Dermal reaction

Some regimens are designed for outpatient administration over much longer time periods and have been used, for example, with allopurinol dermal reactions. Such late-onset morbiliform reactions, sometimes overlapping with erythema multiforme minor, are difficult to evaluate because it is often unclear to what extent the patients were at risk for recurrent reaction. 

Besides the test substance, a positive control substance (a known skin irritant, 1% sodium lauryl sulfate in distilled water) and a negative control (untreated patch) are applied to the skin. When a vehicle is used for diluting, suspending, or moistening the test substance, a vehicle control patch is required, especially if the vehicle is known to cause any toxic dermal reactions or if there is insufficient information about the dermal effects of the vehicle. 

If necrosis is present or the dermal reaction is unusual, the reaction should be described. Severe erythema should receive the maximum score (4), and +N should be used to designate the presence of necrosis and +E the presence of eschar. 

Neuroleptics increase the toxicity of the sunlight to human skin, causing discolorations and other adverse dermal reactions. Researchers noted this phenomenon, called phototoxicity, and set out to study its effects on cells loaded with the neuroleptics fluphenazine, perphenazine, or thioridazine (Bastianon et al., 2005). They found that exposure of these cells to light caused abnormalities in both the plasma membrane and mitochondria. 

Adverse effects observed at therapeutic doses include cough, dermal reactions, blood dyscrasias, bronch-ospasm, and hypogeusia. Angioedema has been reported, but does not appear to be an IgG related immune response. Reversible renal failure has been reported with chronic therapy. Clinical effects that may occur include hypotension with or without a reflex tachycardia, changes in level of consciousness that are directly related to vascular changes, and hyperkalemia. Hyperkalemia can occur as a response to sodium loss. Delayed hypotension, at 19 and 25 h, has been observed following ingestion of captopril. 

Side effects of clonidine therapy include dry mouth, drowsiness, sedation, and constipation. Abrupt discontinuation of therapy may result in a withdrawal syndrome manifested as restless and headache in addition to significant rebound hypertension. Withdrawal can be avoided by tapering therapy over 2-4 days. The incidence of a local dermatitis or an extended dermal reaction with use of the transdermal patch is 15-20%. 

A toxic syndrome consisting of ataxia, hypertonicity, tremor, and clonic jerking, and progressing to coma and seizures, may occur after dermal or oral exposure. Symptoms may occur within 30 min after an acute ingestion. Dermal exposure may cause irritation, sensitization, and erythema. A study with volunteers using 75% DEET showed that 48% had severe dermal reactions at the crease of the elbow but not at other dermal application sites. 

Dermal reactions are seen whereby exposure to a certain chemical causes little effect following initial contact with it but, with repeated (daily, weekly, or even once a month) exposure of the skin, an effect, usually an erythema or red spot, is seen that occurs earlier in time, is more severe, and persists for a longer duration. Subsequent exposures, even though weeks or years apart, result in what appears to be an allergy-like, delayed reaction at the site of exposure or even on parts of the body where no exposure has occurred. The pattern of development of this skin condition, frequently found in the workplace, is suggestive of an allergy. 

Metallic Mercury. Inhalation exposure of individuals to elemental mercury vapors for acute and intermediate durations has resulted in erythematous and pruritic skin rashes (Aronow et al. 1990 Bluhm et al. 1992a Foulds et al. 1987 Karpathios et al. 1991 Schwartz et al. 1992 Sexton et al. 1976). Other dermal reactions to mercury exposure include heavy perspiration (Aronow et al. 1990 Fagala and Wigg 1992 Karpathios et al. 1991 Sexton et al. 1976) and reddened and/or peeling skin on the palms of the hands and soles of the feet (Aronow et al. 1990 Fagala and Wigg 1992 Karpathios et al. 1991). 

Dermal Effects. Dermal reactions have been observed in persons exposed to inorganic and organic mercury following inhalation, oral, and/or dermal exposures. The predominant skin reaction is erythematous and pruritic skin rashes (Al-Mufti et al. 1976 Aronow et al. 1990 Bagley et al. 1987 Biro... 

These products include household and industrial cleaners, cosmetics, and hair treatments. Surfactants contribute to adverse dermal reactions by stripping the oils that protect the skin, leaving the skin more vulnerable to attack by other chemical species. For example, it was found in one study that the simultaneous application of known contact allergens and a surfactant, sodium lauryl sulfate, to the skin results in an enhanced response to the allergens. ... 

Her pharyngitis became progressively worse, leading to inflammation of the eustachian tubes and hearing impairment. Nausea and diarrhea did not occur in a patient who developed severe dermal reactions after taking 2.3 mg/kg/day 2,4-DNP for 14 days (Anderson et al. 1933). 

While in the hospital she also developed symptoms of neuritis and bilateral cataracts, which were not present on admission. Hematological tests were normal except for a slight secondary anemia. This individual may have had an idiosyncratic reaction to 2,4-DNP, dermal reactions in other patients were reversed when 2,4-DNP was discontinued. Oral exposure to 2,4-DNP at 0.01 mg/kg/day would be unlikely to result in effects on ATP production in the mitochondria, which is the mechanism of action for 2,4-DNP-induced toxicity. 

Goldman and Haber 1936). Whether the dermal reactions (including severe urticarial or macropapular lesions) seen in humans after acute-, intermediate-, and chronic-duration oral exposure involve sensitization is unclear. These reactions sometimes disappeared during continuing... 

The treated area is severely inflamed. The atrophic base of the stretch marks stands out and signals the extent of the dermal reaction (Figure 21.13). The controlled inflammation caused by the treatment is essential, as it triggers the skin regeneration processes. 

Acute dermal reactions to 90Sr have been described for depilated skin in mice, guinea pigs, and pigs. In mice, skin exposed to a single 2,000-5,000 rad (20-50 Gy) dose of beta radiation from a 90Sr-90Y source... 

Dermal reactions should be scored on a scale that describes the amount of erythema, edema, and other features indicative of irritations. (See Appendix A for an example of a scoring system that can be used.) The percentage adherence of the transdermal patches should be assessed using a 5-point scale (see Appendix B). 

Paley RG, Tunbridge RE (1952) Dermal reactions to insulin therapy. Diabetes 1 22... 

Table 9.4. Guinea pig sensitization dermal reactions—challenge with X -poly(GGAP), batch CG65PA. ...

Table 9.7. Guinea pig sensitization dermal reactions—Challenge test article X -poly(AVGVP), batches CG20WR and CG156WR. ...

Thus the results of the histological examination do not coincide with the aspect of the macroscopic lesions. However, we should keep in mind that, when we judge a macroscopic reaction, we appreciate only the dermal reactions while with a histological examination, the degree of the epidermal lesions and the nature of the infiltrate are also realized. 

Grimmer (1961) pointed out that if sensitization is carried out through the lymph nodes or the spleen, only a dermal reaction is obtained. Recently this has also been emphasized by Klaschka (1966). The histological picture is different according to the means of sensitization (DNCB) solely dermal lesions (sensitization by intravenous and intraperitoneal injections) or combined dermal and epidermal lesions (epicutaneous applications or intra-cutaneous injections). 

In man, St. Epstein (1952,1956 and 1958) demonstrated tests with neomycin and nickel methiolate, which showed only dermal reactions. For W. Epstein and Kligman (1959), as for others, the dermal reactions precede the epidermal lesions, the lymphocytes play an essential part in the eczematous reaction. 

To summarise it can be said that one finds pure dermal reactions (sensitization with potassium bichromate, passive transfer according to de Weck and Brun (1956) etc.) and pure epidermal reactions (Sato, 1961). It seems that epidermal and dermal reactions are more or less independent of one another. 

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