Paclitaxel-associated reticulate hyperpigmentation: Report and review of chemotherapy-induced reticulate hyperpigmentation

Table 1 Characteristics of patients with chemotherapy-induced reticulate hyperpigmentation

Case	Age (yr) Race Sex	Chemo	Onset (d)	OCF	Site	Histo	Cancer	Seq	Ref.
1	55 NR M	Adria Bleo1 Cyclo MTX Vin	42	None	Arms Back Legs2	DM MBaK MSBaK EM3	NHL	Persists	6
2	61 Ca M	5-FU14	3	CAE	Back2	NR	GIT	Faded5	7
3	64 Ca M	Cyt1 Ida1 Lo	21	None	Back Butt	NR	AML	UK	8C5
4	74 Ca M	Cyclo Cyt1 Dexa Ida1 Vin	28	Mild Pru	Back Shdr	MBaK MPaD PI	ALL	Faded6	8C2
5	49 Ca W	Pac1	126	None	Back Thi	MBaK MPaD PI	BC	Faded7	8C1
6	51 NR W	Cyt1 Ida1	> 28	None	Back (low)	NR	AML	NR	9C2
7	55 Ta W	Pac1	< 7	None	Abd Back Legs	DM MBaK PI	BC8	Faded9	CR
8	61 Ca W	Cyt1 Top	28	None	Back Butt Thi	RCM10	AML	UK	8C4
9	63 NR W	Carbo 5-FU1	311	PAE	Back Butt Thi	NR	MEC	NR	9C1
10	74 Ca W	Carbo Pac1	42	PAE Pru	Back	RCM10	OC	Faded12	8C3

¹Suspected chemotherapeutic agent causing reticulate hyperpigmentation;

²The hyperpigmentation was widespread;

³Electron microscopy showed: (1) a normal number of melanocytes and (2) an increased number of melanosomes in keratinocytes;

⁴Pigmentation occurred at 400 mg/m³ (680 mg). It did not occur at 200 mg/m³ (340 mg). The dose was increased to 400 mg/m³ and there was no subsequent recurrence;

⁵The hyperpigmentation faded over 16 wk;

⁶The hyperpigmentation faded within 6 mo;

⁷The hyperpigmentation faded within 3 mo;

⁸The patient had mixed lobular and ductal breast cancer metastatic to bone, liver and lungs;

⁹Paclitaxel was discontinued after her 7^th weekly treatment. At follow-up 2 mo after stopping paclitaxel, the hyperpigmentation was completely faded on her abdomen and legs. There was also significant fading on her back and arms;

¹⁰Reflectance confocal microscopy showed increased amount of melanin in basal keratinocytes;

¹¹Hyperpigmentation appeared 3 d after starting cycle 3 of chemotherapy;

¹²Slight regression of the hyperpigmentation was observed. Abd: Abdomen; Adria: Adriamycin; ALL: Acute lymphoblastic leukemia; AML: Acute myelogenous leukemia; BC: Breast cancer (metastatic); Bleo: Bleomycin; Butt: Buttocks; Ca: Caucasian; CAE: Concurrent asymptomatic erythema; Carbo: Carboplatin; Chemo: Chemotherapy patient was being treated with; CR: Current report; Cyclo: Cyclophosphamide; Cyt: Cytarabine; Dexa: Dexamethasone; DM: Dermal (papillary) melanophages; EM: Electron microscopy; 5-FU: 5-fluorouracil; GIT: Gastrointestinal carcinoma (metastatic); Histo: Histopathology (hematoxylin and eosin or Fontana Masson or both); Ida: Idarubicin; Lo: Lomustine; Low: Lower; M: Man; MEC: Mucoid epidermoid carcinoma of the parotic gland; MBaK: Melanin increased in basal keratinocytes; MPaD: Melanin in papillary dermis; MSBaK: Melanin increased in suprabasal keratinocytes; MTX: Methotrexate; NHL: Non-Hodgkin lymphoma; NR: Not reported; OC: Ovarian cancer (metastatic); OCF: Other clinical features; Pac: Paclitaxel; PAE: Preexisting asymptomatic erythema; PI: Pigmentary incontinence into the papillary dermis; Pru: Pruritus; RCM: Reflectance confocal microscopy; Seq: Sequellae; Shdr: Shoulders; Symp: Symptoms; Ta: Taiwanese; Thi: Thighs; Top: Topoisomerase II inhibitor; UK: Unknown; Vin: Vincristine; W: Woman.

Table 2 Adverse drug reaction probability scale^1,2,3,4

Question	PA	PS
Are there previous conclusive reports on this reaction?	Yes	1
Answer score: Yes = +1; No = 0
Did the adverse event appear after the suspected drug was administered?	Yes	2
Answer score: Yes = +2; No = -1
Did the adverse reaction improve when the drug was discontinued or a specific antagonist was administered?	Yes	1
Answer score: Yes = +1; No = 0
Did the adverse reaction reappear when the drug was readministered?	Yes	2
Answer score: Yes = +2; No = -1
Are there alternative causes (other than the drug) that could on their own have caused the reaction?	No	2
Answer score: Yes = -1; No = +2
Did the reaction reappear when a placebo was given?	DNK	0
Answer score: Yes = -1; No = +1
Was the drug detected in the blood (or other fluids) in concentrations known to be toxic?	DNK	0
Answer score: Yes = +1; No = 0
Was the reaction more severe when the dose was increased, or less severe when the dose was decreased?	DNK	0
Answer score: Yes = +1; No = 0
Did the patient have a similar reaction to the same or similar drugs in any previous exposure?	DNK	0
Answer score: Yes = +1; No = 0
Was the adverse event confirmed by any objective evidence?	Yes	1
Answer score: Yes = +1; No = 0
Total score		9

¹An answer is provided for all questions (PA) and a determination of score is provided (PS) to assess the adverse drug reaction; ²An answer of “Do not know” = 0 score; ³From the total score, the adverse drug reaction is assigned a probability category: Definite (greater than or equal to 9), probable (5 to 8), possible (1 to 4), doubtful (less than or equal to 0); ⁴Drug = paclitaxel. DNK: Do not know; PA: Patient answer; PS: Patient score.