles. Numerous (should be solitary), Occurrence (wrong geography), Timing (wrong season), Red Center (center should be black), Elevated (should be shallow depression), Chronic, Large (more than 10 cm), Ulcerates too quickly (less than a week), Swollen, Exudative (there should be no pus, it should be dry)

Systemic loxocelism, a rare but severe illness caused by a brown recluse bite, can be diagnosed through urinalysis. However, a blood test for elevated lactate dehydrogenase and total bilirubin have been shown to be a more sensitive test.