Contents
Drug rashes are skin changes caused by topical or systemic medications; They are characterized by a variety of clinical symptoms depending on the mechanism of origin and triggering factors. Drug-induced allergy occurs in about 2,2% of all treated patients and increases with age. The ailment affects women much more often than men.
Drug Rashes – Risk Increasing Factors
The incidence of allergic drug reactions among all patients is estimated at 2,2%, it increases with the age of patients (large amount of medications taken, liver and kidney dysfunction); in patients with AIDS, the risk of drug rash increases. Undesirable drug-induced symptoms are more common in women.
Drug rash – the mechanism of its formation
The mechanism of many drug reactions is unknown. It is believed to be based on hapten theorywherein drugs are unable to stimulate an immune response without first attaching to a carrier (blood or tissue protein). Only a few classes of protein drugs used, e.g., xenophyte sera, hormones, enzymes, sera, and immune vaccines, can directly induce an immune response.
Figure 5.28. Drug-induced dermatitis
Classification of adverse drug reactions
Non-immune reactions
1. Type A – predictable (80% of reactions):
a. overdose,
b. side effects,
c. cumulation,
d. delayed toxicity,
e. drug interactions,
f. metabolic disorders,
g. teratogenicity,
h. anaphylactoid reactions,
i. exacerbation of disease symptoms,
j. damage (chromosomal mutations),
k. provocation of existing or hidden skin disease.
2. Type B – unpredictable (20% of reactions); only in susceptible patients.
Immune reactions – types of hypersensitivity reactions according to Gell and Coombs
3. Type I – IgE-dependent:
a.hives,
b. anafi laksa,
c. angioedema,
d. macular rash.
4. Type II – cytotoxic:
a.thrombocytopenic purpura,
b. cytopenias.
5. Type III – immune complexes:
a. serum sickness,
vasculitis,
c. type Arthusa
d. urticaria and anaphi laxia,
e. hemorrhagic and bullous rashes.
6. Type IV – cellular (delayed):
a.contact eczema of the skin,
b. lichenoid reactions,
c. pustular reactions,
d. chronic purpura reactions,
e. pseudolymphoma reactions,
f. permanent drug-induced erythema,
g. measles, pyresis and rubella-like rashes,
h. erythema multiforme.
Other types of reaction:
a.Jarisch-Herxheimer reaction,
b. mononucleosis reaction – ampicillin. Predictable drug reactions (type A) occur in healthy people and are usually dose related. They are the result of the known pharmacological effects of the preparation and also appear after therapeutic doses. Unpredictable (type B) reactions can be genetically determined. They are most often independent of drug action and dose.
The most common drugs: antibiotics – penicillin, ampicillin, amoxicillin and other beta-lactam antibiotics; sulfonamides – trimethoprim- sulfamethaxazole, non-steroidal anti-inflammatory drugs, blood derivatives and mucolytics (75% of reactions), antibacterial agents (42%), antifungal, anti-inflammatory and analgesic agents (27%), drugs affecting the central nervous system.
Drug rashes – symptoms of ailments
Drug rashes may be generalized or limited; they are usually symmetrical and affect different parts of the body. The limbs are usually affected on the extensor side, the changes often affect the mucous membranes and genital areas.
Drug rashes do not have the characteristics of a given drug. Different drugs can cause identical skin lesions. The same drug can cause different morphological reactions; most often erythematous-papular, sometimes resembling disseminated eczema or vascular changes:
- hives blisters,
- lichen-type eruptions,
- blisters
- acne eruptions,
- necrotic changes,
- pigment changes,
- hair, nail and other growth disorders.
Skin eruptions are often accompanied by pruritus of varying degrees of intensity general symptoms (fever, weakness, bronchospasm), symptoms of internal organs (nephritis, anuria, albuminuria, myocarditis, hepatitis), biochemical changes (anemia, leukopenia, thrombocytopenia, eosinophilia). Among patients with adverse drug reactions:
- 33% are patients with persistent erythema reactions,
- 33% with various types of skin rashes,
- 20% of the type of urticaria and vasomotor erythema.
How to recognize drug rashes?
Diagnostics of drug-induced rash mainly includes:
- interview – a well-collected and insightful interview plays an important role in diagnostics – a multi-specialist physical examination,
- additional tests: peripheral blood picture, eosinophilia in peripheral blood and secretions,
- badania in vivo:
1. Epidermal patch tests. It is used for testing contact allergy (Type IV delayed reaction); the most common are PT with drugs used externally: eucerin, lanolin, Peruvian balm, anesthesin, ichthyol, neomycin, gentamicin, bacitracin. Allergens are placed on the surface of the shoulder or intercapular skin; reading after 48, 72, even after 96 hours since foundation. The lymphocytes present in the skin, specifically allergic to a given allergen, are responsible for the reaction. It is a safe test, easy to perform, it does not pose a risk of anaphylactic shock, it may exacerbate the existing foci of the disease. Its disadvantage is low sensitivity, often false negative reactions. Application: diagnostics of persistent erythema, drug purpura.
2. Skin prick tests (SPT). They are used mainly in cases of immediate drug reactions, which proceed with the action of specific IgE antibodies. SPTs are applied to the skin of the inner forearm and require skin pricking. Reading the results 20 minutes after the tests were started. It is recommended to use the drug in a commercially available form without dilution.
3. Intradermal tests (IDT — intradermal tests). They are performed after obtaining a negative SPT result with the suspect drug; Serial dilutions of the test drug are administered intradermally on the inner surface of the forearm in the amount of 0,02-0,05 ml; reading after 30 minutes and 6 and 24 hours IDT is more sensitive than SPT, but false positives are more common. These tests are performed in a hospital; a severe reaction with anaphylactic shock may occur. IDTs are contraindicated in patients with Stevens-Johnson syndrome, TEN (toxic epidermal necrolysis), and a history of leukocytoclastic vasculitis. SPT and IDT are applicable to the evaluation of penicillins, muscle relaxants, hormones, opiates; rather, they are not used in the study of iodine contrast agents, local anesthetics. In Poland, they are performed mainly with penicillin.
In vitro studies:
1. Measurement of the serum concentration of IgE antibodies in specific reactions for a specific drug: R-lactam antibiotics, tetanus toxins, certain hormones, muscle relaxants; by immunological tests, e.g. FEIA. They are mainly performed in patients at risk of developing a severe drug reaction.
2 Lymphocyte transformation test (LTT – lymphocyte test transformation). It is taken into account that drugs can directly stimulate T lymphocytes. This test is mainly used in the diagnosis of generalized drug rash (maculopapular, bullous, pustular), DRESS. LTT is performed with the following drugs:
- antibiotics (beta-lactam, macrolides, tetracyclines),
- antiepileptic drugs
- iodine-based contrast agents,
- anti-tuberculosis drugs,
- local anesthetics (lidocaine, mepivacaine),
- morphine derivatives (pethidine, codeine).
This test is safe for the patient, more sensitive than other tests. The LTT test is performed. only in the period of remission, 4-8 weeks after the onset of drug reaction.
3. Elimination test. It consists in discontinuing medications and observing whether the skin changes are regressing.
4. Provocation tests (DPD. Drug provocation test). Drugs can be administered orally, parenterally, directly on the skin, or otherwise. They are contraindicated in patients who have a history of anaphylactic shock, bullous systemic drug rash, vasculitis, autoimmune disease (systemic lupus, pemphigus vulgaris, cytopenia). In patients with AGEP, Stevens-Johnson syndrome, and a history of TEN, it can be performed. PT.
We perform provocation tests only during hospitalization due to the high risk of the examination. An important issue is the time interval between the drug reaction and the performance of diagnostic tests – after complete recovery, at least one month after the end of therapy.
Drug rashes – what is the prognosis?
The course of drug rashes may be mild or may be life-threatening (toxic epidermal necrolysis). In 0,32-1% of patients a drug reaction is unsuccessful, being the sixth cause of death after heart disease, cancer, strokes, lung diseases and accidents.
Types of severe skin reactions
a. drug-induced erythema multiforme,
b. Stevens-Johnson syndrome,
c. toxic epidermal necrolysis,
d. AGEP,
e. DRESS.
LITERATURE:
1. Col N., Fanale J.E., Kronholm P.: Th e role of medication noncompliance and adverse drug reactions in hospitalizations of the elderly, Arch Int Med 1990, 150, 841-845.
2. Kalish R.S.: Drug eruptions: A review of clinical and immunological features, Adv Dermatol 1991, 6, 22- -37.
3. Brackow K. i wsp.: General considerations for skin test procedures in the diagnosis of drug in the investigations of cutaneous adverse drug reaction, Contact Dermatitis 2001, 45, 321-328. Pichler W.J., Tilch J 4. .: Th e lymphocyte transformation test in the diagnosis of drug hypersensitivity, Allergy 2004, 59, 809-820.
Erythema multiforme (Fig. 5.29)
Erythema multiforme is an edematous, bluish red erythema, well demarcated from the environment, sometimes with blisters on its surface, resulting from an acute allergic reaction. Distinguishes:
a. milder (minor) and severe (major) form,
b. Stevens-Johnson syndrome (SJS),
c. toxic epidermal necrolysis (TEN).
The ailments come from many causes:
a.viral infections (mainly herpes simplex virus),
b. mycoplasmas (pulmonary mycoplasma infections are associated with severe forms of the disease),
c. Drugs: sulfonamides, barbiturates, aspirin, penicillin, tetracyclines, anticonvulsants, allopurinal, NSAIDs, quinine derivatives,
d. streptococcal infections of the upper respiratory tract,
e. bacterial and fungal infections,
f. malignant tumors,
g. some autoimmune diseases (visceral lupus, polyarteritis nodosa, Wegener’s granulomatosis).
Symptoms are lesions of varying intensity depending on the variety.
Figure 5.29. Erythema multiforme
Figure 5.30. Erythema multiforme – mild variety
Erythema multiforme – milder variety (Fig. 5.30)
A milder form of erythema multiforme is the herpes simplex virus infection. In the course of the disease, the lesions are located on the dorsal surface of the proximal parts of the upper and lower limbs. They can appear on the mucous membranes of the mouth (mainly the lips) and genital areas.
Suddenly, symmetrical, erythematous-edematous, ring-shaped eruptions (image of a shooting target) appear. They sometimes show blisters or haemorrhagic changes. Accompanying symptoms – temporary joint and muscle pains, slight temperature increases. Eruptions do not cause any discomfort, they disappear without leaving a trace.
Diagnosis – the disease should be differentiated from pemphi goid and festoon urticaria. The prognosis is good and improves quickly, but there may be relapses.
Erythema multiforme – severe variety (Fig. 5.31)
Severe erythema multiforme occurs due to infection with Mycoplasma and the herpes simplex virus. Illness: torso is involved; there are always changes in the mucous membranes of the mouth, eyes (scarring) and the genital area. Presence of target-type acral lesions with blisters in the center; they occupy less than 10% of the body surface.
The prognosis of the disease: good, relapses in this variant are less frequent.
Figure 5.31. Erythema multiforme – severe variety
Stevens-Johnson syndrome (SJS) (Fig. 5.32)
Stevens-Johnson syndrome (SJS) is mainly caused by drugs: sulfonamides, tetracyclines, penicillins, non-steroidal anti-inflammatory drugs, sometimes herpes simplex virus, mycoplasma or other infections.
symptoms
The lesions always affect the mucous membranes of the mouth, genitals, sometimes the eyes, nose, and the trunk. The onset of Stevens – Johnson’s disease is rapid; there is high fever and joint pains. Duration 3-6 weeks. There are confluent erythema spots on the trunk, blisters occupy less than 10% of the body surface, turn into erosions and accumulated hemorrhagic scabs. There are also eye complications, as well as the creaking and atrophy of the nail plates. It is important to differentiate the syndrome from pemphi goid, pemphigus vulgaris and pemphigus.
How to heal?
Treatment of the disease depends on the etiological factor and the severity of erythema multiforme. Locally: ointments or creams containing corticosteroids. Ogolnie: in milder forms, symptomatic. In the case of an extensive recurrent form, treatment with acyclovir (5 times a day 200 ml for 5 days), followed by a longer period (2-3 times a day) to avoid relapses. Good effects are achieved in the developed disease by administering corticosteroids (60-100 mg / day) with gradual reduction over 3 weeks. Broad-spectrum antibiotics, antihistamines, calcium, vitamin C and more. Erosions within mucosal lesions – soaps or creams with antibacterial agents.
Figure 5.32. Stevens-Johnson syndrome
Toxic epidermal necrolysis (Fig. 5.33)
Toxic epidermal necrolysis is a rare disease. Prevalence in Europe is 1 in 1,3 million people during the year. Women get sick more often.
The reasons
Toxic epidermal necrolysis occurs after the ingestion of a drug administered for an infection. They are most often caused by: antibiotics, sulfa drugs, antimalarials, anticonvulsants and non-steroidal anti-inflammatory drugs. So far, SJS and TEN are little known. This is believed to be a cellular cytotoxic response. The epidermis shows the presence of stimulated lymphocytes. It is not known whether cytotoxic T cells damage the epidermis directly or release cytokines that stimulate apoptosis.
symptoms
The lesions are located in the following areas: face, trunk, extension surfaces of the limbs, oral mucosa, genitals and eyes.
After the prodromal period associated with bacterial or viral infection (fever, runny nose, conjunctivitis), an extensive macular rash appears on the body and face. Includes extension surfaces of the limbs. Within it, large, flaccid blisters form, which, when rubbed, crawl over large spaces (Nikolski’s symptom).
The changes also apply to:
- mucous membranes of the eyes (complications – fusion of the eyelid with the eyeball, blindness);
- the mouth and genitals (difficulty eating, urinating and stools).
The course of toxic epidermal necrolysis is very severe, leads to electrolyte disturbances, complications – acute renal failure, pneumonia and hepatitis – already in the first week of the disease, bacterial infection, including sepsis, hypovolaemia.
The skin heals, sometimes leaving a slight scarring. There is anagenic alopecia with a lot of hair loss. Typical Beau lines appear on the nails, some of them come off and grow back to a limited extent.
Diagnostics
There are no specific tests to confirm the diagnosis of TEN. Electrolytes and renal function should be monitored. In the early stage of the disease – accelerated ESR and increased hematocrit (fluid loss). Recently, LDH (lactic acid dehydrogenase) is believed to be a marker of TEN and SJS severity.
In diagnostics, the disease should be differentiated from: Staphylococcal scalded skin syndrome, graft versus host disease, erythroderma, extensive photoxic reaction, pemphigus vulgaris, pemphigoid.
Treatment
The most important thing is proper care. Patients should be referred to intensive care centers or burn units. The aim of the therapy, as in the case of patients with burns, is to control body temperature, fluid balance, and to prevent secondary bacterial infections. The early treatment of systemic corticosteroids with high doses of corticosteroids remains controversial.
The prognosis is very serious; the mortality rate is over 40%.
Figure 5.33. Toxic necrosis of the epidermis
Acute generalized pustular eruption (Fig. 5.34)
Acute generalized pustular eruption is an acute generalized exanthematous skin bacterial allergy. disappears after a few weeks. The causes of the disease are drugs: mainly antibiotics (beta-lactam, macrolides, tetracyclines, nystatin), quinolones, sulfonamides, non-steroidal anti-inflammatory drugs, painkillers and antipyretics, antimalarials, calcium channel blockers, furosemide, isoniazid. Bacterial (beta-hemolytic streptococcal) or viral infection.
Pathophysiology so far unexplained. The role of immune complexes (features of leukoclastic vasculitis) is considered.
symptoms
Suddenly there is a fever above 38 degrees Celsius, skin lesions of the nature of epidermal pustules on the basis of extensive erythematous changes; initially on the face, gradually on the trunk and limbs. In 25% of patients, erosive changes also appear in the oral cavity and on the tongue.
Diagnosis
Diagnostics reveal accelerated ESR, leukocytosis (even around 10 / ml), sometimes hypocalcaemia, hypoalbuminemia and an increase in liver transaminases. There is a visible presence of intra-epidermal, single-chamber, sterile micro-abscesses in which neutrophils predominate. There are perivascular infiltrates in the dermis.
Pustular rash should be differentiated from:
- pustular psoriasis,
- Sweet’s syndrome,
- erythroderma,
- toxic epidermal necrolysis,
- staphylococcal skin syndrome.
Treatment and prognosis
Acute generalized pustular eruption usually resolves spontaneously, on average after 2-3 weeks. In local treatment, preparations containing corticosteroids are used. In severe cases, corticosteroids are generally used, gradually reducing the dose.
Figure 5.34. Acute generalized pustular eruption
Drug reaction, eosinophilia, systemic symptoms (DRESS)
Syn.: Drug hypersensitivity syndrome (DHS), drug-induced deleyed multiorgan hypersensitivity syndrome (DIDMOHS).
A drug reaction is an extremely severe drug reaction with a serious prognosis, including a triad of symptoms:
- fever,
- skin changes,
- incident of internal organs.
The disease develops within 1-8 weeks of starting the drug. Frequency is rare; one in 10, there is no significant difference in incidence between women and men; more often in black people.
The reasons
The etiological factors are antiepileptic drugs from the group of aromatic compounds: phenytoin, phenobarbital, carbamazepine, sulfones, sulfonamides, allopurinol, antituberculosis drugs. The mechanisms of detoxification of metabolites of the drugs used are damaged. Active drug metabolites bind to histocompatibility antigens on keratinocytes. The lymphocytes producing interleukin 4 and 5 are stimulated or directly to increase the cytotoxic effect of the lymphocytes.
symptoms
Drug reaction begins with prodromal symptoms:
- fever up to 40 degrees Celsius,
- chills,
- pharyngitis,
- enlargement of the lymph nodes.
Skin changes: in about 90% of patients in the first week of the disease, vivid red macular-erythematous rash, then merging into papules, sometimes pustules. The lesions are initially on the face, upper torso, then hug. limbs. More rarely, these are erythema multiforme, Stevens-Johnson syndrome or toxic epidermal necrolysis.
Multiorgan lesions: liver damage occurs within 1-7 weeks; mild to necrotizing, interstitial nephritis; CNS events: encephalitis, interstitial pneumonia, autoimmune thyroiditis; peripheral blood changes: eosinophilia, neutrophilia, neutropenia, thrombocytopenia, haemolytic anemia.
Diagnostics
You need a complete blood count with a smear, liver transaminases, urea, creatinine, chest X-ray, a modified blast transformation test using microsomes, and patch tests. In addition, the drug reaction should be differentiated from: acute viral infection; viral hepatitis, malignant lymphoma, influenza; connective tissue diseases; post-serum sickness.
Treatment
The drug that caused the symptoms must be discontinued immediately. Systemic glucocorticosteroids (0,5-1 mg / kg bw), used according to the clinical condition and laboratory tests, in order to prevent disease recurrence. Some recommend intravenous immunoglobulins or plasmapheresis.
The prognosis of the disease is serious – mortality approx. 10%.
Maculopapular rash
Macular and papular rashes are the most common drug reaction in elderly people; while in children, the organism is often associated with viral infections. The most common cause of ailments is:
- penicillin,
- ampicillin,
- allopurinol,
- sulfonamidy,
- fenylbutazon,
- gentamicin,
- gold preparations;
- less often cephalosporins,
- barbiturany,
- thiazides,
- erythromycin,
- pyrazolone and tetracycline derivatives.
Approximately 100% of patients with mononucleosis develop a macular rash after administration of ampicillin or amoxicillin. Changes of this type in approximately 60% of HIV patients who received trimethoprim – sulfamethaxazole. In addition, there is a delayed reaction to type IV drugs (according to Gell and Coombs), in allergic patients it appears after 2-3 days, and in non-allergic patients usually after 9-10 days. Ampicillin causes drug eruptions within 14 days of first exposure.
symptoms
The lesions usually affect the limbs and trunk; the face remains free of efflorescence. In the course of the disease, maculopapular eruptions of various sizes and shapes appear, usually numerous, symmetrical, with various locations, and sometimes erosive lesions of the oral mucosa. General symptoms of maculopapular rash:
- slight fever
- itchy skin.
Eruptions disappear after about 2 weeks with exfoliation and, sometimes, post-inflammatory discoloration.
Diagnostics
Disclosure is Eosinophilia in the peripheral blood serum. It should be remembered to differentiate the disease from: pink dandruff, rash in the course of viral infections, generalized contact eczema and secondary syphilis.
How to heal?
It is necessary to discontinue the drug suspected of causing skin lesions and possibly switch to preparations belonging to a different chemical group. Locally: corticosteroid ointments or creams with an appropriate base. Ogolnie: in case of severe changes, consider administration of systemic corticosteroids; antihistamines.
Plamica
Purpura occurs as a result of extravasation to the skin or mucous membranes. It can develop as a result of:
- platelet function disorders (aspirin),
- disorders of coagulation processes (anticoagulants) or allergic thrombocytopenia (heparin, quinine, quinidine, chlorthiazide) and non-allergic (cytostatics),
- vascular causes (steroids, phenacetin, meprobamate).
Figure 5.35. Hypoallergenic purpura
Symptomatic thrombocytopenic purpura
Symptomatic thrombocytopenic purpura is characterized by extravasation into the skin, subcutaneous tissue or mucous membranes. The causes of the formation are usually drugs: most often – sulfonamides, salicylates, chloramphenicol, hypnotics and sedatives (phenylbarbituric acid derivatives) and phenothiazines. Thrombocytopenic purpura may be accompanied by:
- cancer
- systemic diseases,
- sepsis,
- infectious diseases.
Hypergic purpura (Fig. 5.35)
Hypergic purpura (allergic vasculitis, leukocytoclastic vasculitis) is a disseminated multiforme and hemorrhagic eruption, in some cases with necrotic tissue breakdown, arising as a result of the inflammatory process of capillaries, small veins and arterioles with the deposition of immunoglobulins and complement in them. The disease occurs with the same frequency in both men and women.
The etiological factors include exogenous antigens: microorganisms; drugs: antibacterial preparations, especially beta-lactam antibiotics and sulfonamides (10% cf), ACE inhibitors, phenytoin, non-steroidal anti-inflammatory drugs, thiouracils; endogenous antigens: DNA (systemic lupus), immunoglobulin (rheumatoid arthritis), tumor antigens.
Pathofizjologia
The pathophysiology of hypergic purpura is complex, it is an incompletely understood disease associated with the third allergic mechanism. Immune complexes are formed, which build up in the wall of blood vessels, activate complement, and attract granulocytes and macrophages to the vascular wall. Activated neutrophils produce proteolytic enzymes and are also a source of free oxygen radicals that damage the vascular endothelium and surrounding tissues. T lymphocytes are activated, releasing pro-inflammatory cytokines.
symptoms
The lesions most often occur on the extension surfaces of the lower limbs in walking people and in the sacrum region in lying people; they may occupy the distal parts of the upper limbs and the torso. In the initial stage of purpura, the eruptions are palpable hemorrhagic macular changes, then they appear hives, lumps, lumps, vesicles with centrally visible decay, livedo reticularis. Ulcers may form with an inflammatory reaction around them. General symptoms: fever and joint pain. The skin lesions are sometimes accompanied by the involvement of internal organs (lungs, gastrointestinal tract and kidneys).
Diagnostics
Hist: The test should be performed within 24 hours. from the appearance of purpura on the skin. It plays an important role in diagnostics. Leukocytoclastic vasculitis lesion with various types of necrosis of the walls and surrounding vessels (edema of endothelial cells, intravascular fibrinous necrosis and perihedral cellular infiltration of neutrophils and cell nuclei fragments: often lymphocytic extravasation, vessels are dilated with thrombi.
There is also a direct immunopathological examination of the skin (DIF) for the presence of immunological complexes with class M immunoglobulins.
Treatment
Topical corticosteroid preparations are administered, moreover, it is necessary to discontinue the suspicious drug. In turn, the following are generally administered: antihistamines, injections of vit. C and calcium salts and corticosteroids in gradually reduced doses. The prognosis for hypergic purpura is different, the worst prognosis is cases involving the kidneys and the gastrointestinal tract.
Drug-induced erythroderma
Drug-induced erythroderma is one of the more severe drug-induced skin reactions of various etiologies, it is a generalized inflammation of the skin. The cause of the disease are general and topical medications: antibiotics – penicillin, ampicillin, sulfonamides, antimalarials, salicylates, heavy metal salts, tranquilizers, barbituric acid derivatives; less often – isoniazid, streptomycin, griseofulvin, hydantoin, captopril, cimetidine.
symptoms
Many weeks after the start of therapy, a blotchy rash appears on the skin, which merges into erythroderma. The skin is deeply red, very profusely, it peels off almost over the entire surface, and thickens with time. If erythroderma continues for some time, it leads to hypothermia, dehydration, and fluid and electrolyte disturbances.
In addition, the basal metabolism increases and hypoalbuminemia occurs, the levels of iron and folic acid decrease (anemia). There are cardiovascular, renal and hepatic complications, gastrointestinal bleeding and venous clots.
Treatment
Significant improvement in drug-induced erythroderma is observed following the identification and discontinuation of the drug causing the disease. However, symptoms of the disease may persist for several weeks.
Pseudomycotic drug reactions (pseudolymphoma)
Drug-induced pseudo-tumors are a hypersensitivity syndrome, a group of clinical symptoms resembling benign lesions of the lymphoma type, associated with T-type pseudo-fibroids. Moreover, it is a rare disease, most often in patients over 60 years of age. The frequency of occurrence regardless of the sex of the patient.
The causes of the ailments are:
a. antibiotics: penicillin, flucloxacillin;
b. antidepressants: fluoxetine, lithium, doxepin, amitriptyline;
c. antihistamines: H1 blockers – diphenhydramine, H2 – cimetidine, ranitidine;
d. antihypertensive drugs of different target point: captopril, enalapril, lizinopril, atenolol, diltiazem, verapamil, clonidina, valsartan, hydralazine, diuretics – hydrochlorothiazide, dapsone, sulfonamides, anticoagulants;
e. psychotropic drugs (chlorpromazine, thioridazine, benzodiazepines; clonazepam, clorazepam);
f. chemioterapeutyki: cyklosporyna, metothotrexat, imatinib (Glivec), oxaliplatin/5- fl uorouracyl/leukovorin;
g. anti-rheumatic drugs: statins, steroid hormones – estrogen, progesterone;
h. vaccines: hepatitis A and B vaccine;
i. anticoagulants: topical agents, essential vegetable oils, menthol and hydroquinone cream.
The onset of a drug reaction may occur many months after the start of therapy; lesions have been described after five years of treatment.
symptoms
Approximately 80% of patients develop a morbilliform rash, fusing with purpura, edema and vesicles. In addition, there is enlargement of the lymph nodes, fever, joint pain, hepatosplenomegaly, hepatic dysfunction, and interstitial nephritis.
Diagnostics
Hist .: Pseudolymphoma with lymphocytic infiltrate, often atypical cells and epidermotropism; reactive changes in the lymph nodes. Monitoring of liver and kidney function is important, peripheral blood counts: eosinophilia higher than 1000 / mm3.
Treatment
All suspected medications must be discontinued in the treatment of pseudo-tumors. Topical steroid ointments and creams are used until the lesions have resolved.
Urticaria reactions (Fig. 5.36)
Nettle-type reactions are drug-induced reactions in which shedding of urticarial blisters occur. The changes may be accompanied by angioedema. These reactions account for about 80% of all drug-induced changes in hypersensitivity.
types
Depending on the division, drug-induced urticaria may be:
- spicy,
- chronic,
- recurrent (less common),
- allergic and pseudoallergenic.
symptoms
In the course of an urticarial reaction, hives of various sizes, shapes and colors appear on the skin within a few minutes. The lesions are accompanied by itching, and the eruptions quickly disappear without leaving a trace. In addition, chronic urticaria may lead to discoloration of the skin (urticaria cum pigmentatione).
Medicines are rarely the cause of this type of disease. It can last from several weeks to several years. In Type III allergic urticaria, wheals initially appear on the sides of the hands and feet. Skin changes are accompanied by:
- fever,
- arthritis,
- enlargement of the lymph nodes.
The clinical picture in contact urticaria is quite characteristic. Skin changes occur quickly at the point of contact with the allergen.
Acute non-immune urticaria occurs with systemic symptoms, i.e. conjunctiva, nasal and respiratory symptoms. It has the nature of paroxysmal erythema; the changes mainly affect the upper body and are accompanied by severe itching of the scalp. Contact hives disappear within a few hours.
Urticaria may accompany a significant percentage of patients angioedema. These are swellings of the subcutaneous or submucosal tissue, and even the deeper layers of the dermis. The skin within them is unchanged, pale; the patient does not report itching. It most often occurs on the face (lips, eyelids, around the eye sockets), in the genital area, on the proximal parts of the limbs. Involvement of the tongue and larynx causes hoarseness, difficulty swallowing, and shortness of breath (immediate life-threatening). The angioedema disappears within 12 hours.
Diagnostics
1. Allergic urticaria – moderate and chronic:
a. insightful interview,
b. determination of total IgE level, determination of specific IgE for suspected allergens (RAST test),
c. elimination diet (mainly in chronic urticaria),
d. point tests.
2. Serum sickness urticaria:
a. intradermal test in patients who received antiserum in the past.
3. Aspirin urticaria:
a. elimination diets,
b. provocation test (administration of increasing doses of acetylsalicylic acid orally under medical supervision in a hospital setting).
4. Contact urticaria:
a.challenge test,
b. RAST,
c. point tests,
d. skin tests.
Treatment
In the treatment of the disease, it is important to discontinue the suspect medication. Antihistamines, corticosteroids depending on the type of urticaria (in acute, chronic – small pulses, drugs of choice in serum urticaria), mast cell stabilizing drugs, vascular exfoliants (calcium and vitamin C preparations), sometimes psychotropic drugs – in cooperation with a psychiatrist , elimination diet.
Note: Semisuccinate intolerance exists in patients who cannot tolerate acetylsalicylic acid. Another glucocorticoid should be given in place of the hydrocortisone semisuccinate.
Figure 5.36. Urticaria drug reaction
Drug blistering reactions
The blister reaction to drugs is drug-induced vesicular and bullous lesions of varying extent and layout, or causing skin diseases, such as:
- pemphigus, pemphi – goid,
- linear IgA pęcherzowa dermatosis (LABD),
- persistent bullous erythema,
- bullous exudative erythema,
- Stevens-Johnson syndrome,
- toxic epidermal necrolysis.
Etiological factors of the bullous reaction to drugs: penicillamine, captopril; bullous pemphi goid: antihypertensive and diuretic drugs (furosemide), PUVA, X rays; nalidixic acid, piroxicam, rifampicin, sulfonamides, sulfosalazine, NSAIDs. The sulfhydryl groups of drugs react with the sulfhydrol groups of desmoglein. They induce acantholysis without the participation of antibodies.
Treatment
Discontinuation of the drug causing the disease is essential. The type of procedure is implemented depending on the type of disease.
Persistent erythema (Fig. 5.37)
Permanent erythema is recurrent, most often single skin lesions of brown color, appearing in the same location after taking a drug that is not tolerated by a given person. Permanent erythema may occur at different stages of life, in both sexes, most often in the third decade of life.
The reasons
The factors causing persistent erythema are drugs used in a given region of the world (so far 120 drugs causing persistent erythema have been described). Most often these are antibacterial agents – sulfonamides, antibiotics: tetracyclines, penicillin, ampicillin, amoxicillin, nystatin, erythromycin, clarithromycin, clindamycin, griseofulvin, fluconazole, non-steroidal anti-inflammatory agents, antipyretic agents (aspirin, pyrogensin, antipyretics, pyrahamolone derivatives, parbitacetrazolone) propranolol, cimetidine, omeprazole, codeine, chlorhexidine. One or more drugs, even more than 10, can be an etiological factor.
symptoms
The lesions in the course of erythema can be found anywhere on the skin and mucous membranes. More often they are limbs, hands, feet, oral mucosa, genital area and anus. The pathophysiology is unexplained and the role of delayed allergy is assumed. CD8 suppressor-cytotoxic T lymphocytes play a major role in the period of permanent bloom. T lymphocytes have the ability to recognize altered antigens where there was previously a skin lesion. The nonspecific serum factor plays a minor role.
One or more erythematous spots appear in the disease, very clearly demarcated from the environment, with a brown color, appearing constantly in the same places after taking a specific drug. Rarely, eruptions are blistering; they may then occupy the mucous membranes. The skin lesions are generally not associated with general symptoms. In some cases, women experience itching in the vulva area, less often pain.
After each sowing skin lesions occur refractory period (refractors time), during which disease recurrences cannot be expected (up to several months). The erythema lasts for a short time (several days) and disappears with long-lasting discoloration. Discontinuation of the drug does not cause the discoloration to immediately regress.
Diagnosis
Systemic provocations following oral administration of the drug are very sensitive, but various systemic reactions may occur. A positive reaction is evidenced by the appearance of the efflorescence exactly at the site of the original lesion. Local provocation (patch tests, epidermal tests) – the tested drug is applied once as 10% in petroleum jelly or in ethanol, mainly in the area of discoloration after the previous incident; the results are read out every 24 hours – this is not a very sensitive method.
Permanent erythema should be differentiated from:
- post-inflammatory discoloration,
- flat pigmented birthmarks,
- lichen planus pigmentosa.
Treatment is based on the discontinuation of the drug causing the lesions.
Figure 5.37. Persistent erythema
Nodular erythema (Fig. 5.38)
Erythema nodosum are acutely inflammatory, painful bumps located mainly on the anterior surface of the lower leg, do not break down and disappear without scarring. The etiological factor is heterogeneous:
- bacterial infections: mainly streptococci and Yersinia enterocolica, tuberculosis mycobacteria – especially in cases of primary parietal infection in children, in sarcoidosis (Löfgren’s syndrome);
- viral infections (e.g. infectious mononucleosis); toxoplasmosis;
- drugs: most often sulfonamides, salicylates, tetracyclines, painkillers and antipyretics, gestagens, bromides, iodides and gold salts; is sometimes associated with Crohn’s disease and ulcerative enteritis; idiopathic form after excluding other causes.
symptoms
The lesions in the course of erythema nodosum occur most frequently on the extensor side of the lower leg. Single lesions on the thighs and forearms. Multiple lumpy eruptions appear, initially vivid red, with a diameter of several to several centimeters, then bluish-red and brownish in color, with no tendency to decay.
Comorbid symptoms: joint pain, increase in temperature. Duration 2-6 weeks. More common in spring and autumn, sometimes with relapses.
Diagnostics and treatment
Erythema nodosum should be differentiated from: erysipelas, superficial thrombophlebitis and nodular vasculitis. In local treatment, compresses with 2% ichthyol and ointments containing heparinoids are used. In turn, the general therapy depends on the triggering factors; broad-spectrum antibiotics or discontinuation of the suspect drug. Corticosteroids in Löfgren’s syndrome, anti-tuberculosis treatment in paraval tuberculous lesions.
Figure 5.38. Nodular erythema
Lichenoid reactions
Lichenoid reactions are drug reactions that resemble lichen planus in terms of clinical or histology. The triggering factors are:
- gold preparations,
- beta blockers,
- spironolactone,
- captopril,
- antihypertensive drugs,
- Xartan + chydrochlorotiazyd,
- antimalarial preparations,
- acetylsalicylic acid,
- penicillamine,
- cinnarizina,
- non-steroidal anti-inflammatory drugs,
- Ursofalk,
- anabolics,
- acyclovir,
- levamizol,
- methyldopa,
- vaccine against hepatitis B,
- Viagra,
- topically tacrolimus.
Pathological changes occur after a longer period of therapy – after weeks or even months. A delayed reaction occurs, mediated by T lymphocytes. The drug, as a hapten, creates an antigen and binds to proteins of the epidermis. The changes appear after a long period of using the drug.
symptoms
The most common lesions are the trunk, the spines of the hands and feet, the mucous membranes and the genital area are less frequently affected. There are papular eruptions, less monomorphic than typical lichen planus; sometimes exfoliation and scabs.
Diagnostics
Histopathology may be of little help in differentiation, the picture may be similar to that of lichen planus. A thickened granular layer is less often visible. Treatment is based on the discontinuation of the suspect drug.
Acne-like rash
An acne-like rash is a drug-induced rash of the so-called caused by acne. The cause of the ailments are hormones: corticosteroids, androgens, ACTH, anabolics, antiepileptics (phenytoin), contraceptives, anti-tuberculosis agents, lithium salts, anesthetic preparations, halogen, tetracycline, vitamin B12, high doses of vitamin B6, chlorides, bromides, PU iodides and ionizing radiation.
There is a type III allergic reaction. The development of changes is also influenced by the secretion of drugs by the sebaceous glands and irritation of the surrounding skin.
symptoms
In the course of acne-like rash, there are papular-pustular eruptions, localized parietal, without the presence of comedones. The ailment should be differentiated from acne vulgaris and purulent inflammation of the hair follicles.
Drug-induced pigmentary changes
Drug-induced pigmentation changes are changes in the color of the skin, mucous membranes, hair and nails, of a hyper- or hypopigmentation nature, caused by the action of drugs:
a.antibiotics: tetracycline, minocycline,
b. antimalarials; heavy metals (gold salts),
c. leomycin, busulfan, fluorouracil, methotrexate, cyclophosphamide,
d. oral contraceptives,
and. phenothiazyny.
symptoms
Discoloration appears in the course of the disease: phenytoin and its derivatives, oral contraceptives – Chloasma changes in 10% of patients, mainly women (eruptions on the face, neck and shoulder area); last a long time.
The changes in the color of the skin to gray, brown and blue are due to the action of the drug, light and the pigment system. Phenothiazines form complexes with melanosomes – a gray-blue color of the skin in exposed places, exposed to sunlight.
Antimalarials (similar mechanism and place of occurrence) – bluish discoloration, often on the shins and mucous membranes of the mouth.
Tetracyclines, especially minocycline – most often blue-gray discoloration in the place of sun exposure, skin pigmented osteomas, discoloration of scars. The mechanism of changes depends on the chelation of tetracycline with heme compounds.
Chemotherapeutic agents – limited or disseminated changes:
a. 5-fl uorouracil – post-inflammatory discoloration,
b. busulfan – disseminated discoloration, especially intense around the nipples,
c. bleomecin, cyclophosphamide – discoloration of the distal parts of the limbs. Discoloration results from the use of topical retinoids, azelaic acid, focal corticosteroids, para-aminobenzoic acid, interleukin 2. Hair discoloration is caused by: arechine, benzoyl peroxide.
Source: Dermatology Doctor’s Guide, Czelej Publishing House