PRIMULACEAE

(Primrose family)

1000 species in 20 genera are of cosmopolitan distribution especially found in north temperate regions.

[Summary yet to be added]

Anagallis

28 species are found in western Europe, Africa and Madagascar. One species is pantropical and two species are found in South America.

Anagallis arvensis L.

Scarlet Pimpernel, Red Pimpernel, Shepherd's Barometer, Poor Man's Weatherglass

The plant yields saponins and a proteolytic enzyme (Watt & Breyer-Brandwijk 1962). The plant has irritant properties (Pammel 1911, Muenscher 1951). The leaves can cause dermatitis in persons working in fields and forests (Behl et al. 1966). About 6% of individuals are sensitive and develop dermatitis when handling the flowers or leaves (Arnold 1968); he noted its relationship to Primula.

Cortusa

[syn. Corthusa]

Ten species are found on mountains from central Europe to Japan and Sakhalin.

Cortusa matthioli

The plant frequently produces irritant patch test reactions which probably result from a combination of mechanical injury and chemical irritation (Nestler 1912, Woods 1962).

Cyclamen L.

15 species are found in Europe and from the Mediterranean region to Persia.

Biberstein (1927) observed a positive patch test reaction to an unidentified Cyclamen in a 30 year old female who also reacted to Sedum spectabile Boreau (fam. Crassulaceae), to Myrtus communis L. (fam. Myrtaceae), and to an unidentified species of Tradescantia L. (fam. Commelinaceae). None of 7 control subjects reacted. Hjorth (1968) similarly reported that an unidentified Cyclamen produced a positive patch test reaction in one patient; none of nine other patients reacted (Hjorth 1968).

Cyclamen persicum

A positive patch test reaction to the leaf was observed in one patient (Agrup 1969).

Cyclamen persicum hybridum

A woman showed a positive patch test reaction to this hybrid and to Streptocarpus (Agrup and Fregert 1968).

Lysimachia

200 species are cosmopolitan, especially found in eastern Asia and North America.

Lysimachia vulgaris L.

Yellow Loosestrife

This plant dyes the hair yellow and kills flies and gnats in the house (Dioscorides 1st century, A.D.). According to Wren (1975), preparations of the plant have been used in folk medicine for their haemostatic activity.

Primula

500 species are found in the northern hemisphere especially in hilly districts. A few species are found elsewhere e.g. at the Strait of Magellan.

A few of the better known species are:

Primula auricula — Auricula

Primula eliator — Oxlip

Primula farinosa

Primula japonica

Primula sinensis — Chinese Primrose

Primula veris — Cowslip

[syn. Primula officinalis]

Primula vulgaris — Primrose

[syn. Primula acaulis] 

A great many hybrids occur.

Cultivation of Primula species in Great Britain:

The species of Primula most commonly grown as house-plants are P. obconica and P. malacoides. P. sinensis is retailed in smaller quantities while P. kewensis, P. floribunda, P. denticulata and P. mollis also appear in florists' shops from time to time. Other potentially allergenic species are unlikely to be contacted outside the larger botanical gardens (Rook & Wilson 1965).

The following species were found to have no irritating action (Nestler 1904):

Primula capitata

Primula clusiana

Primula farinosa

Primula floribunda

Primula hirsuta

Primula japonica

Primula megaraefolia

Primula minima

Primula officinalis

Primula rosea 

Primin in Primula species:

Sixteen of 82 species of the Primulaceae family which were investigated by the Craven screening test were found to contain primin, including:

Primula alpicola var. alba

Primula apennina

Primula denticulata

Primula eliator subsp. elatior

Primula hirsuta

Primula malacoides

Primula minima

Primula muscarioides

Primula praenitens

[syn. Primula sinensis]

Primula rosea

Primula veris subsp. veris

Primula vulgaris subsp. vulgaris 

In all the remaining species, other quinoid compounds were detectable.

The occurrence of primin is determined by origin, temperature, light, moisture, manuring, soil pH (content of lime), habitat and season, etc. The finding of primin in P. praenitens, P. eliator subsp. eliator, P. veris (syn. P. officinalis) appears to explain occasional reports of dermatitis, from these species e.g. cowslip (P. veris). The "Primula farinosa" reported by Sharpe (1912) to cause dermatitis appears to have been, in fact, P. mistassinica. This plant contains a yellow quinone.

Anagallis hirta, Dionysia aretiodes and Glaux maritima were found to contain primin (Hausen 1978).

These findings from a sensitive screening test were not in keeping with a supposition that primin was restricted to P. obconica, but further extraction studies were in progress.

Odour of Primula root:

The various species of Primula can be divided into four groups according to the odour of the root when injured. The odours resemble anise (Pimpinella), methyl salicylate and the disagreeable odour of bed bugs. A fourth group has no odour. Primula obconica belongs to the methyl salicylate group (Goris 1950, cited by Watt & Breyer-Brandwijk 1962).

Primin in Primula and other plants:

Hausen (1977) has detected primin or other quinoid compounds in species of Primula and in some other plants. Presumably the quantity present is rarely clinically significant, but further clinical investigation is required.

Primula cortusoides

This species has a mild skin-irritant effect (Nestler 1904, Maiden 1909b). The plant can produce irritant patch test reactions (Rook & Wilson 1965).

Primula farinosa

Cases of milkers' eczema were attributed to handling the udders of cows that had walked among the dew-laded flowers of this plant (Sharpe 1912). Since patch tests were not recorded, the association is suspect.

Primula malacoides

This species can produce irritant patch test reactions (Hjorth 1968). The plant has never been proved to cause allergic contact dermatitis (Rook & Wilson 1965).

Primula obconica

Origin of Primula obconica:

In 1880 Hance described Primula obconica as a new species collected around Ichang, province of Hupeh, China by T. Watters in 1879.

The petals (corollas) of P. obconica, contain primin. The "second allergen" of Cairns (1964) is a quinhydrone (Hausen 1978). For precise botany the original paper of Hausen (1978) should be consulted.

Primula obconica - Historical Aspects:

Primula obconica was introduced to Britain from China in 1880 and rapidly became established as a popular greenhouse plant throughout Europe and the United States. The first accounts incriminating this plant as a cause of dermatitis were published in horticultural journals (White 1888, White 1889, Anon 1889), and were received sceptically in England; one indignant gardener vigorously condemned "this vegetable viper". Shortly thereafter, reports began to appear in the medical journals first in England (Oldacres 1889) then in America (White 1890). Reports rapidly accumulated in England (Sym 1890, Clarke 1890, Lee 1890, Southern 1891, Swan 1891, Pooley 1893, Ackland 1893) and appeared in countries in Europe (Touton 1932). Ferguson (1890) suspected the hairs on the plant as the cause of the dermatitis. So numerous were the papers that it was predicted (Cooper 1899) that such a poisonous plant would be grown less and less frequently, but this prophecy has not been fulfilled. In 1906, Harrison called the plant the "the golden calf, or gold-laying hen, of dermatologists" and this primula remained the commonest cause of plant dermatitis in Great Britain into the 1960s (Rook 1961a).

In Germany anxiety about primula dermatitis was voiced in a question on the subject in the Reichstag; and in the United States cases were sufficiently numerous for a report by Foerster (1910) to be based on personal experience of 40 to 50 patients. These statistics are a measure of the plant's popularity, for most people are able to handle the leaves of the primula with impunity; and Shelmire (1939), who found an incidence of 8% among florists, was unable to discover a single case among 251 students tested against the leaves. Low (1924) was able to sensitise himself and his brother to P. obconica but failed to sensitise six other subjects.

Sensitisation by application of Primula obconica to the skin:

Kirk (1899) produced sensitisation by applying the plant repeatedly to irritated skin under occlusive dressings. Low (1935) sensitised himself and one of seven other subjects by rubbing the juice of the leaf into the abraded skin. Bloch and Steiner-Wourlisch (1926) rubbed a strong extract of the plant into the unbroken surface of the skin of twelve subjects and produced sensitisation in all of them. In a previous study by the same workers in which a weaker preparation was rubbed into the abraded skin, only 10 of the 24 subjects (41%) were sensitised.

Three non-sensitive individuals were sensitised by the continuous application of fresh Primula leaves to the forearm. The leaves were changed every 2 days. Sensitisation resulted in all three cases in 16, 17 and 29 days respectively. The skin of the face was found to react more strongly than the skin on other parts of the body. The author demonstrated a positive reaction of the oral mucous membrane to Primula on himself (Helmke 1937).

Maiden (1909b) also reported P. obconica as a cause of skin irritation.

Variety and cultivar allergenic specificity:

Hjorth (1966) found some differences in degree of allergenicity among eight named cultivars of this species. Pink forms of the plant give stronger patch test reactions than blue forms (Kirton 1974). In a male horticulturalist, only one single variety of primula out of 17 species tested was allergenic (Davies 1939).

Pollen of Primula obconica:

The damp pollen is allergenic and can cause dermatitis not only from contact but also by being in its vicinity without any direct contact (Rook 1961a).

Primula obconica - conditions of growth:

Weydahl (1906) found that primulas were more irritating to the skin if grown under hot and dry or under cool conditions; they were least irritating when grown under moist and warm conditions. This might explain why nurserymen who grow primulas in greenhouses seem to suffer fewer problems than those who grow these plants in homes or gardens (Anon 1906). It follows also that the severity of the reaction elicited by these plants in sensitised individuals is likely to vary accordingly.

Breeding of species of Primula obconica:

Because of the commercial importance of P. obconica, a wealth of new varieties has been cultivated by selection, hybridisation and some by mutation. As a result the plants at present available are entirely different from the original lilac variety imported from China (Maurer and Storck 1935).

The direct descendants of P. obconica are termed grandiflora. An attempt to obtain larger and longer lasting flowers by hybridisation between P. obconica and P. megaseafolia resulted in the popular P. obconica gigantea. P. megaseafolia is non-allergenic, but it appeared that the allergenic properties were inherited as a dominant trait so, unfortunately, P. obconica gigantea varieties tend to be more sensitising than the original grandiflora (Maurer and Storck 1935).

Arends, a German horticulturalist, was successful in breeding a primin-free Primula obconica cultivar but unfortunately a reduction in primin content also involved a lessening of the beauty of the flowers.

Relevance of primula dermatitis for hand eczema:

An ether extract of Primula obconica leaves produced 20 positive reactions (4 male, 16 female) in 431 persons (153 males, 278 females) investigated for hand eczema (Agrup 1969). In 4 of the 20 cases, allergy to Primula was considered the main cause or a contributory cause of the hand eczema (Agrup 1969).

Primula dermatitis in a blind person:

An eruption from Primula obconica affected the skin of the nose and around the eyes. The patient who was blind had been smelling the plant (Carman 1912).

Differential diagnosis of primula dermatitis:

Early writers noted a resemblance of primula dermatitis to seborrhoeic eczema and ringworm (Jamieson 1893), erysipelas (Pooley 1893) and urticaria (Southern 1891, Freeman 1897). Hjorth (1966) observed 453 individuals sensitive to Primula obconica during a six year period in Copenhagen. In some instances, the eruption resembled urticaria, erythema multiforme and scabies. He noted that the eruptions may not primarily or mainly affect the skin sites apparently in maximum contact with the plant. In eight cases primula dermatitis affected the eyelids only (Kaalund-Jørgensen 1951).

Primula obconica — Clinical features:

Rook & Wilson (1965) made a detailed study of a series of 25 patients — 24 females and one male.

The age at which sensitivity began ranged from 15 to 79, with an average of 51.6 years. The length of history before a diagnosis was made varied from 2 weeks to 10 years, with an average of 17.27 months. The sites principally involved (Table below) were the face, particularly round the mouth and on the eyelids, which were often red and swollen, the neck, arms and hands. Rarely, patches occurred on the ears, thighs, buttocks, or ankles. The affected areas itched, burned, and appeared red, often oedematous, and frequently blistered. A distinctive pattern was often seen, particularly on the arms and forearms, consisting of blotches and linear streaks. This appearance is very characteristic of plant dermatitis, and in Britain is nearly always due to contact with a primula.

Site Affected by Primula Dermatitis:

Sites Affected   Total    %

__________________________________

Eyelids       13    52

Cheeks and chin   16    64

Neck         14    56

Ears         1     4

Fingers       12    48

Hands         9    36

Arms         14    56

Ankles        1     4

Thighs and buttocks  2     8

Tongue        1     4

On the sides of the fingers quite large blisters sometimes formed after the patient had pulled dead leaves off the plant. Mucosal lesions were rare, but one patient complained of soreness of the lips and tongue, while another suffered not only from an extensive rash but from pyrexia, coryza, and conjunctivitis as a result of contact with a plant.

Less easy to recognize was the occasional mild case in which the only sign of primula sensitivity consisted in a single transient itching red patch, usually on the chin or the side of the neck, or recurrent irritation, redness, and swelling of the eyelids.

In severe cases, which may occur when the diagnosis is overlooked and the patient continues to handle the plants, the eruption may become very extensive and the face grossly oedematous, and fever and constitutional symptoms may develop. In one of the patients, not included in the present series, an attack of erythema multiforme complicated the already widespread dermatitis.

Hjorth (1970) reported that the degree of sensitivity and the intensity of exposure determine the pattern of dermatitis.

Removal of dead flowers by a housewife with a low degree of sensitivity may produce a vesicular eruption on the sides of the fingers, indistinguishable from a dyshidrotic eczema. The textbook picture of plant dermatitis with vesicles in linear patterns or violent erythema and oedema occurs in half of the cases only (Bonnevie 1939).

The resinous excretion adheres to the fingers and a highly sensitive patient's activity and agility determines further dissemination. If a patient dresses after nursing her flowerpots, indistinct streaking fingermarks develop on the shoulders and the thorax. Allergen sticking to the fingertips may cause eruptions mainly localized to the ano-genital region, the ears or the nostrils (Bonnevie 1939, Hjorth 1966). Sometimes the initial diagnoses have been neurodermatitis of the neck or acute seborrheic eczema of the scalp. Erythema multiforme and id-like papular universal eruptions mistaken for scabies are uncommon but have been observed by several authors (Bonnevie 1939, Rook & Wilson 1965, Hjorth 1966). The latter types of eruption suggest a haematogenous dissemination or possibly a reaction to allergen inhaled with the dust.

If patch tests with primula are performed only in clinically suspected cases, the patterns of dermatitis observed must of necessity comply with the textbook of descriptions of plant dermatitis. Where standard patch tests serve as a clue to diagnosis, the atypical patterns will be observed. In such cases the origin of the dermatitis is only revealed by detailed interrogations prompted by the positive patch tests (Bonnevie 1939, Hjorth 1966).

Conjunctivitis, keratitis and iritis have been reported in association with primula dermatitis (Grant 1962).

Primula spp. in Japan:

In Japan, dermatitis from Primula is very rare except in occupational cultivators. In a greenhouse worker who developed dermatitis of the hands and face, patch tests to the leaves and flowers (including calyces), diluted ten times, produced positive reactions with P. obconica, P. malacoides and P. sinensis (Harada and Masuda 1972).

A woman gardener who carried out the pollination of P. obconica developed dermatitis of the face and back of hand. Patch tests to stamens, calyces, leaf backs and stems produced positive reactions (Endo, M. and Honda, M. 1972, in discussion of Harada and Masuda 1972).

Primula spp. in Europe:

Dermatitis from Primula obconica has become less common in Denmark and possibly in Europe generally as awareness of the allergenicity of the plant has spread and horticulture of the plant has diminished. However, the plant is becoming more commonly sold in California thus reversing the historical trend of interest in this plant.

Chemical prevention of primula dermatitis:

Helmke (1938) found that washing the area of skin exposed to a primrose leaf with a 25 per cent solution of ammonia prevented a dermatitis if it was done within 15 minutes. After longer periods or in weaker solutions the preventive property was much less marked. If a primrose leaf is soaked in a 25 percent solution of ammonia for 24 hours the dermatitis producing property is entirely lost.

Primula poculiformis

Prosser White (1934) wrote that he "knows of a lady in whom the Primula obconica or poculiformis primrose sets up its characteristic trouble, whereas to her gardener it is quite innocuous."

Primula sieboldii

This species has skin-irritant properties (Nestler 1904).

Primula sinensis

Dermatitis from the plant was reported by Gillett (1896). This species has skin irritant properties (Nestler 1904, Maiden 1909b). The plant can produce irritant patch test reactions (Hjorth 1968). Only 1.4% of 277 persons who were patch tested to the leaf showed positive reactions (Fregert and Hjorth 1969). These authors concluded that the plant is a potential irritant by patch test. P. sinensis has been shown to cause allergic contact dermatitis at the most very rarely (Rook & Wilson 1965).

Primula suaveolens

Sensitisation to this species which is said to be indigenous to Oviedo, Spain, was reported by De Argumosa (1951).

Primula veris

Cowslip

This plant is a common wild flower in the woods of all parts of Great Britain. Hjorth (1968) recorded two positive patch test reactions to the plant. Allergenicity is not proven.

Primula vulgaris

Primrose

The plant and root were used in herbal medicine: "Of the leaves of Primroses is made as fine a salve to heal wounds as any that I know. Do not see your poor neighbour to go with wounded limbs when an halfpenny cost will heal them" (Culpeper 1653).

References

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