DRUG AND SKIN DISEASE

DRUG AND SKIN DISEASE

When it comes to teen substance abuse, it seems like we’re always playing catch up. Anytime a new drug hits the streets, its popularity soars, and we find ourselves fighting against it. At the same time, drugs that have been around for years sometimes rise sharply and unexpectedly in popularity. Why is that? There seems to be no rhyme or reason to either the increase, or decrease, in drug use among teens. Though certain trends have been discovered over the years, the cause of those trends seems a mystery. In the mind of a young person, the “risk” of using drugs has many dimensions. Not only do teens consider physical risk, but also emotional (acting inappropriately, or getting depressed), social/relational, and aspirational. Physical risks include addiction, while social risks include disappointing friends or family, and loosing friends. Aspirational risks include loosing a job, or getting in trouble with the law. All of these perceived risks - physical, emotional, social, and aspirational - are different with each drug, and contributing factors include things like anti-drug campaigns and parental involvement, including discussions about the risks of drug use.

Exanthema is an umbrella term for skin reactions that literally burst forth on the skin. Enanthematous reactions similarly occur on the mucous membranes. Typical characteristics of skin exanthemas include erythema (redness), or morbilliform (resembling measles) or maculopapular lesions. Macules are small, distinct, flat areas and papules are small, raised lesions. This is the most common type of drug-induced cutaneous reaction. The eruption often starts on the trunk; the extremities and intertriginous areas are often involved, but the face may be spared. The rash is usually bright red in colour and the skin may feel hot, burning or itchy. A widespread confluent erythematous rash (erythroderma), often associated with desquamation (exfoliative dermatitis), is one of the most severe patterns of cutaneous drug reaction. There may be systemic symptoms, such as fever, lymphadenopathy and anorexia. Possible complicationsinclude hypothermia, fluid and electrolyte loss, and infection. The main drugs implicated are sulfonamides, chloroquine, penicillin, phenytoin and isoniazid.

A fixed drug eruption is due to exogenous drugs or chemicals are the sole cause. It consists of erythematous round or oval lesions of a reddish, dusky purple or brown colour, sometimes featuring blisters, either bullae or vesicles. Initially, one lesion appears, although others may follow. The patient may complain of itching or burning in the affected area, but systemic involvement is usually absent. The eruption can appear within a day to a few weeks of ingesting the causative drug and can occur on any part of the skin or mucous membranes. The hands, feet, tongue, penis or perianal areas are most frequently affected. The site of the eruption is fixed, i.e. whenever the individual takes the causative drug the eruption occurs within hours at exactly the same site. Healing occurs over 7–10 days after the causative drug is stopped, although residual hyperpigmentation may be slow to resolve.  The pathogenesis of fixed drug eruption is not well understood. Familial cases have been reported and genetic susceptibility may have a role. There are many known causes, including food additives and pharmaceutical excipients. Sulfonamides, tetracyclines and NSAIDs are frequently implicated. Because phenolphthalein has been removed from most laxatives, it is much less oftenthe culprit than in past years. Where a fixed drug eruption is suspected, oral challenge to confirm the diagnosis is accepted and safe practice. Topical corticosteroids may help reduce the intensity of the reaction. 

Drug-induced urticaria is the second most common form of cutaneous drug reaction after exanthematous reactions. Urticaria is seen in association with anaphylaxis, angio-oedema or serum sickness. The clinical appearance of drug-induced urticaria is indistinguishable from that from other causes, but is often more severe and may be accompanied by hypotension, breathing difficulties, shock, and even death. Urticaria lesions, sometimes known as nettle rash or hives, present as raised, itchy, red blotches or weals that are pale in the centre and red around the outside. Drug-induced urticaria may occur after the first exposure to a drug or after many previously well-tolerated exposures. The onset is more rapid than with other drug eruptions; lesions usually developwithin 36 hours of initial drug exposure. Individual lesions rarely persist for more than 24 hours. On rechallenge, lesions may develop within minutes. Urticaria is characterised as acute when it lasts 6 weeks or less and chronic when it persists beyond this. Drugs are the cause of a minority of cases of chronic urticaria, and in this situation it may be difficult to establish the cause.  Acute anaphylaxis and anaphylactoid reactions typically present with angio-oedema, urticaria, dyspnoea and hypotension. Some drugs can cause or exacerbate acne. The term acneiform is applied to drug eruptions that resemble acne vulgaris. The lesions are papulopustular but comedones are usually absent.  Corticotropin (ACTH), corticosteroids, androgens (in females), oral contraceptives, haloperidol, isoniazid, phenytoin and lithium are among the most frequently implicated drugs. 

Psoriasiform eruptions are similar to idiopathic psoriasis and typically consist of erythematous plaques surmounted by large dry silvery scales. A number of drugs can induce psoriasis in patients with no previous history, and some can worsen pre-existing psoriasis, although many reports are anecdotal and causality is unknown. One definite trigger islithium, which can unveil psoriasis in susceptible patients or aggravate existing psoriasis.  The time course between initiation of the causative agent and exacerbation or formation of the eruption varies between drugs, from less than 1 month to more than 3 months.  Purpura describes small cutaneous extravasations of blood. It is an occasional feature of drug-induced skin eruptions, and in some cases it is the main characteristic. The main causes are thrombocytopenia or platelet dysfunction (drug-induced thrombocytopenia and platelet dysfunction are discussed in Chapter 12). However, a similar picture can be caused by damage to small blood vessels, either by immunological mechanisms or by changes in vascular permeability. Tests of haemostasis, including platelet function, are usually within normal limits. Drugs associated with non-thrombocytopenic purpura include aspirin, quinine, sulfonamides, atropine and penicillin.

The term vasculitis refers to inflammation of the blood vessels. The vasculitides comprise a diverse group of conditions that may be manifest mainly as a systemic or cutaneous disorder; both types may be due to drug therapy.  Several drugs can induce both systemic vasculitis with cutaneous  manifestations and cutaneous vasculitis without other organ involvement. About 10% of cases of acute cutaneous vasculitis are believed to be drug induced. The precise mechanism is unknown; however, it appears to be a type III hypersensitivity reaction with immune complex deposition in postcapillary blood vessels. Cutaneous vasculitis commonly presents with raised purpuric (purple) lesions on the legs, ranging in size from a pinpoint to several centimetres. Characteristically the margins are irregular or stellate. Other lesions include erythematous macules, haemorrhagic blisters and ulceration. Occasionally the buttocks, upper extremities, or even the trunk may be involved. Systemic symptoms, such as malaise, arthralgia and fever, are less common. Toxic epidermal necrolysis (TEN), or Lyell’s syndrome, is a medical emergency. The disorder is characterised by widespread full-thickness epidermal necrosis with involvement of more than 30% of the body surface area. Commonly, there is severe involvement of the mucous membranes (oropharynx, eyes and genitalia). The estimated incidence ranges from 0.4 to 1.2 per million population per year.  It has a high associated mortality approaching 40%. The main cause in adults is drugs. Patients with HIV infection, systemic lupus erythematosus and bone marrow transplant recipients seem to be predisposed to this disorder.  Elderly patients and those with extensive TEN have a worse prognosis. Drug-induced TEN is rare in children, in whom the diagnosis must be distinguished from staphylococcal ‘scalded skin syndrome’. 

Idiopathic pemphigus and bullous pemphigoid are autoimmune disorders. Idiopathic pemphigus typically features superficial flaccid blisters, although sometimes erythema, crusting and scaling are the major clinical signs. Idiopathic bullous pemphigoid is characterised by large tense blisters developing on an erythematous base. The fluid within is often haemorrhagic. A number of drugs, most of which contain a thiol (or sulphydryl) group in their molecular structure, such as penicillamine or captopril, have been implicated in causing a disorder closely resembling these idiopathic conditions.  Cicatricical pemphigoid is a rare variant in which mouth ulcers, eye problems and other complications may develop, with subsequent scarring. Linear IgA disease results from a deposition of IgA along the basement membrane zone. There are two somewhat different conditions, one affecting childhood and one adults. In the adult form the trunk is almost always affected but lesions can occur elsewhere. Photosensitivity denotes a reaction occurring when a photosensitizing agent in or on the skin reacts to normally harmless doses of ultraviolet or visible light. It may be due to topical or systemic drugs. Up to 8% of cutaneous drug reactions are photosensitivity eruptions.

Lichenoid drug eruptions (LDE) are so called because of their resemblance to idiopathic lichen planus. The first drugs reported to cause lichenoid skin reactions were arsenicals used in the treatment of syphilis. Several causative drugs are now known, although LDE are quite rare in comparison with other drug-induced skin reactions. The lesions can be described as small, shiny, purplish polygonal papules, sometimes with a network of white lines known as Wickham’s striae. They are usually itchy, but can be asymptomatic. The surrounding skin is completely normal. LDE can rarely affect the buccal mucosa; a characteristic white lace pattern may be present.  Idiopathic lichen planus has a predilection for the flexor aspects of the forearms and legs, whereas a lichenoid drug eruption typically has a more symmetric involvement of the trunk and extremities.  Many skin diseases are followed by changes in skin colour. In particular, after lichenoid eruptions and fixed drug eruptions there may be residual pigmentation. Drug-induced alteration in skin colour may result from increased (or more rarely decreased) melanin synthesis, increased lipofuscin synthesis, or cutaneous deposition of drug-related material. Sometimes the exact nature of the pigment is unknown. The pigmentation may be widespread or localized, and pigment deposits occasionally occur in internal organs.

Many drugs have been reported to cause hair loss .The human scalp has about 100 000 hairs, 100 of which are shed daily. Human hair follicles undergo three cyclical stages: the actively growing phase of anagen, which lasts about 3 years and features 80–90% of the scalp’s follicles; the brief involutionary phase of catagen; and the resting phase of telogen, which lasts about 3 months. The telogen phase culminates in the shedding of the hair shaft and at the same time new growth in the hair follicle begins.68–70 Hair follicles produce two types of hair according to the area of the body. Vellus hair is soft and colourless, covering the body surface apart from palms and soles. Terminal hair is the large, coarse, pigmented hair that occurs on the scalp, eyebrows, axillae etc. There are two patterns of unwanted increase in hair growth, both of which may be associated with drug administration. Hirsutism is an excessive growth of coarse hair with masculine characteristics in a female. This is a consequence of androgenic stimulation of hormonesensitive hair follicles. Drugs commonly responsible include testosterone, danazol, corticotropin, anabolic steroids and glucocorticoids. Patients with drug-induced hirsutism may also present with other dermatological signs of virilisation, such as acne.

A large number of drugs of different classes can be responsible for the development of nail changes.  Such changes usually involve several or all of the nails, and appear within a few weeks of drug administration. Nail problems can be asymptomatic or associated with pain and impaired digital function. They are usually reversible on drug discontinuation. Nail abnormalities include Beau’s lines (horizontal notches in the nail plate), brittle nails, onycholysis (separation of the nail plate from the nail bed), onychomadesis (separation of the nail plate from the matrix area, with progression to shedding) and paronychia (erythematous and tender nail folds). The nail can be considered to be homologous to hair and the same drugs frequently affect both tissues.  The pathogenesis of druginduced nail abnormalities is not well understood, but most cases are thought to involve a toxic effect of the drug on the nail epithelia. Other potential factors may be drug deposition in the nail plate, leading to nail discoloration and impaired digital perfusion, causing necrosis of the nail apparatus or damage to the nailbed blood vessels.

It’s hard to fight drug use among teens, but it can be done. Young people are more intelligent than we often give them credit for being. If we talk with them about specific drugs and their negative effects, it will go a long way towards winning the battle against teen drug use.