Systemic quinine photosensitivity with photoepicutaneous cross-reactivity to quinidine

A 75-year-old man developed an eczematous eruption on the face and dorsal aspects of the hands one July after 3 weeks' treatment with quinine, 0.25 g nightly, for nocturnal leg cramps. The photoreaction cleared within a week of quinine being stopped. UVA and UVB erythema threshold determinations, after the acute episode had subsided, were normal. A photopatch test was positive for irradiated quinine down to a concentration of 0.01% and for unirradiated quinine to 0.5%. The test with the isomer quinidine was positive only when irradiated, down to a concentration of 0.01%. Preirradiated samples of quinine and quinidine were negative. Whereas in contact allergy quinine and quinidine usually do not cross-react, after systemic photosensitization, the 2 isomers probably form a common photoproduct, accounting for the cross-reactivity.     

Quinine and quinidine cross-react after systemic photosensitization in the mouse

Using a protocol for induction of photoallergy in the mouse after systemic administration, quinine was shown to be just as potent a photosensitizer as its d-isomer, quinidine. The dose-response curves for the two isomers followed a similar course both for induction and elicitation. Cross-reaction experiments, where induction and challenge were performed with different isomers, indicated that quinine and quinidine cross-react. Traces of the isomer as a contaminant in the test compound are not likely to account for this cross-reactivity. For practical purposes, photosensitization to one of these two quinoline methanol isomers seems to exclude the future use of the other.     

Cutaneous hyperpigmentation due to chronic quinine ingestion

Striking hyperpigmentation developed on the arms of a 66-year-old man following protracted oral ingestion of quinine. Although this phenomenon is well described in conjunction with other similar drugs, including quinidine, it has not been well documented following exposure to quinine. This adverse event is cosmetic in nature and is not associated with functional impairment.     

Photosensitivity induced by quinidine sulfate: experimental reproduction of skin lesions.

A case of quinidine sulfate-induced photodermatitis is reported. The photosensitive reaction to quinidine sulfate was reproducible in the photopatch test and after oral intake plus ultraviolet A (UVA) irradiation. Eczematous dermatitis was provoked after intradermal injection of in vitro UVA-irradiated quinidine sulfate only in the presence of patient's serum. The clinical picture and histology suggest an allergic reaction. The photobinding of quinidine sulfate to a potential carrier protein in skin or serum seems to be of crucial importance for this type of photodermatitis. Quinidine sulfate is frequently used as an antiarrhythmic drug. Its potential as a photosensitizer should always be considered.     

Quinidine-induced photoallergy. A clinical and experimental study

Photoallergies are type-IV allergic reactions of a special kind. Photoallergies due to quinidine sulphate were described as early as 1942. We present a case of quinidine sulphate-induced photodermatitis. The photoallergic reaction to quinidine sulphate was reproducible not only after oral intake but also in the photopatch test. In addition, an eczematous dermatitis was provoked after intradermal injection of quinidine sulphate previously exposed to UV-A irradiation in vitro together with serum taken from the patient. No dermatitis was seen with quinidine sulphate irradiated in the absence of serum. The binding of the hapten quinidine sulphate to a potential carrier protein in the serum seems to be of crucial importance in this type of photodermatitis. Quinidine sulphate is frequently used as an antiarrhythmic drug. Its potential photoallergenic action should always be considered.     

Quinidine photosensitivity.

Photodermatitis occurring in three patients taking oral quinidine sulfate cleared when the drug was discontinued and recurred when it was readministered. The dermatitis was experimentally reproduced with long-wave ultraviolet light (UV-A, 320-400 nm) in these three patients, who also exhibited a decreased minimal erythema dose (MED) to hot quartz irradiation. Patients taking quinidine who had no dermatitis exhibited normal MEDs and normal response to UV-A. Normal subjects injected intradermally with quinidine and irradiated with UV-A showed no reaction. These observations indicate that the photosensitive dermatitis to quinidine that occurred in the three patients is idiosyncratic and that the UV-A is at least partially responsible for the development of the dermatitis that correlates with the absorption of quinidine in the UV-A range. Quinidine must be considered among the drugs that can produce photosensitive dermatitis.     

Ultraviolet B irradiation inhibits the induction of photoallergy to systemically administered quinidine in the mouse.

In albino mice photosensitized to quinidine, 100 mg/kg by intraperitoneal injection, pretreatment of the induction area with ultraviolet B (UVB) on 3 consecutive days was shown to significantly reduce the inflammatory response when the mice were challenged at a distant site 1 week later. Mice controlled for phototoxicity did not react. The inhibition was dose-dependent within the UVB dose range tested (0.05-1.0 J/cm2 x 3), being almost complete with the highest doses. Inhibition, although somewhat less pronounced, was also seen when an area on the back, distant from the induction site, was preirradiated following a similar protocol. The reduced response at elicitation persisted when the time to challenge was increased up to 4 weeks. At 5 weeks, a second attempt to photosensitize the previously inhibited animals failed, suggesting that a state of tolerance had been acquired. The timing of the UV exposure in relation to the photoactive chemical is critically important in determining whether an exposure promotes or inhibits photoallergic sensitization.     

Systemic quinine photosensitivity

A 72-year-old woman developed a photodistributed skin eruption while taking quinine hydrochloride (250 mg) once or twice weekly for recumbency cramps. The histopathology showed an eczematous reaction. Phototesting after quinine therapy had been discontinued for one month revealed normal erythema thresholds for ultraviolet (UV) light in the A range (17 J/cm2) and UV light in the B range (20 mJ/cm2). A second phototest after a ten-day period of reexposure to quinine hydrochloride (250 mg daily) showed a drastically lowered threshold for UV light in the A range (less than 1.0 J/cm2), while the test for UV light in the B range was unchanged. The patient's dermatitis also exacerbated with pronounced itching. The histopathologic results from a positive test site were similar to those of her eczematous lesions. We believe this to be the first documented case of systemic quinine photosensitivity. The clinical picture, the results of the phototests, and the histopathology suggest a photoallergic mechanism.     

Quinidine photosensitivity

A 55-year-old woman developed a dermatitis confined to light-exposed areas while taking quinidine gluconate, warfarin sodium, furosemide, spironolactone, and digoxin after cardiac surgery. Phototesting indicated a normal erythematous response to 290- to 320-nm ultraviolet radiation, but she developed erythema from 6 joules/sq cm of 320- to 400-nm radiation (ultraviolet A [UV-A]), a much lower dose than needed to produce a reaction in normal individuals. Two days after she discontinued quinidine and warfarin, phototesting showed no reaction to as much as 20 joules/sq cm of UV-A. One week after resuming quinidine (but not warfarin), she again reacted to 8 joules/sq cm of UV-A. No reactivity was elicited when the preparation was applied to the skin or injected into the dermis either with or without subsequent UV-A irradiation.     

The action spectrum in quinine photosensitivity

The action spectrum for 24-h ultraviolet erythema was determined in three elderly patients who presented with a photosensitive eruption and who were taking quinine sulphate for night cramps. In each case the in vivo action spectrum was consistent with the absorption spectrum of quinine, and extended from about 370 nm to at least the lower wavelength limit of terrestrial sunlight (approximately 300 nm). Calculations based upon the combination of the action spectrum for quinine photosensitivity, the spectrum of terrestrial sunlight, and the transmission properties of various topical sunscreens, indicated that a broad absorption spectrum sunscreen would be required to provide adequate photoprotection.     

Photoallergy to systemic quinidine in the mouse

Using the mouse, photoallergy to the antiarrhythmic agent quinidine could be induced following systemic administration. After pretreatment with cyclophosphamide 150 mg/kg, groups of 5-10 mice were injected i.p. with quinidine chloride 100 mg/kg on 2 consecutive days, followed by exposure of shaved abdominal skin to UVB 0.1 J/cm2 and UVA 5.0 J/cm2. Five days later challenge was performed on the left ear and on the tail, using the same dose of quinidine and UVA 5.0 J/cm2. The reaction was elevated 24 h later by measuring the increase in ear thickness as well as the wet weight increase of ear and tail. Significant 24 h reactions could be measured using all three evaluation systems. Control animals treated according to the protocol, but not UV-exposed during induction, were negative, thus excluding a phototoxic reaction. The histology of the left ear at challenge showed a round cell infiltrate preferentially of the exposed outer face of the ear consistent with an immunologic reaction. The time course of the reaction showed a maximum at 24 h. Photosensitization to quinidine could be achieved with UVA alone during the induction phase. Quinidine photoallergy can be induced in the mouse after systemic administration, and the reaction measured both at ear and tail. These findings support the assumption that clinical photoreactions to quinidine may have an immunological basis.     

Photoallergy induced by quinidine.

An 82-year-old woman presented with a lichenified dermatitis over light-exposed areas. The eruption cleared upon withdrawal of quinidine and recurred on re-administration of the drug. Though quinidine has not been recognized as a photo-sensitizing agent, upon review of the literature we have uncovered other cases which meet the criteria and justify including this drug among those capable of causing such reactions.     

Systemically induced photoallergy to quinine in the mouse can be elicited topically--and vice versa

Groups of female albino mice were photosensitized and photochallenged to quinine using protocols for either systemic or epicutaneous administration. Compared with control groups, statistically significant inflammatory reactions, measured as wet weight increase in ear tissue, could be obtained both with systemic and epicutaneous administration. Topically induced photoallergy to quinine could be elicited not only by topical, but also by intraperitoneal administration of the drug, and vice versa. The strongest response at challenge was obtained when the induction was performed topically and the challenge by the systemic route. These data suggest that epicutaneous and systemic photoallergy to quinine have mechanisms in common, and that the route of introduction of the sensitizer into the skin is not the crucial factor. This experimental model may be useful in the elucidation of the mechanisms of systemic photoallergy.     

Kaposi sarcoma and quinine: a potentially overlooked triggering factor in millions of Africans

Kaposi sarcoma (KS)-associated herpesvirus, also known as human herpesvirus 8, is necessary but not sufficient for the development of KS. Lytic reactivation of human herpesvirus 8 may be important in KS pathogenesis. KS and its causative agent, KS-associated herpesvirus, have distinctive largely unexplained geographic distributions. We note the recent "oncoweed" hypothesis of biologic plants in the environment accounting for this reactivation. We believe that quinine and its derivatives might better explain the?epidemiology of KS than oncoweeds. Indeed, we propose an "oncodrug" hypothesis, specifically with regard to quinine and its derivatives, a linkage first advanced by one of us (V. R.) and associates in 1984.     

Fixed eruption due to quinine: report of two cases

Fixed eruption is a characteristic condition with recurrent an erythematous macule in the same location. Because fixed eruption is caused by medical drugs in the majority of cases, it is not so difficult to identify suspicious material by interview. However, it may be difficult in cases in which food additives are responsible. We report two rare cases of fixed eruption due to quinine contained in tonic water. In case 1, a 37-year-old man had repeated erythema on the same sites after drinking a variety of cocktails. We suspected tonic water as the causative material. Oral challenge test of tonic water was positive and patch test with quinine sulfate was positive also. In case 2, a 24-year-old woman in had noticed that her eruption appeared after drinking liquor, especially cocktails as in case 1. She was also positive upon an oral challenge test of tonic water and in a patch test of quinine sulfate.     

Persistent light reactivity from systemic quinine

A 41-year-old black female with psoriasis developed photosensitivity and a Koebner reaction while receiving phototherapy. She had been receiving oral quinine intermittently for muscle cramps. Photobiological evaluation revealed a strongly positive photopatch test to quinine sulfate and a marked persistent reduction in the minimal erythema dose to solar-simulated radiation in the uninvolved skin. There were no abnormal reactions to UVA. The photosensitivity is still present 3 years after the withdrawal of quinine. These features are similar to those observed previously in persistent light reactors to topical photosensitizers.     

Photopatch testing negative in systemic quinine phototoxicity

Drug‐induced phototoxicity can be caused by topical or systemic agents and is diagnosed on the basis of clinical history, examination and appropriate investigations. Photopatch testing is the investigation of choice for topical photocontact allergic dermatitis, but its use in drug‐induced phototoxicity has not been validated. We retrospectively analyzed the results of photopatch testing to the drug quinine sulfate in three patients in whom a diagnosis of drug‐induced phototoxicity to this agent had been made. None of the three patients had positive photopatch test reactions at any time point. This demonstrates that in our patients, photopatch testing to quinine sulfate was not a useful additional investigation for diagnosing drug‐induced phototoxicity.     

A Reappraisal of Oral Quinine in Discoid Lupus Erythematosus*

Quinine is described as one of the treatments used for discoid lupus erythaematosus in older text books but this drug has been supplanted in the last 25 years by synthetic antlmalarials. A trial of quinine bisulphate in eleven patients with this condition has been made, for periods up to two years. Half the patients showed improvement, in one case after failure to respond to other standard methods of treatment. Two patients could not take the drug because of nausea, and others showed no effect, or have been lost to follow-up. As the side effects of quinine can be severe, this drug should be reserved for use when more conventional treatment is ineffective or is contraindicated.     

Quinine induced photosensitivity: clinical and experimental studies

Quinine induced photosensitivity, an infrequently described adverse effect, is reported in four patients. The clinical presentation and distribution was that of a light exposed site eruption characterized by oedema and erythema in three patients, and by lichen planus in the fourth. Monochromator phototesting demonstrated abnormal delayed erythema responses in the UVB, UVA and visible wavebands. The clinical features suggested a phototoxic effect but laboratory studies indicated that the molecular mechanisms involved are unusual. Clinical and phototest evidence of abnormal photosensitivity persisted for some months after stopping quinine. Broad spectrum sunscreens are advised for the management of such patients and, where possible, cessation of quinine administration.