biological basis of keloid formation lies on the substantial proliferation, apoptosis inhibition of

fibroblasts and imbalance between collagen synthesis and degradation. 12,13 Keloid fibroblasts are
considered to proliferate more rapidly, with oversecretion of type I collagen fibers and high
expression levels of vascular endothelial growth factor, transforming growth factor- β1̸β2 and
platelet-derived growth factor-α.12 TGF-β has been implicated in the collagen synthesis1 by
increasing the effect of epidermal growth factor (EGF) in fibroblast population, which stimulates
epithel differentiation and initiates DNA and RNA synthesis. 8

5-fluorouracil is administered once every one or two weeks, up to thrice a week, adjusted
according to the extent of the lesions, but the dosage given should not exceed 100 mg/ session
(2 mL). The solution is injected into the central aspect of scar tissue, until slight blanching is
clinically visible, usually 0.05 cc or less/injection site, approximately 1 cm apart. 1 5-FU dosage
should be adjusted in patients with liver dysfunction. 14 Contraindications to 5-FU include
pregnancy, breastfeeding allergy,bonemarrowdepression,andsevere intercurrent infection. 1,15
The most common side effects of 5-FU injection include pain or discomfort, ulceration, burning
sensations, and hyperpigmentation at the injection site.1,7,15 Addition of 0.1 ml of TA (40 mg/ml)
to 0.9 ml of 5-FU (50 mg/ml) helps to reduce the pain and also the inflammation. 3

Intralesional 5-FU works by inhibiting fibroblast proliferation, interrupting both DNA and RNA
synthesis as well as inhibiting TGF- β-induced expression of the type I collagen gene in human
fibroblasts.3,5,14 5-fluorouracil acts as an alternative therapeutic agent for

Khan et al.6 has compared the use of TA injection as a monotherapy to TA and 5-FU injection
combination for 150 patients with keloid and hypertrophic scars, who were divided into two
experimental groups. In this study, eight injections were given in weekly

Fig. 4 Keloid Lesions on the Fifth Intralesional Injection. a) 13 x 2.5 x 0.4 cm. b) 3 x 2.5 x
0.1 cm. c) 4 x 2.2 x 0.2 cm. Patient Admitted Improvements as Flattening and Size
Reduction of the Lesions

International Journal of Integrated Health Sciences. 2017;5(1):36–41 39

Triamcinolone Acetonide and 5-Fluorouracil Intralesional Combination Injection in Keloid

Treatment
interval. The group receiving combination of 4 mg TA and 45 mg 5-FU, demonstrated good
results (lesion height reduction: 50–75%) and excellent results (lesion height reduction: 75–
100%) in 63 patients (84%) while in the group receiving 10 mg TA injection as monotherapy,
good and excellent results were seen in 51 patients (68%).

sites may be observed soon after the first 2–3 injection sessions and may heal with the use of
topical antibiotics.2 The hyperpigmentation typically resolves spontaneously after three
months.15 In this case, ulceration developed after the first injection and could be managed with
topical application of gentamycin 0.1 % cream, twice a day.

According to this patient’s history, physical, and laboratory examination, she had no
contraindication towards 5-FU administration and did not need any dosage adjustment. Patient
was given 4 mg TA and 45 mg 5-FU injection combination therapy once a week. Lidocaine
injection was given before therapy administration to minimize the pain. Every injection was
separated by 1 cm distance. Gentamycin 0.1% cream was applied after the procedure and
patient was requested to apply it twice a day if ulceration developed.

Response of therapy commonly needs five to ten injection sessions. The first subjective
symptoms of response are decreased pain and pruritus followed by softened and flattened scar
and decreased erythema.4 In this case, the patient felt symptom improvements as decreased
pruritus and softened keloid lesion after two injections. On examination, keloid on her neck
become flattened and the other on shoulder reduced in size. After five injection series, lesion on
the neck looked more flat and lesion on chest was minimized (Fig. 2–6).

The superficial ulcerations at the injection

References

emerging treatment strategies. Mol Med.

1. Pratchyapruit W, Vashrangsi N. A new therapeutic modality intralesional 5-fluorouracil in the

treatment of keloids and hypertrophic scar. Inst Dermatol Ass. 2012;13(9):157–63.

2011;17(1):113–25.
8. Gauglitz GG. Management of keloids and

2. Kelly AP. Update on the management of keloids. Semin Cutan Med Surg. 2009;28(2):71–6.

hypertrophic scars:current and emerging options. Clin Cosmet Investig Dermatol. 2013;6(1):103-14.

3. Sharma S, Bassi R, Gupta A. Treatment of small keloids with intralesional 5-fluorouracil alone vs
intralesional triamcinolone acetonide with 5-fluorouracil. J Pak Assoc Dermatol. 2012;22(1):35–40.

9. Chike-Obi CJ, Cole PD, Brissett AE. Keloids: Pathogenesis, clinical features, and management. Semin
Plast Surg. 2009;23(3):178–84.

4. Guimarã es CO, Parada MB, Bagatin E. Keloid treatment:comparative intralesional injections of 5-

fluorouracil, corticosteroid and 5-fluorouracil combined with corticosteroid. Surg Cosmet Dermatol.
2011;3(1):60–2.

10. Vivas AC, Tang JC, Maderal AD, Viera MH. Hypertrophic scars and keloids, part 1:conventional
treatments. Cosmet Dermatol. 2012;25(3):309–16.
5. Wolfram D, Tzankov A, Pulzi P, Piza-Katzer H. Hypertrophic scars and keloids-A review of their
pathophysiology, risk factors, and therapeutic management. Dermatol Surg. 2009;35(2):171–81.

12. Dong X, Mao S, Wen H. Upregulation of proinfammatory genes in skin lesions may be the cause of
keloid formation. Biomed Rep. 2013;1(6):833–6.

6. Khan MA, Bashir MM, Khan FA. Intralesional triamcinolone alone and in combination with 5-
fluorouracil for the treatment of keloid and hypertrophic scars. J Pak Med Assoc. 2014;64(9):1003–7.

13. Gupta S, Sharma VK. Standard guidelines of care: keloids and hypertrophic scars. Indian J Dermatol
Venereol Leprol. 2011;77(1):94-100.

7. Gauglitz GG, Korting HC, Pavicic T, Ruzicka T, Jeschke MG. Hypertrophic scarring and keloids:
Pathomechanisms and current and

14. Darougheh A, Asilian A, Shariati F. Intralesional triamcinolone alone or in combination with 5-

fluorouracil for the treatment of keloid and hypertrophic scars. Clin Exp Dermatol. 2009;34(1):219–23.

15. Kranendonk S, Obagi S. An algorithmic approach 40 International Journal of Integrated Health Sciences.
2017;5(1):36–41

11. Edriss AS, Smrcka V. Therapy of keloid and hypertrophic scars:a review. Eur J Plast Surg.
2011;34(5):425–36.

Jono Hadi Agusni, Eva Krishna Sutedja, et al.

Kartamihardja AHS. Comparison of the effectiveness of phosphorus 32 application and 10 mg/cc

triamcinolone acetonide intralesional injection on keloid. IJIHS. 2016;4(1):26–31.

tohypertrophicscarsandkeloids:maximizing nonsurgical options. J Cosmet Dermatol. 2011;24(1):28–39.

16. Indrayati H, Agusni JH, Soedarwoto A,

is more striking in darkly pigmented skin. In Caucasians, IGH may favor those with brown eyes and
brown hair. An apparent female pre- dominance is probably the result of heightened perception of
a cosmetic problem.

98
The typical IGH lesion is a circumscribed, sharply deined, asymp- tomatic porcelain white macule .
The lesions are usually 0.5–6 mm in diameter and often delineated by the skin furrows;
occasionally, lesions are up to 2.5 cm in size (Fig. 66.31). Once present, they do not change in size
or coalesce; their surface is smooth but not atrophic. Spontaneous repigmentation has not been
reported. Hairs within the lesions usually retain their pigment. In most patients, there are multi- ple
lesions on the extensor forearms and shins; the remainder of the extremities can be affected, but
rarely the face.

The most consistent histologic features of IGH are a lattening of the dermal–epidermal junction,
moderate to marked reduction or focal absence of melanin granules in the basal and suprabasal
layers, and a basket-weave hyperkeratosis. There is a moderate to relatively marked reduction in
the number of DOPA-positive epidermal melanocytes (10–50% compared with normal skin), but
these cells are never totally absent. At the ultrastructural level, some melanocytes have normal
melanogenic activity, while others lack mature melanosomes. The

1045
66

Vitiligo and Other Disorders of Hypopigmentation

SECTION

10
Fig. 66.34 Progressive macular hypomelanosis. Note the coalescence
of the non-scaly hypopigmented macules on the center of the back.

DISORDERS ASSOCIATED WITH PREMATURE GRAYING OF

SCALP HAIR
• Piebaldism
• Waardenburg syndrome
• Vitiligo
• Sudden whitening of hair
• Hereditary premature canities
• “Bird-headed”dwarism
• Progeria
• Werner syndrome
• Ataxia telangiectasia
• Rothmund–Thomson syndrome
• Fisch syndrome
• Myotonic dystrophy
• Prolidase deiciency (also in Table 66.11) • Oasthouse disease
1046

Fig. 66.32 Disseminated hypopigmented keratoses. Over 200 guttate minimally elevated
hypopigmented papules developed after several months of

PUVA therapy. Histologically, there was no evidence of verruca plana. Courtesy, Jean L Bolognia, MD

Fig. 66.33 Clear cell papulosis. Multiple hypopigmented, barely elevated lat-topped papules
and macules in the suprapubic area and on the abdomen along the “milk lines” in a 2-year-old boy.
Histologically , these lesions are characterized by large clear cells in the lower epidermis that have
a pattern of immunohistochemical staining similar to clear cells of Toker and extramammary
Paget’s disease. Courtesy, Julie V Schafer, MD.

keratinocytes show marked variation in their content of melanin, which may be absent or markedly
decreased.

The diagnosis of IGH is usually made clinically; the differential diagnosis of guttate leukoderma is
shown in Table 66.7 and includes achromic verrucae plana, pityriasis lichenoides chronica,
disseminated hypopigmented keratoses that follow PUVA therapy (Fig. 66.32) and clear cell
papulosis (Fig. 66.33). Although lesions of atrophie blanche favor the distal shins and ankles, these
porcelain white scars are usually depressed and encircled by papular telangiectasias. The cause of
IGH is unknown, but sun exposure probably plays a role.

Cryotherapy with liquid nitrogen has been described as a possible therapy for IGH. As sunlight is
most likely a precipitating factor, use of sunscreens and physical barriers should be recommended.

Vagabond’s Leukomelanoderma
This skin disorder occurs in older persons in whom dietary deiciency is combined with lack of
cleanliness and heavy infestation with

Table 66.10 Disorders associated with premature graying of scalp hair.

Pediculus humanus var. corporis. These patients have small macules of hypomelanosis (related to
scratching) superimposed on a background of diffuse hypermelanosis, especially of the wrists,
axillae, groin, inner thighs and posterior neck.
Progressive Macular Hypomelanosis
Progressive macular hypomelanosis (PMH) is a fairly common skin disorder, observed more
frequently in young women with darkly pig- mented skin who originate from or reside in tropical
climates. The disorder is characterized by poorly deined, nummular, non-scaly hypopigmented
macules and small patches on the trunk, with rare extension onto the proximal extremities or head
99
and neck region; con- luence of lesions may occur centrally (Fig. 66.34) . Another variant of PMH
features large circular lesions. There is no associated pruritus or preceding inlammation, and
patients are sometimes misdiagnosed as having residual hypopigmentation related to pityriasis
versicolor. Histologically, there is decreased pigment in the epidermis and a normal-appearing
dermis. Electron microscopy demonstrates a shift from large melanosomes in uninvolved skin to
small aggregated membrane-bound melanosomes in hypopigmented skin. Propionibac- terium
acnes residing within hair follicles may play a role in PMH. One proposed treatment regimen
consists of topical 1% clindamycin and 5% benzoyl peroxide plus UVA irradiation (three times per
week for 12 weeks).

Hair Hypomelanosis
Poliosis refers to a circumscribed hypomelanosis of hair (see Table 66.4), whereas canities implies
a more generalized depigmentation of hair. Graying of hair, localized or generalized, is
characterized by an admixture of normally pigmented, hypomelanotic and amelanotic hairs.
Whitening of hair is the endpoint of canities and graying of hair. The graying and whitening of
100,101
human hair that occurs with aging is due to defective maintenance of melanocyte stem cells .

A number of genetic disorders are associated with premature graying of hair (Table 66.10), while
there are both hereditary and acquired causes of diffuse hypomelanosis of hair (Table 66.11). In
Chédiak- Higashi, Griscelli and Elejalde syndromes, the scalp hairs have a silvery hue due to
pigment clumping.

PIGMENTARY DISORDERS

CHAPTER

DISORDERS ASSOCIATED WITH DIFFUSE HYPOMELANOSIS OF SCALP HAIR

 Fanconi syndrome
 Book syndrome
 Down syndrome
 Hallerman–Streif syndrome
 Treacher–Collins syndrome
 Prolidase deiciency (also in Table 66.10)
 Hyperthyroidism
 Chronic protein loss or deiciency (e.g. due to kwashiorkor, nephrosis, ulcerative colitis,
malabsorption)
 Vitamin B12 deiciency
 Tyrosine kinase inhibitors
 Antimalarials (chloroquine > hydroxychloroquine)

Table 66.11 Disorders associated with difuse hypomelanosis of scalp hair. See also Figure
66.11.

Leukodermas without Hypomelanosis

Woronof’s ring

Woronoff’s ring is a blanched halo of fairly uniform width surrounding psoriatic lesions after
phototherapy or topical treatments. There is an element of vasoconstriction, but it is uncertain
whether there is any decrease in pigmentation.
Nevus anemicus

Nevus anemicus (see Ch. 106) presents as a pale area of variable size (often 3–6 cm) with an
irregular, “broken up” outline. It is usually unilateral and located on the trunk. Present since birth,
the lesion is most commonly detected later in life, and it is most noticeable when there is
surrounding vasodilation due to heat or emotional stress. On diascopy, the lesion becomes
indistinguishable from surrounding skin. Histologically, there are no abnormalities in the
melanocytes or melanin content. Nevus anemicus is caused by decreased blood low through the
capillaries in the dermal papillae, due to a localized hypersensitivity of the blood vessels to
catecholamines.

Cutaneous edema and anemia

Cutaneous edema and anemia also produce lightening of the skin and mucous membranes. In the
case of anemia, it is due to decreased hemoglobin levels in the skin.

Angiospastic macules (Bier spots)

Pale macules, usually 3–6 mm in diameter, are seen on the extremities (often more noticeable on
the legs) (see Ch. 106). They are due to local- ized vasoconstriction and are seen most often in
young women. Their appearance may be induced by a dependent position or placing a tour- niquet
on the limb.

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