Serpentine supravenous hyperpigmentation and an atypical presentation of hand-foot syndrome in the setting of docetaxel therapy

Introduction

Serpentine supravenous hyperpigmentation (SSH) and hand-foot syndrome (HFS) are well-described cutaneous complications associated with cytotoxic chemotherapy agents such as docetaxel.¹ SSH is a rare and distinctive cutaneous eruption associated with peripheral infusion of certain antineoplastic agents. HFS is a more common adverse reaction that typically presents as painful erythema of the palms and soles.² However, in cases of docetaxel-induced HFS, the eruption characteristically involves the dorsal aspects of the hands.¹ We present a unique case of concurrent SSH and HFS following docetaxel infusion, with an unusual presentation of HFS involving both the dorsal and palmar surfaces of the hands and fingers.

Case report

A 61-year-old female patient with stage 1b triple-negative invasive ductal carcinoma of the right breast, status post partial mastectomy, was started on adjuvant chemotherapy with docetaxel and cyclophosphamide. Her first infusion included docetaxel (166 mg [75 mg/mm²] in 250 mL of sodium chloride 0.9%) administered through a peripheral IV in the right distal forearm. Two days following the infusion, the patient developed a hyperpigmented rash on the right forearm. Two weeks later, she developed desquamation of the hands and feet that was refractory to topical moisturizers.

The patient was seen in the dermatology clinic 3 weeks after the infusion. Physical exam was notable for a large, hyperpigmented, slightly scaly, curvilinear plaque spanning the entire length of the right dorsal forearm (Fig 1). There was also erythema and mild desquamation of the bilateral palms, with continuation of the rash onto the dorsal aspects of the fingers (Fig 2, A and B). Given the onset of symptoms following the initiation of cytotoxic chemotherapy, these findings were thought to be consistent with docetaxel-induced SSH and HFS. The patient was prescribed clobetasol ointment for the hands and instructed to apply petroleum-based emollients to the lesion on the right dorsal forearm. Recommendations to her oncologist included placement of a central venous catheter for future infusions and cooling therapy for the hands and feet during treatments.

Fig 1.

Serpentine supravenous hyperpigmentation. Large hyperpigmented scaly plaque on the right dorsal forearm with characteristic “serpentine” morphology.

Fig 2.

Docetaxel-induced hand-foot syndrome. A, Erythema and desquamation of the bilateral palms. B, Extension of the erythema and scaling onto the dorsal fingers, with prominence over the proximal interphalangeal joints.

Chemotherapy infusions were paused for several weeks. When treatment was resumed, docetaxel was replaced with paclitaxel, and the infusions were administered through the patient’s newly implanted central chemotherapy port. Cooling therapy of the hands and feet was also introduced. The patient returned to the dermatology clinic approximately 8 weeks after her initial visit. At that time, there was no visible rash on the dorsal fingers and only minimal scaling of the palms. The hyperpigmented plaque on the right dorsal forearm was mostly unchanged, other than resolution of the overlying scale, but she had no further episodes of SSH.

Discussion

Docetaxel, a hemisynthetic product derived from the European yew tree (Taxus baccata), is a chemotherapeutic agent used in the treatment of various malignancies, including breast cancer.¹ The cutaneous adverse effects are well-documented, although exact incidence rates in the literature vary. Skin reactions are dose-dependent and encompass mild to moderate rashes, nail changes, alopecia, and mucositis. Docetaxel has also been implicated in several unique cutaneous toxicities, including SSH and dorsal HFS.¹

SSH is a rare reaction that presents as a fixed erythematous or violaceous plaque at the site of docetaxel infusion that extends proximally along venous pathways and may progress to persistent hyperpigmentation.³ These lesions develop between 1 day and 2 weeks postchemotherapy and slowly resolve over months following cessation of the peripheral chemotherapy infusion (Table I). The exact pathogenesis of SSH is unclear. One theory suggests that the hyperpigmentation in SSH may be due to a direct toxic effect of docetaxel on epidermal melanocytes. This may occur, for example, if there is inadequate venous washing after infusion, allowing local diffusion of the drug out of the vessels with subsequent toxic injury to the epidermis. These findings are supported on skin biopsies which demonstrate epidermal atrophy, diffuse basilar hyperpigmentation, and subtle basal vacuolar alteration with scattered necrotic keratinocytes.⁴ Currently, there are no established guidelines for prevention of SSH, though recommendations include saline infusions before and after chemotherapy, central venous access, and oral corticosteroids to suppress inflammation. Management involves immediate drug cessation, limb elevation, cold compresses, and steroidal agents.³

Table I.

Characteristics of serpentine supravenous hyperpigmentation (SSH) and hand-foot syndrome (HFS)

	Serpentine supravenous hyperpigmentation	Hand-foot syndrome
Cause	Peripheral infusion of certain chemotherapeutic agents	Adverse chemotherapy reaction; may be exacerbated by pressure, friction, or UV exposure
Onset	1 day to 2 weeks postinfusion	Variable onset; days to weeks postinfusion
Location	Occurs at infusion site and extends proximally along venous pathways	Palms and soles with most antineoplastic agents Dorsal hand involvement with docetaxel; palms may be affected simultaneously
Appearance	Erythematous/hyperpigmented patches with branching configuration along superficial venous pathways	Erythema, edema, and/or scaling of palms and soles
Proposed pathogenesis	Drug leakage and local toxicity to epidermal keratinocytes and melanocytes	Direct toxic effect on epidermis
Histopathology	Epidermal atrophy, sparse basal vacuolar alteration with necrotic keratinocytes, hyperpigmentation of basal epidermis	Epidermal dysmaturation, keratinocyte atypia, bizarre mitotic figures, basal vacuolar change, necrotic keratinocytes
Management	Emollients, topical steroids, cool compresses, administer chemotherapy through central venous catheter	Emollients, topical steroids, cooling therapy to hands and feet, limb elevation, high-dose vitamin D, alteration or cessation of chemotherapy regimen

HFS is more common than SSH, affecting 5% to 10% of patients undergoing taxane-based chemotherapy.¹ HFS is considered under the umbrella term “toxic erythema of chemotherapy”, which encompasses various cytotoxic reactions resulting in painful erythema of the skin.⁵ The manifestations of conventional chemotherapy-induced HFS due to agents such as doxorubicin and capecitabine include palmoplantar dysesthesias and the development of well-demarcated, erythematous, edematous plaques on the palms and soles, extending to the lateral aspects of the fingers.⁶ In contrast, docetaxel-induced HFS characteristically occurs as a scaly, erythematous eruption on the dorsal aspects of the hands and fingers, although instances of concurrent palmoplantar involvement have been reported.⁷ Our patient displayed a combination of morphologies. The erythema and scaling of her palms extended over the lateral and dorsal aspects of the fingers, where there was prominent scaling and hyperpigmentation over the proximal interphalangeal joints. Similar clinical presentations have been seen in association with docetaxel treatment.⁷ It is unclear if the dorsal manifestations seen in docetaxel-induced HFS could be attributed to a phototoxic phenomenon, as other photo-induced dermatoses, such as drug-induced lupus erythematosus and UV recall reactions, have been seen in the setting of docetaxel therapy.^1,8 In addition, our patient regularly undergoes cosmetic nail treatments requiring the use of a UV nail lamp. It is unclear if this additional UV exposure may have contributed to the scaly eruption on the dorsal fingers.

While chemotherapy cessation remains the most effective treatment for HFS, various other strategies may help alleviate or prevent symptoms. These include reduction in the dosage or frequency of chemotherapy infusions, topical steroids, regional cooling therapy, occlusive dressings, and high-dose vitamin D.^6,9 In our patient, potent topical steroids and cooling therapy with frozen gloves and socks for 15-30 minutes before and during treatment contributed to her clinical improvement. Cooling is thought to work by inducing local vasoconstriction, reducing the amount of drug that reaches the distal extremities, and decreasing the severity of cutaneous toxicities.⁹ In addition, the several-week pause in chemotherapy and the transition from docetaxel to paclitaxel also likely played a role in the patient’s symptom resolution. There have been other case reports of dramatic improvement in HFS after switching from docetaxel to paclitaxel (Table II).¹⁰ This may be explained by the heightened intracellular retention of docetaxel relative to paclitaxel.¹⁰ Further understanding of the mechanistic differences between these agents could inform future treatment strategies to maintain anticancer therapeutic efficacy while minimizing side effects.

Table II.

Review of similar cases and agents implicated

Case report	Demographics	Agent	Manifestation of SSH	Manifestation of HFS	Management
Fernandes et al, 20153	68 y/o female	Docetaxel	Erythematous, hyperpigmented patches following venous pathways on left forearm	Not reported	Topical steroids
Fernandes et al, 20153	65 y/o female	Docetaxel	Erythematous, hyperpigmented macules and patches on left dorsal hand and forearm	Not reported	Topical steroids
Stravodimou et al, 20127	65 y/o female	Docetaxel	Not reported	Painful, pruritic, erythematous, desquamating rash on palms and soles with involvement of dorsal hands and feet	Emollients, topical steroids, discontinuation of docetaxel
Aydogan et al, 20054	46 y/o male	Docetaxel	Erythematous, hyperpigmented eruption along superficial venous network on anterior forearm	Not reported	Changing infusion site, abundant venous washing
Corazza et al, 201410	60 y/o female	Docetaxel	Not reported	Painful, erythematous-violaceous plaques on dorsal/palmar hands, dorsal/lateral feet, and axillae	Emollients, topical steroids, switching from docetaxel to paclitaxel infusions

HFS, Hand-foot syndrome; SSH, serpentine supravenous hyperpigmentation.

In conclusion, our case underscores the diverse clinical presentation of taxane-associated cutaneous reactions. These dermatologic complications pose significant challenges in diagnosis and management, especially when considering the imperative of continuing curative chemotherapy for cancer patients. Moreover, we emphasize the multifactorial nature of these conditions and urge the consideration of lifestyle factors, as some reactions may be precipitated by UV exposure. Overall, our findings highlight the need for further studies to elucidate the underlying mechanisms and optimize therapeutic strategies for these complex taxane-induced cutaneous toxicities.

Conflicts of interest

None disclosed.