Cortical follicular atrophy

Introduction Cortical follicular atrophy is one of the clinical symptoms of pathological anatomy in patients with bullous epidermal necrolysis. This is the first type of drug rash we saw in China in 1958. It is relatively rare in clinical practice, but it is quite serious. The onset is urgent, and the rash spreads throughout the body within 2 to 3 days. Initially bright red or purple red spots. Sometimes it is erythematous when it starts to appear, and then expands and expands into a brown-red block. A clinical manifestation of drug allergy.

Cause

The etiological mechanism of drug reactions is quite complex, allergic, non-allergic or other special mechanisms.

(A) allergic reactions Most drug eruptions occur related to this. The main basis is:

1 almost all of the doses allowed by pharmacology.

2 has a certain incubation period.

3 patients are only allergic to certain drugs or certain types of drugs and are highly specific.

4 If a drug has been sensitized, if the same drug is used again, even a small amount often causes the drug rash to recur.

5 Cross-allergy may occur with drugs that are similar in structure to sensitizing drugs.

6 With a sensitizing drug for a skin test, a positive result can be obtained.

7 A small amount of drug-induced rash caused by type I reaction can be desensitized for a short time.

8 anti-allergic drugs, especially corticosteroid treatments are commonly effective.

Chemical drugs are mostly haptens. After entering the body, they must first covalently bind to certain protein components in the tissue to become a whole antigen (hapten-carrier complex). The antigenicity of a drug is related to its own chemical structure. It is generally considered that a drug with a high molecular weight or a nucleus or a pyrimidine nucleus is highly antigenic, such as penicillin G and its derivatives, multimers, and long-acting sulfonamides. Drug eruptions caused by phenobarbital, compound aspirin, etc. are more common; drugs with weak or no antigenicity, such as potassium chloride and sodium bicarbonate, rarely cause or cause drug eruption.

Allergic drug reactions vary in type, and can be expressed in any type I to IV, sometimes in the same patient.

(2) Non-allergic reactions and others

1. Toxic effect: mostly due to excessive dosage, such as central nervous system inhibition caused by high dose of barbiturate hypnotic drugs; bone marrow suppression or liver damage caused by nitrogen mustard, white blood, etc.; poisoning caused by absorption of pesticides 1059 and 1605 Reaction, etc.

2. Pharmacological effects: such as drowsiness caused by antihistamines; euphoria caused by corticosteroids; facial flushing caused by niacin.

3. Light-sensing effect: After taking chlorpromazine or sulfa drugs, it can be exposed to sunlight, which can cause dermatitis mainly in exposed parts. According to its mechanism, there are two kinds of photoallergic and phototoxic reactions.

4. Disturbance of the enzyme system: such as Dalunding can cause oral ulcers by interfering with the absorption and metabolism of folate; 13-cis-vitamin A can change the metabolism of yellow blood caused by lipid metabolism; isoniazid can affect the metabolism of vitamin B6 Causes polyneuritis.

5. Sedimentation: reactions caused by deposition of drugs or their products in special tissues, such as barium, mercury, silver, lead and other heavy metal salts deposited on the gums, arsenic deposits on the skin (pigmentation, keratinization), and a flat Caused by yellowing of the skin.

6. Special local stimulating effects: For example, aspirin can directly corrode gastric mucosa, causing gastric bleeding and gastric ulcer; sulfa crystals block renal tubules, renal pelvis and tube, causing dysuria, hematuria, oliguria and even urinary closure.

7. Flora imbalance: The normal flora in the human body can be mutually suitable in the process of co-evolution for many years. Some flora can inhibit the overgrowth of other flora, and some flora can still synthesize vitamin B and vitamin K for The body needs health. In short, between microorganisms and microorganisms, microbes and the body have reached a contradiction. However, if long-term or large-scale use of antibiotics, corticosteroids or immunosuppressive agents can disrupt these balances. For example, the application of broad-spectrum antibiotics can often lead to the infection of conditional pathogens.

8. Teratogenic and carcinogenic effects: Some drugs may have teratogenic and carcinogenic effects after long-term application, such as thalidomide and trestin.

(III) Influencing factors: In addition to the above-mentioned drugs as direct pathogenic factors and their possible pathogenic mechanisms, the following factors often play a role in the occurrence and development of drug reactions.

1. Drug use

(1) Abuse: Most of them are due to the lack of strict use of the principles of physician medication and random administration. Part of this is due to the patient's ill-advised use of self-contained drugs or self-purchased drugs to cause drug reactions.

(2) Misuse: The doctor prescribes the wrong prescription, or the pharmacy sends the wrong medicine, or the patient mistakes the medicine. Of course, these are accidental events.

(3) Suicide by taking drugs: This is a rare phenomenon.

(4) Dosage: If the dosage is too large, it may cause serious or even death. However, sometimes the drug response may occur in normal doses, which is related to the different absorption, metabolism and excretion rates of different individuals, especially in elderly patients.

(5) medication course; acute illness, medication time is generally not long, even if the drug used is more toxic, its harmfulness may be less. However, in chronic diseases, especially in patients with cancer, the anticancer drugs used have a longer course of treatment, and the accumulation of drugs often occurs, resulting in toxicity. Of course, there are also some drugs such as sleeping pills, sedatives, etc., which can be used for long-term repeated use and can cause drug addiction.

(6) Too many types of drugs: For those who have an allergic system, the more types of drugs are used, the more opportunities there are for reactions. This may be due to cross-reactions between drugs, or synergistic effects.

(7) route of administration: It is generally believed that drugs are more likely to cause a reaction than injection by injection. The surrogate rate of externally used antigenic ointments, such as sulfonamides and tetracycline ointments, is much higher than that of oral administration. Cases of wet application of boric acid solution for external use caused by excessive drug absorption have been reported. A drug taken by a pregnant or lactating woman can cause a reaction in the fetus or infant.

(8) Cross-allergy: Many drugs that have structural differences, such as sulfa drugs containing common "aniline" cores, general-purpose ruthenium, and salicylic acid, can cause the same reaction, called cross-allergy. This reaction can take place within about 10 hours of the first administration without the need for an incubation period of 4 to 5 days or more.

(9) Reuse of sensitizing drugs: If the patient has become allergic to a certain drug and then repeatedly apply it, a more serious reaction may occur. The reuse of sensitizing drugs is usually due to:

1 The doctor's negligence did not understand the patient's past drug reaction history.

2 The patient did not take the initiative to tell the doctor about his history of drug allergy.

3 used a drug that can cause cross-allergy.

4 Individual patients with drug rash in high-sensitivity state are prone to allergic reactions to drugs that are not sensitive.

(10) Syringe is dirty: Unclean syringes, needles, syringes, vials, skin tubes, etc. may cause adverse reactions due to the introduction of certain pyrogens into the body.

2. Body situation

(1) Gender: The drug response can be surnamed for both men and women, but the male is slightly more than the female (3:2). Due to gender differences, estrogen and griseofulvin can cause gynecomastia in males, while androgens cause masculinization in female patients.

(2) Age: Children are more resistant to general drugs than adults who are sensitive to anesthetics. Children's allergic reactions to drugs are also rare.

(3) Idiosyncrasy: an abnormal reaction to a drug that does not occur through an immune mechanism. The cause is unknown.

(4) Genetic factors: Patients with a genetic allergic (atopy) constitution have a potential risk of serious reactions to penicillins.

(5) Allergic or allergic constitution: Most drug reactions occur in patients with certain allergic constitution. Its allergic pathogenesis has been discussed previously.

an examination

Related inspection

Urine routine blood routine

[clinical manifestations]

Because the drug reaction can affect a variety of systems and organs, a wide range, both systemic and local. This section only discusses some typical drug eruptions and a few specific types of drug reactions.

(A) allergic drug rash: This is the most common and most common type of drug rash. According to its incubation period, development, rash performance and outcome, it can be divided into at least 10 subtypes, such as fixed erythema, scarlet fever erythema, measles erythema, urticaria, polymorphous erythema, nodular erythema It is necessary, rose rash, purpura and bullous epidermis necrosis. They have the following in common:

1 has a certain incubation period, generally 4 to 20 days, an average of 7 to 8 days, if it has been sensitized, again with the same drug, often in 24 hours, an average of 7 to 8 hours can occur. The shortest is only a few minutes, and the late is no more than 72 hours;

2 Most of the onset is sudden, and may have prodromal symptoms such as chills, discomfort, and fever;

3 rash developed, in addition to fixed erythema, as usual, generalized and symmetric distribution; 4 often accompanied by systemic reactions of light and heavy, light can be not obvious, heavy can be headache, chills, high fever, etc.;

5 The course of disease has a certain self-limiting, the light is in a week or so, and the severe one is not more than one month; 6 except for the prognosis of blister epidermal necrolysis, the residual is better. Several representative subtypes are described below.

1. Immobilized erythema (fixed rash): It is the most common type of drug rash. According to statistics, it accounts for 22% to 44% of drug eruptions. Among the 909 drug eruptions, 318 cases are 34.98%. Common pathogenic drugs are sulfonamides (long-acting sulfonamides), antipyretic analgesics, tetracyclines and sedative edema patches, round or oval, with clear edges and one or several blisters on severe spots. Or bullae. The number of red spots varies from one to several and the distribution is asymmetrical. Can occur in any part, often occurs at the junction of the skin and mucous membranes such as the lips and external genitalia, often caused by friction caused by erosion. If recurrence, it usually still occurs in the original place, completely or partially overlapping with the pigmentation spots left in the previous time, and often enlarges and increases compared with the previous one. Local lesions may be associated with itching, and there are varying degrees of fever between the skin lesions. After the erythema fades, the purple-brown pigmentation spots of the Ming Dynasty are often left behind, which has not been retired for many years and has diagnostic value. A small number of edematous erythema without purple will fade quickly and leave no trace. Individual cases may be associated with polymorphous erythema, urticaria or measles-like erythema.

2. Scarlet fever-like erythema: The rash occurs suddenly, often accompanied by chills, fever (38 ° C or more), headache, general malaise and so on. The rash begins with large and small erythema. It develops from the face, neck, and upper limbs to the lower extremities. It can be spread throughout the body in 24 hours. The distribution is symmetrical, edematous, bright red, and the pressure can fade. Later, the rash is enlarged and enlarged, and it can be integrated with each other, which can affect the entire skin and resembles scarlet fever. However, the patient is generally in good condition and has no other manifestations of scarlet fever. After the rash develops to a climax, the redness and swelling disappear, followed by large-scale desquamation. After the body temperature, the scales become thinner and thinner, less like sputum, and the skin returns to normal. The whole course of disease is no more than one month, and there is generally no visceral damage. If the rash is like measles, it is called a pityriasis-like drug eruption;

3. Severe polymorphic erythema (Stevens-Johnso syndrome): This is a serious bullous polymorphic erythema. In addition to skin damage, severe mucosal damage occurs in the eyes, mouth and external genitals, and there is obvious sputum and exudation. Often accompanied by chills and high fever. Can also be complicated by bronchitis, pneumonia, pleural effusion and kidney damage. Eye damage can lead to blindness. Children with this type of drug eruption are more common. However, it must be pointed out that this syndrome is sometimes not caused by drugs.

4. Bullous epidermal necrolysis and drug-breaking drug eruption: This is the first type of drug eruption we saw in China in 1958. It is relatively rare in clinical practice, but it is quite serious. The onset is urgent, and the rash spreads throughout the body within 2 to 3 days. Initially bright red or purple red spots. Sometimes it is erythematous when it starts to appear, and then expands and expands into a brown-red block. In severe cases, the mucous membranes are involved at the same time. Loose bullae appear on large pieces, forming many parallel folds of 3 to 10 cm long, which can be pushed from one place to another. The epidermis is extremely thin and slightly rubbed and broken, showing obvious acantholytic phenomenon. The whole body is often accompanied by high heat of around 40 °C. In severe cases, the stomach, intestines, liver, kidney, heart, brain and other organs can be involved at the same time or in succession. I have seen a case of a patient who died of this disease, and the mucous membrane of the nasal feeding tube is densely detached. The course of the disease has a certain self-limiting, and the rash often begins to subside after 2 to 4 weeks. If serious complications occur or serious involvement of some important organs, or due to improper treatment, you can die in about 2 weeks.

The total number of white blood cells is more than 10 × 109 / L (10000 / mm3), neutrophils are about 80%, and the absolute count of eosinophils is 0 or very low. Pathological anatomy of severe death cases:

1 The epidermis was significantly atrophied, and only one to two layers of the acanthosis cells disappeared completely, intercellular and intracellular edema, dermal congestion and edema, infiltration of small round cells in the surrounding tube, and collagen fibers broken. Oral mucosal lesions are similar to the skin.

2 lymph node enlargement, medulla hyperplasia, endothelial mucosal hyperplasia, cortical follicle atrophy.

3 liver section yellow and red, can see blood stasis, and liver cells become more and more. Microscopic examination showed that the upper part of the upper part of the foot was severely sputum, residual hepatocyte lipids and dissociation; the liver parenchyma and the portal were unclear, and some hepatocyte boundaries were blurred, and some necrosis dissolved and was absorbed.

4 The kidney section is swollen and the capsule is everted. Microscopic examination showed vascular congestion, curved edema, and focal infiltration of lymphocytes and monocytes in the cortical stroma.

5 The gray matter cells of the gray matter are variously degenerated, and the occipital nerve cells are water-like degeneration and swelling, and there are satellite cells between them. Basal nucleus and microglia foci-like hyperplasia.

6 Myocardium has interstitial edema and diffuse mild incomplete cell infiltration.

The bullous epidermis of the bad-skinned drug eruption is similar to the toxic epidermal necrolysis reported by Lyell (1956). The latter lesion is like a scald, not necessarily bullous. Local pain is obvious, no obvious visceral damage, and often recurrence. But some people think that the two may be the same disease.

(2) Other types of drug eruptions and drug reactions: The cause is not completely clear. There are many types, and those who choose them are described as follows:

1. Systemic exfoliative dermatitis type: It is one of the more serious types of drug eruption, and its severity is second only to bullous epidermal necrolysis-like drug eruption. In the age of corticosteroids, the mortality rate is very high. Because of the large dose or long course of treatment for this type of drug eruption, it may be combined with a certain toxic reaction based on the allergic reaction.

This type of drug rash is not common. According to incomplete statistics of our department, 909 cases of drug rash accounted for 2.53% from 1949 to 1958, and 418 cases of 418 cases of hospitalized drug rash in 1959-1975 accounted for 7.9%. There were 23 cases of this type of drug eruption in 104 severe drug eruptions admitted from 1983 to 1992, accounting for 22%. Due to serious illness, if not rescued in time. Can lead to death.

The disease is characterized by a long incubation period, often between 20 and 20 days; the disease duration is long, usually at least one month or more. The whole course of disease development can be divided into four stages:

1 prodromal period, manifested as a transient rash, such as symmetrical erythema limited to the chest, abdomen or thigh, consciously itching, or with fever, this is a warning symptom, if you stop at this time may avoid the disease.

2 rash period, can slowly gradually develop from the face down, or begin to be an acute attack, and later with a rash or spread to the body quickly or slowly. When the rash episode is at a climax, the skin of the whole body is red and swollen, and the facial edema is remarkable. There is often a discharge of crusting, accompanied by chills and fever. Some patients may have visceral damage such as liver, kidney and heart. The total number of peripheral white blood cells is increased, generally between 15 × 109 ~ 20 × 109 / L (15000 ~ 20000 / mm3).

3 exfoliation period, which is a characteristic manifestation of this disease. The redness and sensation of the rash began to subside, and then it was scaly to large-scale desquamation. The scales could be covered with sheets and hands, such as wearing gloves, which were like wearing socks and repeatedly falling off for up to one to several months. Hair and nails often fall off at the same time. 4 During the recovery period, the scales of the fish are scaly or squamous, and then gradually disappear, and the skin returns to normal. Since the application of corticosteroids, the course of disease can be significantly shortened and the prognosis is greatly improved.

2. Short-term tincture dermatitis type: This is a mild toxic dermatitis seen in the short-term treatment of schistosomiasis in Japan in the 1950s. Its characteristics are:

1 The prevalence rate is high, generally between 30% and 40%, and some can be as high as 60% to 70%.

2 The incubation period is short, and both occur within 2 to 3 days after the start of treatment.

3 rash after the amount of tincture reached 0.3g.

4 more common in summer.

5 rashes are symmetrically distributed on the face, neck, back of the hand and fingers, occasionally in the chest and abdomen, resembling a scorpion, dense and not fused, mild inflammatory reaction, consciously itchy or burning sensation, and individual fever and other systemic symptoms.

6 The course of disease is self-limiting. Even if the drug is not stopped, the rash will mostly disappear within 3 to 5 days, accompanied by sputum-like desquamation.

7 re-treatment has occasional recurrence. No complications or sequelae were seen. Histochemical examination revealed no difference in rash between normal skin and normal skin (both about 2.5 g/dl). Histopathology resembles contact dermatitis and is non-specific.

3. papillary proliferative type

Mostly caused by long-term use of left iodine, bromine and so on. The incubation period is usually about one month. We have seen 2 cases, scattered on the basis of the whole body erythematous drug eruption, not very regular, significantly higher than the leather surface, about 3 ~ 4cm, the diameter of the papillary proliferative granuloma, the touch is quite solid, mainly Occurs in the trunk. Symptomatic treatment gradually subsided, the whole process is about 3 weeks.

4. Lupus-like reaction: Since the discovery of hydralazine in the early 1960s, it has been known that there are more than 50 drugs such as penicillin, procainamide, isoniazid, p-aminosalicylic acid, etc. Butalone, methylthiouracil, reserpine, metronidazole and oral contraceptives can cause such reactions. Clinically, the main manifestations are polyarticular pain, myalgia, polyserositis, pulmonary symptoms, fever, hepatosplenomegaly and lymphadenopathy, acral cyanosis and rash. The difference between this disease and true lupus erythematosus is caused by fever, tubular urine, hematuria, and azoazine. After the symptoms disappear, laboratory positives can persist for several months or even years.

5. Fungal disease type reaction: Due to the application of a large number of antibiotics, corticosteroids and immunosuppressive agents, it often causes environmental balance disturbance and dysbacteriosis in the body, and there is a fungal case reaction, which is manifested as Candida albicans or dermatophyte infection. Can have gastrointestinal, lung or other visceral infections, can affect multiple organs at the same time. It is not uncommon to find severe systemic fungal infections in the autopsy of immunosuppressants. It is worth noting that some patients with dermatophytosis, due to the application of the above drugs, the range of rickets lesions has become more extensive, and it is not easy to treat, even if cured, it is easy to relapse, causing difficulties in the prevention and treatment of rickets.

6. Corticosteroid type reaction: If the dose of hormone application is large, the time is long, often causing a variety of adverse reactions, and even lead to death. The main side effects it causes are:

1 secondary bacterial or fungal infection: the most common.

2 gastrointestinal tract: "steroid ulcers", even with blood, perforation.

3 central nervous system: euphoria, irritability, dizziness, headache, insomnia, etc.

4 cardiovascular system: palpitations, elevated blood pressure, thrombosis, heart rhythm and so on.

5 endocrine system: Kexing-like syndrome, osteoporosis, diabetes, cortical dysfunction and inhibition of growth and development of children.

6 skin: acne, hairy, telangiectasia, ecchymosis, skin atrophy, etc.

7 eyes: blurred vision, increased intraocular pressure, cataracts and glaucoma.

In recent years, with the emergence of new drugs, the concept of new drug rash was put forward in the 1980s, which made people have a better understanding of drug reactions. Almost all new drugs can cause a variety of different drug reactions. There are many types of -lactam antibiotics, and various cephalosporins and penicillins can cause rash or rash-like rash. Cytotoxic drugs can cause hair loss, urticaria, toxic green skin necrosis, photosensitivity dermatitis and stomatitis. There are many types of anti-rheumatic drugs, which can cause photosensitivity dermatitis, urticaria, purpura, maculopapular rash and stomatitis. Rifampicin, D-cetochlor and captopril can cause maculopapular rash, urticaria and erythematous pemphigus (deciduous). Psoriasis-like rash may occur after long-term application of -blockers such as Proud (alprenolol), oxylenol (opening, oxprenolol), propranolol (proproanolol), etc. Patients with excessive keratosis of the palmar palsy can also cause eczema, mossy rash and other types of hirsutism, and can also reverse male pattern hair loss and can also cause Stevens-Johnson syndrome.

diagnosis

Given the wide range of drug reactions, complex performance, and more specificity, it is sometimes difficult to determine the diagnosis. For the diagnosis of drug eruption, the clinical history is still the main basis, combined with rash performance and laboratory tests, and the possibility of other diseases is excluded, comprehensive analysis and judgment.

In laboratory tests, skin scratches and intradermal tests often detect the sensitivity of patients to penicillin or iodide, and have certain value in preventing anaphylactic shock, but they are of little significance in preventing drug eruptions. The in vitro test has been used for the detection of allergens by lymphocyte transformation test and radioallergosorbernt test (RAST), but it is only reliable for some drugs, and can be used under certain conditions, and has certain reference value.

Differential diagnosis

1. Urticaria-type drug eruption: The color of the wind group is bright red or dark red, and the duration of a single wind group often exceeds 24 hours. Itching, tingling, chest tightness, palpitation, suffocation and even shock. Caused by penicillin, salicylate, terpene, serum products.

2, scarlet fever type and measles type drug eruption: Scarlet fever type disease is a large number of dense needle tip scarlet spots, itching is obvious. Measles-type skin lesions are mainly composed of a large number of dark red miliary large macules, which are symmetrically distributed and are especially dense in the trunk. These two types of drug eruptions are mainly caused by sulfa drugs, penicillin, and antipyretic analgesics.

3, fixed drug eruption: characterized by repeated occurrence of erythema or blisters in the same site. Most of the patients are sulfa drugs, antipyretic analgesics and barbiturates.

4, polymorphic erythema type drug eruption: large round or oval erythema from soybeans to broad beans, symmetrically distributed in the trunk and limbs. Often caused by sulfa drugs, antipyretic analgesics, phenobarbital and so on.

5, eczema-type drug eruption: this type of drug eruption caused by sulfa drugs, penicillin, streptomycin, quinine.

6, purpura drug eruption: skin lesions mainly purple red bean bleeding hemorrhagic rash, occurs in both lower limbs, especially the calf. Often caused by phenacetin, sulfa drugs, barbiturates and quinine.

7, acne-type drug eruption: the same size of miliary red hair follicle papules, the appearance is similar to acne vulgaris, but no obvious blackheads. Mainly caused by cortisol, bromine, iodine, oral contraceptives.

8, exfoliative dermatitis-type drug eruption: sudden large-scale scarlet fever or measles-like erythema, quickly involved in the body. Extensive epidermal exfoliation began to appear after 1 to 2 weeks. Often caused by sulfa drugs, salicylates, phenobarbital and arsenic.

9, moss-type drug eruption: part of the skin lesions resemble lichen planus, mostly due to long-term or large doses of aflatra, chloroquine, quinidine, arsenic and gold agents.

10, the large sore epidermis release drug eruption: the skin lesions at the beginning of the dark red or purple red patches, the area has expanded dramatically, throughout the body within a few days. Mostly caused by sulfa drugs, antipyretic analgesics, penicillin, barbiturates and so on.

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