History of peanut cultivation

Peanut ( Arachis hypogea ) is a native South American legume that has been valued for many centuries. Peanut kernels have been found in Peruvian archaeological sites demonstrating organized agriculture 10,000 years ago. In contrast, the absence of peanuts from Greek and Roman remains and writings and pre-Columbian Old World records, strongly suggests that peanut was unknown to these early European civilizations. By the time the Conquistadores arrived in South America, the Incas felt that peanuts were “a luxury of the rich and curious (rather than) a food for the poor.” This high status of peanut in the South American diet contrasts with reports of customs on Hispaniola, Columbus’s landfall in the New World. Fernandez (1535) noted “It [peanut] is a healthy food but it is not eaten by Christians unless they are unmarried males or children or slaves or common people. Its consumption among the Indians is very common.”

Peanut cultivation spread with the conquest of Central and North America and was introduced to Africa as a food for slaves. Today it is a significant cash crop particularly in West Africa. Up to the nineteenth century, peanut was used in North America as a food for slaves, poor whites, and increasingly as food for animals. In our time, the largest producers of peanuts (India and China) grow peanuts largely for animal rather than human consumption. The growth of peanut as a cash crop occurred in North America on the back of 2 developments: the American Civil War and mechanization of vegetable oil production. Peanuts were grown extensively in the southern United States before the Civil War. Its use as an easily transportable high-energy food increased during the Civil War and spread to northern cities. It is difficult to say when peanut and peanut butter appeared in significant amounts in Europe. However, by the 1970s, peanut had become a common food in the United Kingdom, in both its nut and butter forms. The United States produces 8 billion kg per annum.

Botany and biology of peanut and peanut proteins

Peanut is the fruit of the legume Arachis hypogea . It is also know as the goober nut or earth nut, and more commonly as a groundnut. The German for peanut is erdnusse (groundnut). It is called a groundnut because the seed pod initially appears on the branches of the plant and as it increases in weight the branch bends and the dependent pods become buried in the soil where they mature before harvesting. Peanut is a high protein food, 24% by weight and is therefore comparable with cheese, fish, and beef. Most of peanut’s 49% fat content is unsaturated making it an attractive and stable source of oil for human consumption. Fiber levels are comparable with wholemeal bread (1.5 g/100 g).

Peanuts contain ∼25% protein. The major peanut proteins to which most North American and northern European individuals develop an allergic reaction are Ara h1, Ara h 2 and Ara h3, respectively but in southern Europe Ara h 8 and Ara h 9 are more dominant ( Table 1 for summary). The allergens in peanut have been studied intensively for more than 20 years, seeking to find a biochemical basis for the severity of peanut allergy and to explore whether protein modifications result in reduced allergenicity. Although neither aspiration has been fully satisfied much has been learned.

Efforts have been made to reduce the allergenicity of major peanut allergens, particularly Ara h 2, with in vitro studies showing significant reductions in IgE binding and in basophil histamine release. However, modification of peanut proteins may alter its botanic function and it does not address the broad diversity of allergenic proteins that exist in peanut plants, where elimination of one will probably not eliminate the allergenic potential of other proteins.

Botany and biology of peanut and peanut proteins

Peanut is the fruit of the legume Arachis hypogea . It is also know as the goober nut or earth nut, and more commonly as a groundnut. The German for peanut is erdnusse (groundnut). It is called a groundnut because the seed pod initially appears on the branches of the plant and as it increases in weight the branch bends and the dependent pods become buried in the soil where they mature before harvesting. Peanut is a high protein food, 24% by weight and is therefore comparable with cheese, fish, and beef. Most of peanut’s 49% fat content is unsaturated making it an attractive and stable source of oil for human consumption. Fiber levels are comparable with wholemeal bread (1.5 g/100 g).

Peanuts contain ∼25% protein. The major peanut proteins to which most North American and northern European individuals develop an allergic reaction are Ara h1, Ara h 2 and Ara h3, respectively but in southern Europe Ara h 8 and Ara h 9 are more dominant ( Table 1 for summary). The allergens in peanut have been studied intensively for more than 20 years, seeking to find a biochemical basis for the severity of peanut allergy and to explore whether protein modifications result in reduced allergenicity. Although neither aspiration has been fully satisfied much has been learned.

Efforts have been made to reduce the allergenicity of major peanut allergens, particularly Ara h 2, with in vitro studies showing significant reductions in IgE binding and in basophil histamine release. However, modification of peanut proteins may alter its botanic function and it does not address the broad diversity of allergenic proteins that exist in peanut plants, where elimination of one will probably not eliminate the allergenic potential of other proteins.

Epidemiology

Peanut allergy seems to develop early in life with most affected children in the United States and the United Kingdom developing symptoms before the age of 2 years. The age of exposure and age of first reaction to peanut have both decreased in recent years in the United States.

Family studies have shown that peanut allergy is more common in first-degree relatives of children with peanut allergy than in the general population. It remains uncertain if this can solely be explained by a shared genetic background or also reflects environmental factors that are shared in families.

The known international variation in peanut allergen recognition probably reflects alternative cooking and intercultural feeding practices that may increase or decrease peanut’s in vitro allergenicity ( Fig. 1 ). In addition, timing of its first introduction into the diet affects prevalence as clearly demonstrated when comparing peanut prevalence between genetically similar but geographically separate Jewish populations (Israel vs United Kingdom) with different feeding practices.

Different cooking methods alter peanut’s in vitro allergenicity in different ways. Boiling reduces IgE binding, roasting increases it. This woman in Keneba, Gambia, is dry roasting peanut kernels.

(C ourtesy of Dr Kerry Jones, Medical Research Council Laboratories, Keneba; with permission.)

Serologic studies have shown that the diversity of IgE recognition of peanut proteins is more associated with clinical outcome than recognition of individual proteins although recognition of Ara h 2 is repeatedly shown to be associated with more severe (mostly respiratory) symptoms. It has also been shown that Ara h 2 sensitivity is more likely to be associated with reactivity in formal challenge than recognition of Ara h 8, which probably reflects Bet v1-related cross-reactivity. At the present time, the most useful predictors of persistence after the first 2 years of life are a maximum wheal size of >6 mm for the peanut skin prick test (SPT) or a peanut-specific IgE >3 kilounits of antibody (kUA)/L.

Cellular-based assays of T-cell recognition of peanut peptides, and of IgE and IgG, G ₁ and IgG ₄ diversity, tend to show that there is a diverse spectrum of reactivity with no particular pattern of antibody production that could easily predict severity in a way that is clinical useful. Combination scores that account for both dose and clinical reaction during food challenge have been associated with specific IgE levels but there remains the problem that reactivity in a formal food challenge is not strongly linked with reported reaction severity in community reactions (reactions in the field).

Peanut allergy is a marker for other atopic disorders

Individuals with peanut allergy are almost universally atopic in other ways, with rates of asthma, atopic dermatitis (AD), and rhinitis that are higher than the general population. In the United Kingdom, monoallergy to peanut is a rare finding, with less than 5% of cases showing no other sensitization. This can be a good clue to the diagnosis when meeting a new referral for evaluation. In addition, it has been known for 2 decades that asthma, particularly poorly controlled asthma, is associated with fatal outcome in food allergy, particularly peanut allergy, and conversely that an existing diagnosis of peanut allergy is associated with worse respiratory outcomes in asthmatic children. Furthermore, children with peanut allergy who are clinically considered to have outgrown preexisting asthma continue to show increased levels of exhaled nitric oxide (eNO), implying persisting inflammation in the airway. In view of these data, it is considered best practice to ensure optimal asthma control as a key part of managing peanut allergy (see later discussion). Similarly AD is a common clinical finding in children with peanut allergy. AD is considered the earliest marker of atopic predisposition.

Much higher odds of developing peanut allergy has been found if a mother (retrospectively recalled at 5–7 years) had applied skin creams containing peanut oil to infant skin. Experimental work showed application of peanut to both intact and especially to abraded mouse skin caused migration of Langerhans cells out of the skin and to systemic sensitization, as measurable by increased serum peanut-specific IgE, and a T _h 2 biased cytokine profile.

An interesting observational study from the United Kingdom has suggested that compared with control families (no food allergy) and families with a child at high risk for but not actually demonstrating peanut allergy (the index child had egg allergy), families with a child with peanut allergy were more likely to consume peanut and especially peanut butter in the home, with a dose-response relationship evident between nonoral exposure to peanut and having peanut allergy.

Prevalence of peanut sensitization and confirmed allergy

At present, there are estimates that up to 9% and 11% of North American and British children of 8 years or older and 8.9% of Australian infants of 12 months of age (K. Allen, personal communication, 2010) are sensitized to peanut although less than half of these children can be proved to be allergic to peanut by food challenge (see later discussion). In contrast the Early Prevention of Asthma and Allergy in Childhood (EPAAC) study found that in infants aged 1 to 2 years with moderate AD, sensitization to peanut could be found in more than 20% of children. It is unclear whether this is primary sensitization or cross-reactive sensitization with birch pollen and other plant allergens that may have been encountered by the inhaled route before oral exposure to peanut.

Several studies suggest a steady increase in the prevalence of peanut allergy from the mid-1990s. For example, at 3 to 4 years of age, the Isle of Wight cohort born in 1989 had a 1.3% peanut sensitization prevalence and a 0.6% prevalence of actual clinical peanut allergy. No formal diagnostic challenges were performed. Subsequent birth cohort studies from the Isle of Wight and a cross-sectional 2-center study from the UK mainland showed the rate of peanut allergy (proved by challenge) had increased to 1.8% by 2005.

Population-based studies that result in a gold standard diagnostic double-blind, placebo-controlled, food challenge are less common in the United States but self-reported surveys conducted by telephone in the United States have shown similar figures and a similar increase from 0.4% in 1997 to 1.4% in 2008. The 2005/2006 National Health and Nutrition Examination Survey study reported an estimate prevalence of peanut allergy of 1.3%.

Patterns of clinical reactivity

The diagnosis of peanut allergy is simple to make in the presence of known exposure to peanuts and a stereotypical reaction ( Table 2 ). Reactions typically start soon after exposure and it is usually possible to identify peanut in the food eaten Most reactions to peanut are benign and are survived. However, peanut is overwhelmingly and disproportionately represented in case series of severe and fatal outcomes, particularly in community-based retrospective surveys of deaths and severe allergic reactions. Methodologically there may be biased reporting of reactions when peanut is implicated compared with more unusual foods that are not recognized by emergency staff as allergens or foods that are considered more mundane such as milk and egg.

Diagnosis of peanut allergy

As shown in Table 2 the features of a peanut allergic reaction are simple to distinguish as reactions are typical and are usually similar in individuals who have repeat reactions and in formal challenge settings. Observed variation in reactions with time may be caused by the onset of asthma, dose variation, or extrinsic factors such as exercise, infection, and other cofactors.

Although the double-blind, placebo-controlled food challenge is considered the gold standard for diagnosis, it is logistically demanding and time consuming. Therefore, an open food challenge is acceptable in most settings, especially for young children. Most peanut challenges are well tolerated; most children (>90%) who react to the challenge do not need epinephrine, even with conservative criteria for intervention. Families respond favorably to food challenges, even when they result in a reaction. Although a formal food challenge is not possible in all diagnostic settings, more than half of the individuals who undergo a food challenge do not react, even if their SPT or serum IgE level suggests the presence of a peanut allergy.

Several investigators have developed specific values for SPT (>6–8 mm in most reports) or peanut-specific serum IgE levels (>14–15 kUA/L) that would indicate a likely positive reaction during an oral food challenge. Although these may be useful in deciding if a diagnostic challenge is necessary or can be postponed, they do not add greatly to the scenario of a carefully taken history that characterizes a reaction as likely to have been caused by peanut, with a positive SPT or specific IgE level that might be less than the decision point. In clinical practice, a typical history (see Table 2 ) and supportive tests mean a true diagnosis of peanut allergy is likely to be present in 85% of cases. Therefore it is not immediately and automatically necessary to challenge every child who presents with a history of reactivity to peanut. Research protocols may demand challenges but routine clinical practice is now more commonly using challenges to determine if peanut allergy has resolved. It is now possible to use more subtle assessments that combine the effects of known predictors of challenge outcome with others whose effect has been difficult to quantify, such as age and sex.