Dermatological emergencies

 

Dermatological emergencies

 

There are several conditions that can be classed as dermatological emergencies because of their severity and acute nature. Others can be classed as emergencies because it is essential to get a definitive diagnosis quickly so that correct treatment can be started immediately to prevent complications such as scarring.

 

 

Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis

 

These disorders represent a spectrum ranging in severity from relatively benign erythema multiforme to life-threatening toxic epidermal necrolysis. Erythema multiforme is usually secondary to infection (mainly herpes simplex) and presents with target lesions particularly on hands and feet. It can be more generalised, with mucosal involvement. Stevens-Johnson syndrome and toxic epidermal necrolysis are both, in most cases, caused by drugs, see Erythema multiforme - Drug eruptions. They are considered to be a continuum, with clinical features ranging from atypical targetoid lesions with blisters and severe mucosal involvement in Stevens-Johnson syndrome to widespread detachment of full-thickness epidermis, confluent erythema and skin tenderness in toxic epidermal necrolysis.

There is a mortality rate of up to 20% even with appropriate management in toxic epidermal necrolysis, but this was much higher several years ago. Most fatalities in patients with toxic epidermal necrolysis are the result of sepsis. If Stevens-Johnson syndrome or toxic epidermal necrolysis is suspected then hospital admission is essential. Patients with toxic epidermal necrolysis should be admitted to a burns unit. All drugs should be stopped.

Treatment consists of: fluid and electrolyte replacement; maintenance of body temperature; adequate pain relief; early treatment of infection; debridement where needed; treatment of mucosal surfaces, especially the eye, where there is a 30% long-term morbidity. The role of oral corticosteroids is controversial but if they are to be given they need to be started early, in high doses and should be given for short periods of time, see Erythema multiforme - Drug eruptions . Cyclosporin has been reported in some recent articles to be effective.

Drug eruption: descriptions, causes and management

 

These are typically maculopapular or morbilliform rashes that are the most common of all drug rashes. Small erythematous macules or barely raised papules begin on the trunk and may coalesce. Slight pruritus is typical. The drugs most commonly associated with a drug exanthem are ampicillin, amoxycillin, cotrimoxazole, carbamazepine, cefaclor and gold. Management involves withdrawal of the drug and the use of simple emollients. Occasionally, moderately potent topical corticosteroids,  may be needed to relieve pruritus.

This is the second most common pattern of drug eruption and is manifested by pruritic erythematous wheals. This may be associated with angioedema of the lips or eyelids. The most common causes of drug-induced urticaria are antibiotics, particularly penicillins, captopril and other ACE inhibitors, NSAIDs including aspirin, and quinine. Treatment involves immediate cessation of the causative agent, and the use of an antihistamine. For more persistent cases or if there is significant angioedema

prednisolone 0.5 to 1mg/kg orally, daily for 7 days may be warranted.

 

This is rare and is manifest by a pruritic erythroderma, characterised by generalised erythema and scale. It may begin as a maculopapular erythema that progresses, generalises, persists and worsens. This can be associated with malaise, fever and lymphadenopathy.

Drugs causing erythroderma include allopurinol, antimalarials, carbamazepine, penicillins and sulfonamides. Erythroderma due to drugs needs to be managed by the immediate withdrawal of the offending agent and institution of therapy as for erythroderma of any other cause, see Emergencies: Exfoliate dermatitis (erythroderma). These patients require adequate nursing care to ensure that heat, fluid and protein loss through the skin is minimised. Systemic involvement, most commonly manifest by hepatitis, may further complicate management. Any suspicious drugs should be withdrawn. Pruritus and cutaneous inflammation may be reduced with

Emollients OR moderately potent topical corticosteroids.

 

Drugs that photosensitise (NSAIDs, ciprofloxacin, nalidixic acid, phenothiazines, tetracyclines, griseofulvin, amiodarone, sulfonamides and thiazides) cause the skin to become abnormally sensitive to light, usually solar radiation. This can occur with either topically applied medications, eg sunscreen formulations, or systemically ingested medications. These reactions can be either phototoxic or photoallergic, phototoxic reactions being far more common.

Phototoxic reactions are dependent on both the dose of radiation and the dose of medication. They can therefore occur at the time of commencement of therapy, or at a later date due to an increase in dose of medication or increase in sun exposure, as happens seasonally or when travelling to sunnier climes. Photoallergic reactions indicate an immunological reaction involving the skin and drug. They are not dose-related, and require a latent period of 24 to 48 hours for the sensitisation to occur.

The eruption will be prominent on the face (sparing deep creases, the area under the point of the chin and behind the ears), the dorsum of the hands and the ‘V’ of the neck. With continued exposure, the eruption can eventually extend to involve sun-protected areas as well as the sun-exposed sites.

Some mild photosensitive eruptions, eg due to thiazides, are very common and may not necessitate the cessation of the drug. It is, however, important to stress increased solar protection, ie sun avoidance, adequate clothing including hats, and a broad-spectrum sunscreen,. The photosensitivity to some agents such as thiazides can take many months to resolve and consequently prolonged photoprotection may be necessary.

Local irritation may be controlled with emollients (see Control of xerosis) and moderately potent topical corticosteroids.

Erythema multiforme is characterised by ‘target’ lesions involving the skin with occasional involvement of the mucosal surfaces, see Erythema multiforme - Mouth ulcers. Only 10% of cases are due to drugs. On the other hand, the severe form, Stevens-Johnson syndrome, is usually a drug reaction. It is marked by extensive and sometimes exclusive involvement of mucosal surfaces (oral, ocular, genital and others) with cutaneous target lesions variably present, and this is very likely the result of a drug reaction.

Drugs associated with erythema multiforme and Stevens-Johnson syndrome include allopurinol, carbamazepine, phenytoin, gold, NSAIDs, sulfonamides and tetracyclines. Stevens-Johnson syndrome is a serious and occasionally life threatening condition, see Emergencies. The drug must be stopped and expert care given to the affected mucous membranes. If the disease is recognised early in its course (within the first 72 hours), use

prednisolone 0.5 to 1mg/kg orally, daily until lesions cease cropping then reduce the dose and cease over 1 week.

 

Toxic epidermal necrolysis is a rare and potentially fatal condition that is usually precipitated by drugs. The rash often begins with a morbilliform eruption. This rapidly progresses to result in skin that is easily detached, with large sheets separating at the dermoepidermal junction. This resembles a second-degree burn in a patient who is acutely ill, often with a high fever. The mucosa is often extensively involved, especially the eyes. Here it can produce significant scarring sequelae in those patients who survive. Toxic epidermal necrolysis is a medical emergency, Previously, mortality rates were as high as 60% but have steadily declined to around 20% because of improved medical and nursing care.

Drugs causing toxic epidermal necrolysis include allopurinol, ampicillin, amoxycillin, carbamazepine, phenytoin, lamotrigine, nevirapine, barbiturates, sulfonamides, cephalosporins and NSAIDs.

Patients need intensive care or burns unit care to avoid the systemic complications of renal failure and electrolyte imbalance, as well as reverse barrier nursing to reduce the risk of sepsis. Specific treatment of this condition is still controversial; some patients have apparently responded to agents such as cyclosporin and prednisolone. Urgent referral to specialist care is essential.

Drug-induced vasculitis may not only cause the typical ‘palpable purpura’ but may also involve internal organs, including the kidneys, liver and heart. Drugs associated with vasculitis include ACE inhibitors, NSAIDs, sulfonamides and thiazide diuretics. Assessment of a patient with a drug-induced vasculitis requires investigations to exclude other causes of the vasculitis and to assess any systemic involvement, see Management of cutaneous vasculitis.

These eruptions are so-called because they resemble lichen planus. There are clinical differences between idiopathic lichen planus and drug-induced lichenoid eruptions. Drug-induced cases have a tendency to be more severe and generalised, may show a photoexacerbation of lesions, and may be associated with some dermatitis-like areas and less mucosal involvement. These typically begin weeks or months after commencement of the drug and will often take several weeks to resolve after drug cessation.

Drugs commonly causing lichenoid eruptions include beta-blockers, ACE inhibitors, antimalarials, frusemide, thiazides, chlorpropamide, methyldopa, gold, phenothiazines and quinidine. Treatment of a lichenoid eruption involves cessation of the drug and photoprotection, if relevant, together with

emollients AND a moderately potent to potent topical corticosteroid.

 

Fixed drug eruptions characteristically recur in the same site(s) with each administration of the causative agent. They are seen particularly with drugs that are ingested episodically, such as those for night cramps, dysmenorrhoea or constipation. The lesion is typically a single, well-demarcated, erythematous plaque, a few millimetres to many centimetres in diameter, and may be surmounted by a bulla. It develops 30 minutes to 8 hours after administration of the drug and is typically associated with burning rather than itch. If the drug is continued, multiple lesions can develop. Common sites affected are the face, hands, feet, genitalia (especially the glans penis) and the perianal area. When the drug is ceased the lesion resolves, leaving a well-demarcated patch of macular hyperpigmentation.

Common culprits in fixed drug eruptions include tetracyclines, sulfonamides, NSAIDs, paracetamol, phenolphthalein and barbiturates. Management involves taking a full and exhaustive history of drug ingestion, remembering that causative agents are often not considered to be drugs by the patient. The drug should be stopped.

For symptomatic relief, use

a moderately potent to potent topical corticosteroid.

 

If the reaction is severe or there is extensive mucosal involvement, use

prednisolone 0.5 to 1mg/kg orally, each morning for 3 to 7 days.

 

To confirm a clinically suspicious drug, a small dose of the agent could be taken as a rechallenge. This would be ill advised if the previous reaction had been severe, extensive or with significant mucosal involvement.

This severe reaction is manifest by fever, skin rash and hepatitis. It typically begins 2 to 3 weeks after initiation of therapy and may continue or worsen for weeks after the drug is ceased. Other signs include lymphadenopathy, leukocytosis with atypical lymphocytes, and nephritis. The skin rash is predominantly morbilliform, but erythroderma and toxic epidermal necrolysis have been reported. The outcome is variable, but the syndrome may be fatal, usually due to liver involvement.

Expert medical and nursing care is needed to assist recovery after the drug is stopped. Systemic corticosteroids are used to hasten resolution. There is a high risk of cross-reaction between aromatic anticonvulsants (phenytoin, carbamazepine, phenobarbitone, see Cross reactivity), which means that other anticonvulsants need consideration. Other drugs can produce a similar hypersensitivity syndrome.

Many drugs have been implicated in either precipitating or aggravating a variety of cutaneous diseases. The worsening of psoriasis and acne vulgaris by lithium is the best recognised example, but the exacerbation of psoriasis has also been reported with beta-blockers and antimalarials. If a rash is believed to have been responsible for worsening or indeed precipitating a dermatosis, consideration should be given to ceasing the drug in question. Assessment of the progression of the rash after cessation of the drug is then required. Rash aggravation by a medication may not necessarily preclude the use of this medication at a future time by the same patient. The withdrawal of a drug may also be responsible for the aggravation of a rash, eg the worsening of psoriasis on withdrawal of oral corticosteroids.

 

Staphylococcal scalded skin syndrome

 

Children and neonates are most susceptible. They present with irritability and raised temperature, along with skin tenderness and a scarlatiniform eruption, leading to superficial crusting initially in the flexures and around body orifices and then becoming generalised. Treatment is with supportive measures and

di/flucloxacillin 2g (children: 25 to 50mg/kg up to 2g) orally, 6-hourly.

 

Corticosteroids are contraindicated.

 Vasculitis

 

Vasculitis presents as a palpable purpura, predominantly on the legs, with severe cases leading to ischaemia and necrosis. It is important to exclude systemic involvement by means of appropriate investigations. Treatment is supportive but, if severe, oral corticosteroids can be given. Cutaneous vasculitis is discussed in detail elsewhere.

The classical clinical lesion of vasculitis is palpable purpura, most commonly of the legs. Urticaria, erythematous swellings, vesicles, pustules, bullae, erythematous macules, papules and plaques can, however, be seen in the cutaneous eruption. Vasculitis is usually defined histologically as a process that involves the destruction of blood vessels, most often with cellular infiltrate of the vessel walls, proliferation of the intima, fibrinoid change in the vessel walls and narrowing or occlusion of the vessel lumen. Clinical manifestations vary with the site, size and depth of the vessel involved.

Cutaneous vasculitis may be confined to the skin but may be a feature of a more systemic process with involvement of organs including joints, eyes, kidney, heart, gastrointestinal tract, lungs and central nervous system. The aetiology is most often attributed to deposition of immune complexes in the vessel walls with antigen excess but can be due to nonimmunological mechanisms in which inflammation destroys the vessel wall. The clinical appearance will be critically affected by coexistent infection, drugs being taken, circulatory function, platelet numbers and function, heat, cold and local pressure.

Diagnosis should be confirmed by biopsy with immunofluorescence. Diseases to be excluded include Sweets syndrome, erythema nodosum, urticaria and pyoderma gangrenosum.

Drugs are frequent causes of cutaneous vasculitis. Sometimes the addition of a new drug to a variety of other drugs may tip the balance in favour of immune complex deposition although the new drug is not the primary cause, eg addition of a nonsteroidal anti-inflammatory drug (NSAID). Therefore, more than one drug may need to be stopped. Antibiotics are most frequently implicated. Other inflammatory factors induced by infection may predispose to development of vasculitis and every effort should be made to avoid using the suspect drug again. Although drugs are a frequent cause of vasculitis, vasculitis is a relatively uncommon manifestation of cutaneous adverse reactions to drugs. Many drugs have been reported as causes but those most commonly implicated are allopurinol, aminosalicylic acid, amiodarone, ampicillin, captopril, cimetidine, erythromycin, fluoroquinolones, frusemide, griseofulvin, hydralazine, iodides, methotrexate, penicillin, phenacetin, phenylbutazone, propylthiouracil, quinidine, sulfonamides, tetracyclines, thiazides and warfarin. Other exogenous chemical factors include food additives, radiocontrast media and vaccination.

Streptococcal infections, tuberculosis and leprosy can cause cutaneous vasculitis. The classical association is that of poststreptococcal involvement in Henoch-Schönlein purpura. Viral causes include hepatitis B, hepatitis C and human immunodeficiency virus.

Cutaneous vasculitis may be a manifestation of an associated disease such as rheumatoid arthritis, Sjögren’s syndrome, systemic lupus erythematosus (SLE), hypergammaglobulinaemia, cryoglobulinaemia and associated connective tissue disease, as well as hepatitis B and C. Cutaneous vasculitis has also been reported in association with lymphoma, leukemia, Hodgkin’s disease and myelodysplasias.

As cutaneous involvement is most often due to damage to capillaries and venules, small vessel involvement in other organs should be excluded. Assessing organ involvement should include a search for lymphadenopathy, hepatosplenomegaly, arthritis, conjunctivitis, episcleritis, uveitis and involvement of renal, gastrointestinal, upper and lower respiratory, and central nervous systems. A reasonable diagnostic screen includes full blood count, erythrocyte sedimentation rate, C-reactive protein, microurine, renal and liver function tests, total complement levels and antinuclear factor. If indicated, rheumatoid factor, cryoglobulins, immunoglobulins and C4 and C2 levels should be assessed. By definition, the diagnosis will have been confirmed by biopsy with immunofluorescence.

Patients should be treated with bed rest and will frequently need hospitalisation. Blistering, weeping or ulcerated areas should be treated with wet dressings, see Specific treatments of dermatitis, until the disease is stable. Painful lesions may require relief with paracetamol and codeine unless they are contraindicated. When the condition has stabilised, ulcers may be treated with an occlusive hydrocolloid dressing. Below-knee compression stockings, may hasten healing of chronic ulcerative lesions and allow for early ambulation.

Systemic therapy may not be necessary after the above measures have been followed, as there is often a tendency for gradual remission. It is difficult to generalise, as individual entities may require specific therapies. If a clear removable cause has not been established and the distribution and number of lesions continues to extend, or if there is involvement of other organ systems such as the kidney, lung or joints then the usual treatment is with systemic corticosteroids. Use

prednisolone 1mg/kg orally, daily.

 

Tapered reduction of the prednisolone can be commenced once new lesions cease to appear. If control is not achieved with corticosteroids then additional corticosteroid-sparing agents such as azathioprine or cyclophosphamide may be added. Other drugs used in cutaneous vasculitis, depending on the course and severity of the disease, include

dapsone 50 to 100mg OR colchicine 1.5 to 3mg OR hydroxychloroquine 200mg orally, daily.

 

These drugs are effective against the neutrophilic forms of cutaneous vasculitis. Colchicine inhibits neutrophil chemotaxis.

If cutaneous involvement or arthralgia are the only features and the disease is stable, use

an NSAID .

 

Less frequently used options include oxpentifylline or a combination of aspirin and dipyridamole where there is an element of small vessel occlusion. Antihistamines, eg cetirizine, may have a place in early symptomatic treatment where itch is prominent or where there is an urticarial component.

This cutaneous necrotising vasculitis is diagnosed on the basis of immunofluorescent findings of IgA antibodies deposited in and around cutaneous blood vessels. Similar appearances are evident in kidney biopsies. The disease was formerly described predominantly in children following upper respiratory tract infection and associated with joint, gastrointestinal tract and renal involvement as well as skin rash. However, the diagnosis is frequently made in adults solely on the basis of the immunofluorescence findings and compatible skin lesions. Management is similar to that described for other forms of cutaneous vasculitis with systemic involvement and also includes adequate follow up to detect sequelae.

Livedo is common in minor forms in otherwise normal women. The finding of an accentuated, broad, net-like pattern of cyanotic discolouration is seen particularly on the skin of extremities and is associated with small to medium vessel arterial disease or where sluggish skin blood flow is caused by increased viscosity, eg in antiphospholipid antibody (APL) syndrome. Livedo may be associated with cerebral ischaemic episodes in APL syndrome. When associated with nodular vasculitis it is known as cutaneous polyarteritis nodosa. Livedo that does not disappear with vasodilatation due to high ambient temperature, or is patchy or broken, is more likely to be of pathological significance.

This is a form of nodular vasculitis confined to the skin where erythematous nodules, usually on the lower legs, are associated with livedo reticularis. This form of polyarteritis nodosa is not life threatening but may have significant morbidity. Treatment is with bed rest, NSAIDs and exclusion of precipitating factors.

When urticaria-like lesions persist for 24 to 48 hours and particularly if they fade with bruising, the possibility of urticarial vasculitis would be entertained. There is usually an association with low levels of complement and biopsy confirms vasculitis. Management is by excluding associated conditions such as SLE or possible drug causes and exclusion of involvement of other organs such as the kidney, joints and lungs. If systemic therapy is indicated and the patient is unresponsive to antihistamines, use

prednisolone 25 to 50mg orally, daily for 1 week then taper the dose over 2 to 3 weeks.

 

If there is no response, try indomethacin, colchicine, dapsone or hydroxychloroquine as shown in When should systemic therapy be used? Plasmapheresis has been used for severe, refractory disease.

 

Meningococcal septicaemia

 

A preceding viral-like illness is followed by petechial lesions plus transient urticarial, macular or papular lesions. The petechiae have a ‘smudged’ appearance and are raised with pale greyish centres. There is associated fever and there may be signs of meningitis. For further information on management, see the chapter on Neisseria meningitidis.

Use

benzylpenicillin (child: 60 mg/kg up to) 1.8 to 2.4 g IV, 4-hourly for 5 to 7 days.

 

For patients hypersensitive to penicillin (excluding immediate hypersensitivity), use

1	cefotaxime (child: 50 mg/kg up to) 2 g IV, 6-hourly for 5 to 7 days
	OR
1	ceftriaxone (child: 100 mg/kg up to) 4 g IV, daily OR (child: 50 mg/kg up to) 2 g IV, 12-hourly for 5 to 7 days

Dermatological emergencies: drug eruptions

There are many different presentations including Stevens-Johnson syndrome/toxic epidermal necrolysis, vasculitis, exfoliative dermatitis, and urticarial, maculopapular, pustular and lichenoid eruptions. A drug history should always be obtained with any skin eruption and suspected offending drug or drugs ceased. Drug eruptions are discussed elsewhere.

Primary herpetic gingivostomatitis

This is a disease of children and young adults with a peak incidence occurring between ages 1 and 5 years. It may be mild or severe with high fever, sore throat and painful vesicles and ulcerative erosions on the buccal mucosa, tongue and lips. Urgent identification of herpes simplex virus by viral swab is needed. In cases of severe infection, antiviral therapy is recommended. Use

famciclovir 250mg (children: 6mg/kg up to 250mg) OR valaciclovir 1g (children: 25mg/kg up to 1g) orally, 8-hourly OR aciclovir 200mg (children: 5mg/kg up to 200mg) orally, 5 times daily (every 4 waking hours)

 

If unable to swallow, use

aciclovir 5mg/kg (for all ages) IV, 8-hourly.

 

Eczema herpeticum

 

This is defined as dermatitis with secondary herpes simplex virus infection and should be considered as a possible cause of any acute flare of dermatitis. The signs are grouped vesicles and erosions on a weeping dermatitis, with associated fever and malaise. Skin tenderness is more common than itching. A viral swab is needed for diagnosis. Hospital admission may sometimes be required. Staphylococcus aureus commonly colonises but diffuse redness and crusting suggest bacterial infection (see Impetigo). This condition is more often seen in children than adults. Treatment is with antiviral drugs

1	valaciclovir 500 mg orally, 12-hourly until healed
	OR
2	famciclovir 250 mg orally, 12-hourly until healed
	OR
3	aciclovir (child: 5 mg/kg up to) 200 mg orally, 5 times daily until healed.

 

For more severe disease, use

aciclovir (for all ages) 5 mg/kg IV, 8-hourly initially, THEN an oral regimen as above.

 

Initial topical therapy should include wet dressings or compresses with potassium permanganate or aluminium acetate solution. Topical corticosteroids should be avoided until the infection is under control.

 

Generalised pustular psoriasis

 

This disorder presents as a sudden generalised eruption of small pustules on erythematous skin with associated fever and systemic symptoms, see Erythrodermic psoriasis. It is potentially fatal and needs hospital admission. Oral retinoids are the drugs of choice and lead to rapid improvement

acitretin 10 to 75mg orally, daily.

 

Note:

Acitretin is teratogenic and pregnancy should be avoided during its use and for 2 years following cessation of therapy. In Australia, state laws require prescription of acitretin by a dermatologist.

 

Alternatively, use

methotrexate 0.2 to 0.4mg/kg (average 15mg) orally per week in 3 divided doses (eg 3 doses of 5mg, spaced 12 hours apart).

 

Cutaneous drug reactions may mimic this condition and if suspected should be stopped. Oral corticosteroids are rarely used because of rebound flare with cessation.

 Weeping dermatoses

 

These may be due to an acute contact dermatitis, infected dermatitis or pompholyx. Severe pompholyx on hands and feet can be very distressing and incapacitating. On the feet it needs to be differentiated from an acute blistering tinea. The treatment of pompholyx is also discussed in Specific treatments for dermatitis.

Initial topical therapy includes soaks or compresses with potassium permanganate or aluminium acetate solution, see Pompholyx - Specific treatments for dermatitis. If infection is present, an antistaphylococcal antibiotic is needed, see Antibiotic therapy - General treatment of dermatitis.

When improving, topical corticosteroids can be started, using

a potent topical corticosteroid, applied twice daily.

 

If severe or unresponsive to topical corticosteroids, use

prednisolone 30 to 50mg orally, daily for several days then taper dose over 2 weeks.

 Exfoliative dermatitis (erythroderma)

 

These terms are applied to any inflammatory skin disease that affects more than 90% of the body surface. The cause is not found in 10% of patients. The most common causes are dermatitis, psoriasis, drugs, lymphoma, pityriasis rubra pilaris and Norwegian (crusted) scabies. There are profound metabolic disturbances which mean that rapid diagnosis and management is needed. These disturbances include hypothermia, fluid loss, protein and electrolyte imbalance and haemodynamic changes. Treatment in hospital is needed to manage the metabolic and haemodynamic changes. Any suspected drug should be withdrawn. Treatment is directed at the underlying cause but oral corticosteroids are effective for cases due to dermatitis or drugs.