Kevin Bryan Uy Lo, MD

A 66-year-old man presented with burning pain and erythema over the left axilla, and pustules that had ruptured and crusted over. The rash also involved the right axilla, trunk, abdomen, and face.

He said the symptoms had developed 3 days after starting to use ciprofloxacin eye drops for eye redness and purulent discharge that had been diagnosed as bacterial conjunctivitis. He was taking no other new medications. He was afebrile.

He was admitted to the hospital. Examination revealed a desquamating rash over the left axilla (Figure 1), with multiple ruptured and crusted-over pustules over the right axilla, chest, and abdomen (Figure 2). No mucosal lesions were noted. Laboratory testing showed a white blood cell count of 9.24 × 10⁹/L (reference range 4.5–11.0) with 7.8% eosinophils (0%–4%). Blood cultures were negative.

Skin biopsy study on the day after admission showed diffuse spongiosis with scattered eosinophils and a pustule beneath the stratum corneum. These findings, along with the timing and presentation of symptoms, confirmed suspicion of acute generalized exanthematous pustulosis related to the use of the eye drops.

The ciprofloxacin drops were stopped. The skin lesions were treated with emollients, topical steroids, and topical mupirocin. Improvement was noted 3 days into the hospitalization, as the lesions started to crust over and dry up and no new lesions were forming. The conjunctivitis improved with topical bacitracin ointment and prednisolone drops.

ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS

The differential diagnosis of drug-related acute generalized exanthematous pustulosis includes Stevens-Johnson syndrome, pustular psoriasis, folliculitis, and varicella infection. The characteristic features of the rash and lesions and the temporal relationship between the start of ciprofloxacin eye drops and the development of symptoms, combined with rapid resolution of symptoms within days after discontinuing the drops, accompanied by skin biopsy study showing diffuse spongiosis with scattered eosinophils and a subcorneal pustule, confirmed the diagnosis of AGEP.

Key features of AGEP include numerous small, sterile, nonfollicular pustules on an erythematous background with associated fever and sometimes neutrophilia and eosinophilia.¹ It usually begins on the face or in the intertriginous areas and then spreads to the trunk and lower limbs with rare mucosal involvement.¹ It can be associated with viral infections, but most reported cases are related to drug reactions.²

Our patient’s case was unusual because AGEP triggered by topical medications is rarely reported, especially with ophthalmic medications.³ Drugs most commonly implicated are antibiotics including penicillins, sulfonamides, and quinolones, but other drugs such as terbinafine, diltiazem, and hydroxychloroquine have also been associated.²

AGEP may present with extensive skin desquamation, as in our patient, sometimes with bullae formation and skin sloughing manifesting as AGEP with overlapping toxic epidermal necrolysis.⁴

Diagnosis entails a careful review of medications, attention to lesion morphology, compatible disease course, and a high index of suspicion. Treatment is supportive and consists of stopping the offending agent, wound care, and antipyretics. Evidence for the use of steroids is weak.⁵

TAKE-HOME POINTS

AGEP should be considered in sudden-onset pustular desquamating erythematous rash related to use of a new medication. It is important to be aware that topical and ophthalmic medications are possible triggers. A thorough medication review should be done. Antibiotics are the most commonly implicated medications. An alternative medication should be tried. Treatment is supportive, as the condition is usually self-limiting once the offending medication is discontinued. Rarely, extensive desquamation and bullae formation may occur, which may be a manifestation of overlap features with toxic epidermal necrolysis.

A 66-year-old man presented with burning pain and erythema over the left axilla, and pustules that had ruptured and crusted over. The rash also involved the right axilla, trunk, abdomen, and face.

He said the symptoms had developed 3 days after starting to use ciprofloxacin eye drops for eye redness and purulent discharge that had been diagnosed as bacterial conjunctivitis. He was taking no other new medications. He was afebrile.

He was admitted to the hospital. Examination revealed a desquamating rash over the left axilla (Figure 1), with multiple ruptured and crusted-over pustules over the right axilla, chest, and abdomen (Figure 2). No mucosal lesions were noted. Laboratory testing showed a white blood cell count of 9.24 × 10⁹/L (reference range 4.5–11.0) with 7.8% eosinophils (0%–4%). Blood cultures were negative.

Skin biopsy study on the day after admission showed diffuse spongiosis with scattered eosinophils and a pustule beneath the stratum corneum. These findings, along with the timing and presentation of symptoms, confirmed suspicion of acute generalized exanthematous pustulosis related to the use of the eye drops.

The ciprofloxacin drops were stopped. The skin lesions were treated with emollients, topical steroids, and topical mupirocin. Improvement was noted 3 days into the hospitalization, as the lesions started to crust over and dry up and no new lesions were forming. The conjunctivitis improved with topical bacitracin ointment and prednisolone drops.

ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS

The differential diagnosis of drug-related acute generalized exanthematous pustulosis includes Stevens-Johnson syndrome, pustular psoriasis, folliculitis, and varicella infection. The characteristic features of the rash and lesions and the temporal relationship between the start of ciprofloxacin eye drops and the development of symptoms, combined with rapid resolution of symptoms within days after discontinuing the drops, accompanied by skin biopsy study showing diffuse spongiosis with scattered eosinophils and a subcorneal pustule, confirmed the diagnosis of AGEP.

Key features of AGEP include numerous small, sterile, nonfollicular pustules on an erythematous background with associated fever and sometimes neutrophilia and eosinophilia.¹ It usually begins on the face or in the intertriginous areas and then spreads to the trunk and lower limbs with rare mucosal involvement.¹ It can be associated with viral infections, but most reported cases are related to drug reactions.²

Our patient’s case was unusual because AGEP triggered by topical medications is rarely reported, especially with ophthalmic medications.³ Drugs most commonly implicated are antibiotics including penicillins, sulfonamides, and quinolones, but other drugs such as terbinafine, diltiazem, and hydroxychloroquine have also been associated.²

AGEP may present with extensive skin desquamation, as in our patient, sometimes with bullae formation and skin sloughing manifesting as AGEP with overlapping toxic epidermal necrolysis.⁴

Diagnosis entails a careful review of medications, attention to lesion morphology, compatible disease course, and a high index of suspicion. Treatment is supportive and consists of stopping the offending agent, wound care, and antipyretics. Evidence for the use of steroids is weak.⁵

TAKE-HOME POINTS

AGEP should be considered in sudden-onset pustular desquamating erythematous rash related to use of a new medication. It is important to be aware that topical and ophthalmic medications are possible triggers. A thorough medication review should be done. Antibiotics are the most commonly implicated medications. An alternative medication should be tried. Treatment is supportive, as the condition is usually self-limiting once the offending medication is discontinued. Rarely, extensive desquamation and bullae formation may occur, which may be a manifestation of overlap features with toxic epidermal necrolysis.

A 66-year-old man presented with burning pain and erythema over the left axilla, and pustules that had ruptured and crusted over. The rash also involved the right axilla, trunk, abdomen, and face.

He said the symptoms had developed 3 days after starting to use ciprofloxacin eye drops for eye redness and purulent discharge that had been diagnosed as bacterial conjunctivitis. He was taking no other new medications. He was afebrile.

He was admitted to the hospital. Examination revealed a desquamating rash over the left axilla (Figure 1), with multiple ruptured and crusted-over pustules over the right axilla, chest, and abdomen (Figure 2). No mucosal lesions were noted. Laboratory testing showed a white blood cell count of 9.24 × 10⁹/L (reference range 4.5–11.0) with 7.8% eosinophils (0%–4%). Blood cultures were negative.

Skin biopsy study on the day after admission showed diffuse spongiosis with scattered eosinophils and a pustule beneath the stratum corneum. These findings, along with the timing and presentation of symptoms, confirmed suspicion of acute generalized exanthematous pustulosis related to the use of the eye drops.

The ciprofloxacin drops were stopped. The skin lesions were treated with emollients, topical steroids, and topical mupirocin. Improvement was noted 3 days into the hospitalization, as the lesions started to crust over and dry up and no new lesions were forming. The conjunctivitis improved with topical bacitracin ointment and prednisolone drops.

ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS

The differential diagnosis of drug-related acute generalized exanthematous pustulosis includes Stevens-Johnson syndrome, pustular psoriasis, folliculitis, and varicella infection. The characteristic features of the rash and lesions and the temporal relationship between the start of ciprofloxacin eye drops and the development of symptoms, combined with rapid resolution of symptoms within days after discontinuing the drops, accompanied by skin biopsy study showing diffuse spongiosis with scattered eosinophils and a subcorneal pustule, confirmed the diagnosis of AGEP.

Key features of AGEP include numerous small, sterile, nonfollicular pustules on an erythematous background with associated fever and sometimes neutrophilia and eosinophilia.¹ It usually begins on the face or in the intertriginous areas and then spreads to the trunk and lower limbs with rare mucosal involvement.¹ It can be associated with viral infections, but most reported cases are related to drug reactions.²

Our patient’s case was unusual because AGEP triggered by topical medications is rarely reported, especially with ophthalmic medications.³ Drugs most commonly implicated are antibiotics including penicillins, sulfonamides, and quinolones, but other drugs such as terbinafine, diltiazem, and hydroxychloroquine have also been associated.²

AGEP may present with extensive skin desquamation, as in our patient, sometimes with bullae formation and skin sloughing manifesting as AGEP with overlapping toxic epidermal necrolysis.⁴

Diagnosis entails a careful review of medications, attention to lesion morphology, compatible disease course, and a high index of suspicion. Treatment is supportive and consists of stopping the offending agent, wound care, and antipyretics. Evidence for the use of steroids is weak.⁵

TAKE-HOME POINTS

AGEP should be considered in sudden-onset pustular desquamating erythematous rash related to use of a new medication. It is important to be aware that topical and ophthalmic medications are possible triggers. A thorough medication review should be done. Antibiotics are the most commonly implicated medications. An alternative medication should be tried. Treatment is supportive, as the condition is usually self-limiting once the offending medication is discontinued. Rarely, extensive desquamation and bullae formation may occur, which may be a manifestation of overlap features with toxic epidermal necrolysis.

A 96-year-old woman with hypertension, diabetes,    and dementia was found unresponsive in her nursing home and was transferred to the hospital.

At presentation to the hospital, her blood pressure was 76/43 mm Hg, heart rate 42 beats per minute, rectal temperature 31.6°C (88.8°F), and blood glucose 36 mg/dL.

The initial electrocardiogram (ECG) (Figure 1) showed sinus bradycardia with first-degree atrioventricular block and a PR interval of 704 ms. The QRS interval was mildly increased, and the corrected QT interval was mildly prolonged at 476 ms. There was also evidence of probable small Osborn waves in leads II and V₅, and leads aVF and aVL seemed reversed, as was confirmed in successive ECGs.

The patient was resuscitated with intravenous fluids and glucose and was rewarmed. Repeat ECG 3 hours later (Figure 2) revealed sinus bradycardia with first-degree atrioventricular block and a PR interval of 216 ms with a rate of 52. This time the leads were confirmed in correct position, with aVF showing negative QRS deflection. Q waves were also noted in leads III and aVF, as in previous ECGs, and suggested an old inferior wall infarction. This was not seen on the first ECG because of probable lead reversal, and the suspected Osborn waves were also less prominent in V₅ and absent in lead II. The corrected QT interval was now 465 ms, and her body temperature at this time was 32.8°C (91.0°F).

Causes of secondary hypothermia were sought. Blood and urine cultures were negative. Computed tomography of the head showed no acute intracranial abnormalities. Tests for adrenal insufficiency and hypothyroidism were negative.

HYPOTHERMIA AND THE ECG

Hypothermia can produce a number of changes on the ECG. At the start of hypothermia, a stress reaction is induced, resulting in sinus tachycardia. But when the temperature goes below 32°C, sinus bradycardia ensues,¹ resulting in various degrees of heart block.² In our patient, a severely prolonged PR interval resulted in first-degree heart block.

Other findings on ECG associated with hypothermia include atrial fibrillation, widening of the P and T waves, prolonging of the QT interval, and widening of the QRS interval. Progressive widening of the QRS interval can predispose to ventricular fibrillation.^1,3

An Osborn or J wave is a wave found between the end of the QRS and the beginning of the ST segment and is usually seen on the inferior and lateral precordial leads. It is found in as many as 80% of patients when the body temperature is below 30°C.^1,3,4

Although Osborn waves are a common finding in hypothermia, they are also seen in electrolyte imbalances such as hypercalcemia and in central nervous system diseases.^5,6 Hypothermia-associated changes on ECG are usually readily reversible with rewarming.¹

TAKE-HOME MESSAGES

The ECG should always be interpreted in the proper clinical context and, whenever possible, compared with a previous ECG. It is prudent to always consider potentially reversible triggers of hypothermia other than environmental exposure such as hypothyroidism, infection, adrenal insufficiency, ketoacidosis, medication side effects, and alcohol use.

Hypothermia, especially in elderly patients with multiple comorbidities, can lead to bradycardia and varying degrees of heart block.

A 96-year-old woman with hypertension, diabetes,    and dementia was found unresponsive in her nursing home and was transferred to the hospital.

At presentation to the hospital, her blood pressure was 76/43 mm Hg, heart rate 42 beats per minute, rectal temperature 31.6°C (88.8°F), and blood glucose 36 mg/dL.

The initial electrocardiogram (ECG) (Figure 1) showed sinus bradycardia with first-degree atrioventricular block and a PR interval of 704 ms. The QRS interval was mildly increased, and the corrected QT interval was mildly prolonged at 476 ms. There was also evidence of probable small Osborn waves in leads II and V₅, and leads aVF and aVL seemed reversed, as was confirmed in successive ECGs.

The patient was resuscitated with intravenous fluids and glucose and was rewarmed. Repeat ECG 3 hours later (Figure 2) revealed sinus bradycardia with first-degree atrioventricular block and a PR interval of 216 ms with a rate of 52. This time the leads were confirmed in correct position, with aVF showing negative QRS deflection. Q waves were also noted in leads III and aVF, as in previous ECGs, and suggested an old inferior wall infarction. This was not seen on the first ECG because of probable lead reversal, and the suspected Osborn waves were also less prominent in V₅ and absent in lead II. The corrected QT interval was now 465 ms, and her body temperature at this time was 32.8°C (91.0°F).

Causes of secondary hypothermia were sought. Blood and urine cultures were negative. Computed tomography of the head showed no acute intracranial abnormalities. Tests for adrenal insufficiency and hypothyroidism were negative.

HYPOTHERMIA AND THE ECG

Hypothermia can produce a number of changes on the ECG. At the start of hypothermia, a stress reaction is induced, resulting in sinus tachycardia. But when the temperature goes below 32°C, sinus bradycardia ensues,¹ resulting in various degrees of heart block.² In our patient, a severely prolonged PR interval resulted in first-degree heart block.

Other findings on ECG associated with hypothermia include atrial fibrillation, widening of the P and T waves, prolonging of the QT interval, and widening of the QRS interval. Progressive widening of the QRS interval can predispose to ventricular fibrillation.^1,3

An Osborn or J wave is a wave found between the end of the QRS and the beginning of the ST segment and is usually seen on the inferior and lateral precordial leads. It is found in as many as 80% of patients when the body temperature is below 30°C.^1,3,4

Although Osborn waves are a common finding in hypothermia, they are also seen in electrolyte imbalances such as hypercalcemia and in central nervous system diseases.^5,6 Hypothermia-associated changes on ECG are usually readily reversible with rewarming.¹

TAKE-HOME MESSAGES

The ECG should always be interpreted in the proper clinical context and, whenever possible, compared with a previous ECG. It is prudent to always consider potentially reversible triggers of hypothermia other than environmental exposure such as hypothyroidism, infection, adrenal insufficiency, ketoacidosis, medication side effects, and alcohol use.

Hypothermia, especially in elderly patients with multiple comorbidities, can lead to bradycardia and varying degrees of heart block.

A 96-year-old woman with hypertension, diabetes,    and dementia was found unresponsive in her nursing home and was transferred to the hospital.

At presentation to the hospital, her blood pressure was 76/43 mm Hg, heart rate 42 beats per minute, rectal temperature 31.6°C (88.8°F), and blood glucose 36 mg/dL.

The initial electrocardiogram (ECG) (Figure 1) showed sinus bradycardia with first-degree atrioventricular block and a PR interval of 704 ms. The QRS interval was mildly increased, and the corrected QT interval was mildly prolonged at 476 ms. There was also evidence of probable small Osborn waves in leads II and V₅, and leads aVF and aVL seemed reversed, as was confirmed in successive ECGs.

The patient was resuscitated with intravenous fluids and glucose and was rewarmed. Repeat ECG 3 hours later (Figure 2) revealed sinus bradycardia with first-degree atrioventricular block and a PR interval of 216 ms with a rate of 52. This time the leads were confirmed in correct position, with aVF showing negative QRS deflection. Q waves were also noted in leads III and aVF, as in previous ECGs, and suggested an old inferior wall infarction. This was not seen on the first ECG because of probable lead reversal, and the suspected Osborn waves were also less prominent in V₅ and absent in lead II. The corrected QT interval was now 465 ms, and her body temperature at this time was 32.8°C (91.0°F).

Causes of secondary hypothermia were sought. Blood and urine cultures were negative. Computed tomography of the head showed no acute intracranial abnormalities. Tests for adrenal insufficiency and hypothyroidism were negative.

HYPOTHERMIA AND THE ECG

Hypothermia can produce a number of changes on the ECG. At the start of hypothermia, a stress reaction is induced, resulting in sinus tachycardia. But when the temperature goes below 32°C, sinus bradycardia ensues,¹ resulting in various degrees of heart block.² In our patient, a severely prolonged PR interval resulted in first-degree heart block.

Other findings on ECG associated with hypothermia include atrial fibrillation, widening of the P and T waves, prolonging of the QT interval, and widening of the QRS interval. Progressive widening of the QRS interval can predispose to ventricular fibrillation.^1,3

An Osborn or J wave is a wave found between the end of the QRS and the beginning of the ST segment and is usually seen on the inferior and lateral precordial leads. It is found in as many as 80% of patients when the body temperature is below 30°C.^1,3,4

Although Osborn waves are a common finding in hypothermia, they are also seen in electrolyte imbalances such as hypercalcemia and in central nervous system diseases.^5,6 Hypothermia-associated changes on ECG are usually readily reversible with rewarming.¹

TAKE-HOME MESSAGES

The ECG should always be interpreted in the proper clinical context and, whenever possible, compared with a previous ECG. It is prudent to always consider potentially reversible triggers of hypothermia other than environmental exposure such as hypothyroidism, infection, adrenal insufficiency, ketoacidosis, medication side effects, and alcohol use.

Hypothermia, especially in elderly patients with multiple comorbidities, can lead to bradycardia and varying degrees of heart block.