William W. Huang, MD, MPH

The Diagnosis: Flagellate Hyperpigmentation

Physical examination of our patient revealed multiple linear, flagellate, and hyperpigmented plaques on the trunk. Similar lesions were seen on the upper and lower extremities. Given the patient's history of non-Hodgkin lymphoma and concurrent chemotherapy, the use of systemic steroids was avoided. Notable improvement in the symptoms was achieved with topical steroids (triamcinolone acetonide ointment) under occlusion and systemic gabapentin. The patient's chemotherapy is ongoing. This characteristic skin eruption often is seen after treatment with systemic bleomycin sulfate.

Flagellate hyperpigmentation following systemic bleomycin sulfate use as a chemotherapeutic agent is a well-known cutaneous reaction that occurs in approximately 10% of exposed individuals.¹ Bleomycin sul­fate, an antibiotic derived from Streptomyces verticillus, is a commonly used antitumor agent for both hema­tologic and solid-organ malignancies.² Many patients develop generalized pruritus within several days after initiating bleomycin sulfate, followed by the charac­teristic linear and hyperpigmented streaks. The exact mechanism of this characteristic rash is unknown. Suggested pathways include induction of neutrophilic eccrine hidradenitis, postinflammatory pigmentary incontinence, and altered levels of melanin due to a toxic effect of the medication. Other commonly re­ported adverse events to bleomycin sulfate include alopecia and stomatitis.³

Although a diffuse rash is the most commonly reported cutaneous reaction to systemic bleomycin sulfate, there have been reports of hyperpigmenta­tion only in areas of pressure and palmar creases. Tsuji and Sawabe⁴ reported a case of hyperpigmenta­tion limited to areas of striae distensae after systemic bleomycin sulfate. Flagellate hyperpigmentation also has been reported following intralesional bleomycin sulfate for the treatment of verruca plantaris. In that case, the patient had received 14 U of intralesional bleomycin sulfate injected at different sites of recal­citrant verruca and developed urticaria, generalized pruritus, and flagellate hyperpigmentation.⁵

Treatment of flagellate hyperpigmentation in­cludes cessation of the medication, which is not always possible due to the need for an effective che­motherapeutic regimen. Most cases are reversible following discontinuation of bleomycin sulfate, and care is directed at symptom relief with antipruritic agents, antihistamines, systemic steroids, or topical steroids.³

The Diagnosis: Flagellate Hyperpigmentation

Physical examination of our patient revealed multiple linear, flagellate, and hyperpigmented plaques on the trunk. Similar lesions were seen on the upper and lower extremities. Given the patient's history of non-Hodgkin lymphoma and concurrent chemotherapy, the use of systemic steroids was avoided. Notable improvement in the symptoms was achieved with topical steroids (triamcinolone acetonide ointment) under occlusion and systemic gabapentin. The patient's chemotherapy is ongoing. This characteristic skin eruption often is seen after treatment with systemic bleomycin sulfate.

Flagellate hyperpigmentation following systemic bleomycin sulfate use as a chemotherapeutic agent is a well-known cutaneous reaction that occurs in approximately 10% of exposed individuals.¹ Bleomycin sul­fate, an antibiotic derived from Streptomyces verticillus, is a commonly used antitumor agent for both hema­tologic and solid-organ malignancies.² Many patients develop generalized pruritus within several days after initiating bleomycin sulfate, followed by the charac­teristic linear and hyperpigmented streaks. The exact mechanism of this characteristic rash is unknown. Suggested pathways include induction of neutrophilic eccrine hidradenitis, postinflammatory pigmentary incontinence, and altered levels of melanin due to a toxic effect of the medication. Other commonly re­ported adverse events to bleomycin sulfate include alopecia and stomatitis.³

Although a diffuse rash is the most commonly reported cutaneous reaction to systemic bleomycin sulfate, there have been reports of hyperpigmenta­tion only in areas of pressure and palmar creases. Tsuji and Sawabe⁴ reported a case of hyperpigmenta­tion limited to areas of striae distensae after systemic bleomycin sulfate. Flagellate hyperpigmentation also has been reported following intralesional bleomycin sulfate for the treatment of verruca plantaris. In that case, the patient had received 14 U of intralesional bleomycin sulfate injected at different sites of recal­citrant verruca and developed urticaria, generalized pruritus, and flagellate hyperpigmentation.⁵

Treatment of flagellate hyperpigmentation in­cludes cessation of the medication, which is not always possible due to the need for an effective che­motherapeutic regimen. Most cases are reversible following discontinuation of bleomycin sulfate, and care is directed at symptom relief with antipruritic agents, antihistamines, systemic steroids, or topical steroids.³

The Diagnosis: Flagellate Hyperpigmentation

Physical examination of our patient revealed multiple linear, flagellate, and hyperpigmented plaques on the trunk. Similar lesions were seen on the upper and lower extremities. Given the patient's history of non-Hodgkin lymphoma and concurrent chemotherapy, the use of systemic steroids was avoided. Notable improvement in the symptoms was achieved with topical steroids (triamcinolone acetonide ointment) under occlusion and systemic gabapentin. The patient's chemotherapy is ongoing. This characteristic skin eruption often is seen after treatment with systemic bleomycin sulfate.

Flagellate hyperpigmentation following systemic bleomycin sulfate use as a chemotherapeutic agent is a well-known cutaneous reaction that occurs in approximately 10% of exposed individuals.¹ Bleomycin sul­fate, an antibiotic derived from Streptomyces verticillus, is a commonly used antitumor agent for both hema­tologic and solid-organ malignancies.² Many patients develop generalized pruritus within several days after initiating bleomycin sulfate, followed by the charac­teristic linear and hyperpigmented streaks. The exact mechanism of this characteristic rash is unknown. Suggested pathways include induction of neutrophilic eccrine hidradenitis, postinflammatory pigmentary incontinence, and altered levels of melanin due to a toxic effect of the medication. Other commonly re­ported adverse events to bleomycin sulfate include alopecia and stomatitis.³

Although a diffuse rash is the most commonly reported cutaneous reaction to systemic bleomycin sulfate, there have been reports of hyperpigmenta­tion only in areas of pressure and palmar creases. Tsuji and Sawabe⁴ reported a case of hyperpigmenta­tion limited to areas of striae distensae after systemic bleomycin sulfate. Flagellate hyperpigmentation also has been reported following intralesional bleomycin sulfate for the treatment of verruca plantaris. In that case, the patient had received 14 U of intralesional bleomycin sulfate injected at different sites of recal­citrant verruca and developed urticaria, generalized pruritus, and flagellate hyperpigmentation.⁵

Treatment of flagellate hyperpigmentation in­cludes cessation of the medication, which is not always possible due to the need for an effective che­motherapeutic regimen. Most cases are reversible following discontinuation of bleomycin sulfate, and care is directed at symptom relief with antipruritic agents, antihistamines, systemic steroids, or topical steroids.³

1. Tetracyclines work via:

a. blocking the transpeptidation step of cell wall synthesis

b. inhibiting penicillin-binding proteins of transpeptidation

c. inhibiting protein synthesis by binding the 30S ribosomal subunit of messenger RNA

d. inhibiting protein synthesis by binding the 50S ribosomal subunit of messenger RNA

e. inhibiting DNA gyrase

2. Which of the following does not require viral thymidine kinase phosphorylation to work?

a. cidofovir

b. famciclovir

c. ganciclovir

d. penciclovir

e. valacyclovir

3. After taking an antibiotic, a patient notices that his tears are orange-red in color. Which of the following is the most likely cause?

a. cephalosporins

b. cidofovir

c. fluoroquinolones

d. foscarnet

e. rifampin

4. Which of the following is most commonly associated with pseudomembranous colitis?

a. azithromycin

b. cephalexin

c. clindamycin

d. doxycycline

e. rifampin

5. Penile ulcers have been reported in patients taking which of the following:

a. acyclovir

b. cidofovir

c. foscarnet

d. ganciclovir

e. penciclovir

1. Tetracyclines work via:

a. blocking the transpeptidation step of cell wall synthesis

b. inhibiting penicillin-binding proteins of transpeptidation

c. inhibiting protein synthesis by binding the 30S ribosomal subunit of messenger RNA

d. inhibiting protein synthesis by binding the 50S ribosomal subunit of messenger RNA

e. inhibiting DNA gyrase

2. Which of the following does not require viral thymidine kinase phosphorylation to work?

a. cidofovir

b. famciclovir

c. ganciclovir

d. penciclovir

e. valacyclovir

3. After taking an antibiotic, a patient notices that his tears are orange-red in color. Which of the following is the most likely cause?

a. cephalosporins

b. cidofovir

c. fluoroquinolones

d. foscarnet

e. rifampin

4. Which of the following is most commonly associated with pseudomembranous colitis?

a. azithromycin

b. cephalexin

c. clindamycin

d. doxycycline

e. rifampin

5. Penile ulcers have been reported in patients taking which of the following:

a. acyclovir

b. cidofovir

c. foscarnet

d. ganciclovir

e. penciclovir

1. Tetracyclines work via:

a. blocking the transpeptidation step of cell wall synthesis

b. inhibiting penicillin-binding proteins of transpeptidation

c. inhibiting protein synthesis by binding the 30S ribosomal subunit of messenger RNA

d. inhibiting protein synthesis by binding the 50S ribosomal subunit of messenger RNA

e. inhibiting DNA gyrase

2. Which of the following does not require viral thymidine kinase phosphorylation to work?

a. cidofovir

b. famciclovir

c. ganciclovir

d. penciclovir

e. valacyclovir

3. After taking an antibiotic, a patient notices that his tears are orange-red in color. Which of the following is the most likely cause?

a. cephalosporins

b. cidofovir

c. fluoroquinolones

d. foscarnet

e. rifampin

4. Which of the following is most commonly associated with pseudomembranous colitis?

a. azithromycin

b. cephalexin

c. clindamycin

d. doxycycline

e. rifampin

5. Penile ulcers have been reported in patients taking which of the following:

a. acyclovir

b. cidofovir

c. foscarnet

d. ganciclovir

e. penciclovir

1. Which of the following muscles is not directly involved in smiling?
a. orbicularis oris
b. risorius
c. zygomaticus major
d. zygomaticus minor

2. Which represents the most robust connection between the internal carotid and external carotid arteries?
a. angular→dorsal nasal
b. infraorbital→angular
c. superior labial→lateral nasal
d. superficial temporal→infraorbital

3. Which muscle is not used during deep inspiration to flare the nares?
a. depressor septi nasi
b. levator labii superioris alaeque nasi
c. nasalis
d. procerus

4. Which muscle receives its innervations from its superficial surface?
a. buccinator
b. depressor anguli oris
c. frontalis
d. mentalis

5. Blood supply to the chin is primarily from what branch of the external carotid artery?
a. inferior labial
b. maxillary
c. ophthalmic
d. superficial temporal

1. Which of the following muscles is not directly involved in smiling?
a. orbicularis oris
b. risorius
c. zygomaticus major
d. zygomaticus minor

2. Which represents the most robust connection between the internal carotid and external carotid arteries?
a. angular→dorsal nasal
b. infraorbital→angular
c. superior labial→lateral nasal
d. superficial temporal→infraorbital

3. Which muscle is not used during deep inspiration to flare the nares?
a. depressor septi nasi
b. levator labii superioris alaeque nasi
c. nasalis
d. procerus

4. Which muscle receives its innervations from its superficial surface?
a. buccinator
b. depressor anguli oris
c. frontalis
d. mentalis

5. Blood supply to the chin is primarily from what branch of the external carotid artery?
a. inferior labial
b. maxillary
c. ophthalmic
d. superficial temporal

1. Which of the following muscles is not directly involved in smiling?
a. orbicularis oris
b. risorius
c. zygomaticus major
d. zygomaticus minor

2. Which represents the most robust connection between the internal carotid and external carotid arteries?
a. angular→dorsal nasal
b. infraorbital→angular
c. superior labial→lateral nasal
d. superficial temporal→infraorbital

3. Which muscle is not used during deep inspiration to flare the nares?
a. depressor septi nasi
b. levator labii superioris alaeque nasi
c. nasalis
d. procerus

4. Which muscle receives its innervations from its superficial surface?
a. buccinator
b. depressor anguli oris
c. frontalis
d. mentalis

5. Blood supply to the chin is primarily from what branch of the external carotid artery?
a. inferior labial
b. maxillary
c. ophthalmic
d. superficial temporal

1. The most commonly used substrate for indirect immunofluorescence in diagnosing paraneoplastic pemphigus is:

a. guinea pig esophagus
b. monkey bladder
c. monkey esophagus
d. rat bladder
e. rat esophagus

2. Which solid organ malignancy is most commonly associated with paraneoplastic Sweet syndrome in men?

a. bladder
b. brain
c. gastrointestinal
d. lung
e. renal

3. A patient with necrolytic migratory erythema and glucagonoma syndrome can be expected to have the following abnormal laboratory results:
a. elevated amino acid levels
b. elevated red blood cell count
c. elevated serum glucagon levels
d. elevated zinc level
e. low serum glucagon levels

4. Leser-Trélat sign has been reported to present with which of the following:
a. acanthosis nigricans
b. acquired ichthyosis
c. severe pruritus
d. tripe palms
e. all of the above

5. Which of the following is most strongly associated with an increased risk for malignancy in dermatomyositis?
a. anti-Mi2 autoantibody
b. anti-p155 autoantibody
c. elevated erythrocyte sedimentation rate
d. positive antinuclear antibody
e. positive double-stranded DNA

1. The most commonly used substrate for indirect immunofluorescence in diagnosing paraneoplastic pemphigus is:

a. guinea pig esophagus
b. monkey bladder
c. monkey esophagus
d. rat bladder
e. rat esophagus

2. Which solid organ malignancy is most commonly associated with paraneoplastic Sweet syndrome in men?

a. bladder
b. brain
c. gastrointestinal
d. lung
e. renal

3. A patient with necrolytic migratory erythema and glucagonoma syndrome can be expected to have the following abnormal laboratory results:
a. elevated amino acid levels
b. elevated red blood cell count
c. elevated serum glucagon levels
d. elevated zinc level
e. low serum glucagon levels

4. Leser-Trélat sign has been reported to present with which of the following:
a. acanthosis nigricans
b. acquired ichthyosis
c. severe pruritus
d. tripe palms
e. all of the above

5. Which of the following is most strongly associated with an increased risk for malignancy in dermatomyositis?
a. anti-Mi2 autoantibody
b. anti-p155 autoantibody
c. elevated erythrocyte sedimentation rate
d. positive antinuclear antibody
e. positive double-stranded DNA

1. The most commonly used substrate for indirect immunofluorescence in diagnosing paraneoplastic pemphigus is:

a. guinea pig esophagus
b. monkey bladder
c. monkey esophagus
d. rat bladder
e. rat esophagus

2. Which solid organ malignancy is most commonly associated with paraneoplastic Sweet syndrome in men?

a. bladder
b. brain
c. gastrointestinal
d. lung
e. renal

3. A patient with necrolytic migratory erythema and glucagonoma syndrome can be expected to have the following abnormal laboratory results:
a. elevated amino acid levels
b. elevated red blood cell count
c. elevated serum glucagon levels
d. elevated zinc level
e. low serum glucagon levels

4. Leser-Trélat sign has been reported to present with which of the following:
a. acanthosis nigricans
b. acquired ichthyosis
c. severe pruritus
d. tripe palms
e. all of the above

5. Which of the following is most strongly associated with an increased risk for malignancy in dermatomyositis?
a. anti-Mi2 autoantibody
b. anti-p155 autoantibody
c. elevated erythrocyte sedimentation rate
d. positive antinuclear antibody
e. positive double-stranded DNA

1. A 17-year-old adolescent girl presents to the emergency department with breathing trouble. She has no history of respiratory disease and no medical history of consequence. After leaving an uncomplicated laser hair removal appointment, she developed shortness of breath. On examination she is tachypneic and tachycardic with a pulse oximetry of 88% on 90% nonrebreather mask. What is the appropriate course of action?

a. epinephrine and intravenous diphenhydramine

b. intravenous methylene blue (1 mg/kg)

c. intravenous methylprednisolone sodium succinate (Solu-Medrol, Pharmacia & Upjohn Co)

d. oxygen and nebulizer treatments

e. spiral chest computed tomography

2. Which is the most likely order of symptoms in a patient with increasing lidocaine toxicity?

a. coma, anxiety, disorientation, focal seizures

b. nausea, bradypnea, metallic taste, dizziness

c. perioral numbness, diplopia, bradycardia, cardiac arrest

d. seizure, somnolence, vomiting, coma

e. slurred speech, dizziness, bradycardia, tinnitus, seizure

3. What is the maximum amount of 1% lidocaine (with epinephrine) that can be safely administered to a 50-kg healthy adult?

a. 150 mg

b. 175 mg

c. 200 mg

d. 250 mg

e. 350 mg

4. Which of the following will not decrease pain from local administration of lidocaine for most patients?

a. addition of sodium bicarbonate to the preparation

b. background music or conversation

c. quick administration

d. tapping the skin

e. warming the anesthetic

5. Which of the following can be safely used in a patient with a p-aminobenzoic acid allergy?

a. chloroprocaine

b. lidocaine (preservative free)

c. procaine

d. proparacaine

e. tetracaine

1. A 17-year-old adolescent girl presents to the emergency department with breathing trouble. She has no history of respiratory disease and no medical history of consequence. After leaving an uncomplicated laser hair removal appointment, she developed shortness of breath. On examination she is tachypneic and tachycardic with a pulse oximetry of 88% on 90% nonrebreather mask. What is the appropriate course of action?

a. epinephrine and intravenous diphenhydramine

b. intravenous methylene blue (1 mg/kg)

c. intravenous methylprednisolone sodium succinate (Solu-Medrol, Pharmacia & Upjohn Co)

d. oxygen and nebulizer treatments

e. spiral chest computed tomography

2. Which is the most likely order of symptoms in a patient with increasing lidocaine toxicity?

a. coma, anxiety, disorientation, focal seizures

b. nausea, bradypnea, metallic taste, dizziness

c. perioral numbness, diplopia, bradycardia, cardiac arrest

d. seizure, somnolence, vomiting, coma

e. slurred speech, dizziness, bradycardia, tinnitus, seizure

3. What is the maximum amount of 1% lidocaine (with epinephrine) that can be safely administered to a 50-kg healthy adult?

a. 150 mg

b. 175 mg

c. 200 mg

d. 250 mg

e. 350 mg

4. Which of the following will not decrease pain from local administration of lidocaine for most patients?

a. addition of sodium bicarbonate to the preparation

b. background music or conversation

c. quick administration

d. tapping the skin

e. warming the anesthetic

5. Which of the following can be safely used in a patient with a p-aminobenzoic acid allergy?

a. chloroprocaine

b. lidocaine (preservative free)

c. procaine

d. proparacaine

e. tetracaine

1. A 17-year-old adolescent girl presents to the emergency department with breathing trouble. She has no history of respiratory disease and no medical history of consequence. After leaving an uncomplicated laser hair removal appointment, she developed shortness of breath. On examination she is tachypneic and tachycardic with a pulse oximetry of 88% on 90% nonrebreather mask. What is the appropriate course of action?

a. epinephrine and intravenous diphenhydramine

b. intravenous methylene blue (1 mg/kg)

c. intravenous methylprednisolone sodium succinate (Solu-Medrol, Pharmacia & Upjohn Co)

d. oxygen and nebulizer treatments

e. spiral chest computed tomography

2. Which is the most likely order of symptoms in a patient with increasing lidocaine toxicity?

a. coma, anxiety, disorientation, focal seizures

b. nausea, bradypnea, metallic taste, dizziness

c. perioral numbness, diplopia, bradycardia, cardiac arrest

d. seizure, somnolence, vomiting, coma

e. slurred speech, dizziness, bradycardia, tinnitus, seizure

3. What is the maximum amount of 1% lidocaine (with epinephrine) that can be safely administered to a 50-kg healthy adult?

a. 150 mg

b. 175 mg

c. 200 mg

d. 250 mg

e. 350 mg

4. Which of the following will not decrease pain from local administration of lidocaine for most patients?

a. addition of sodium bicarbonate to the preparation

b. background music or conversation

c. quick administration

d. tapping the skin

e. warming the anesthetic

5. Which of the following can be safely used in a patient with a p-aminobenzoic acid allergy?

a. chloroprocaine

b. lidocaine (preservative free)

c. procaine

d. proparacaine

e. tetracaine

1. Which of the following enzymes of the heme synthesis pathway is found in the mitochondria?

a. δ-aminolevulinic oxidase

b. porphobilinogen deaminase

c. protoporphyrinogen oxidase

d. uroporphyrinogen decarboxylase

e. uroporphyrinogen III synthase

2. A patient with variegate porphyria uniquely has plasma fluorescence at the following wavelength:

a. 311 nm

b. 366 nm

c. 410 nm

d. 626 nm

e. 630 nm

3. What laboratory result would be expected to be abnormal in a patient with a defect in ferrochelatase?

a. elevated δ-aminolevulinic acid

b. elevated erythrocyte protoporphyrins

c. elevated fecal coproporphyrins

d. elevated urinary porphobilinogen

e. elevated urinary uroporphyrins

4. What clinical feature would be present in a newborn diagnosed with transient erythroporphyria of infancy?

a. dark red urine

b. immediate burning photosensitivity

c. red teeth that fluoresce under Wood lamp

d. skin purpura

e. urine that fluoresces pink under Wood lamp

5. What medication should be avoided in a patient with a defect in porphobilinogen deaminase?

a. captopril

b. furosemide

c. griseofulvin

d. naproxen

e. tetracyclines

1. Which of the following enzymes of the heme synthesis pathway is found in the mitochondria?

a. δ-aminolevulinic oxidase

b. porphobilinogen deaminase

c. protoporphyrinogen oxidase

d. uroporphyrinogen decarboxylase

e. uroporphyrinogen III synthase

2. A patient with variegate porphyria uniquely has plasma fluorescence at the following wavelength:

a. 311 nm

b. 366 nm

c. 410 nm

d. 626 nm

e. 630 nm

3. What laboratory result would be expected to be abnormal in a patient with a defect in ferrochelatase?

a. elevated δ-aminolevulinic acid

b. elevated erythrocyte protoporphyrins

c. elevated fecal coproporphyrins

d. elevated urinary porphobilinogen

e. elevated urinary uroporphyrins

4. What clinical feature would be present in a newborn diagnosed with transient erythroporphyria of infancy?

a. dark red urine

b. immediate burning photosensitivity

c. red teeth that fluoresce under Wood lamp

d. skin purpura

e. urine that fluoresces pink under Wood lamp

5. What medication should be avoided in a patient with a defect in porphobilinogen deaminase?

a. captopril

b. furosemide

c. griseofulvin

d. naproxen

e. tetracyclines

1. Which of the following enzymes of the heme synthesis pathway is found in the mitochondria?

a. δ-aminolevulinic oxidase

b. porphobilinogen deaminase

c. protoporphyrinogen oxidase

d. uroporphyrinogen decarboxylase

e. uroporphyrinogen III synthase

2. A patient with variegate porphyria uniquely has plasma fluorescence at the following wavelength:

a. 311 nm

b. 366 nm

c. 410 nm

d. 626 nm

e. 630 nm

3. What laboratory result would be expected to be abnormal in a patient with a defect in ferrochelatase?

a. elevated δ-aminolevulinic acid

b. elevated erythrocyte protoporphyrins

c. elevated fecal coproporphyrins

d. elevated urinary porphobilinogen

e. elevated urinary uroporphyrins

4. What clinical feature would be present in a newborn diagnosed with transient erythroporphyria of infancy?

a. dark red urine

b. immediate burning photosensitivity

c. red teeth that fluoresce under Wood lamp

d. skin purpura

e. urine that fluoresces pink under Wood lamp

5. What medication should be avoided in a patient with a defect in porphobilinogen deaminase?

a. captopril

b. furosemide

c. griseofulvin

d. naproxen

e. tetracyclines