Clinical predictors of outcome in vitiligo

Introduction

Vitiligo is a common dermatological disorder characterized by milky-white depigmented macules devoid of identifiable melanocytes. [1] Its incidence varies from 1-2% worldwide and has been shown to be as high as 3-4% in India. [2] Studies analyzing the clinical features of progressive vitiligo can help defining clinical parameters at presentation, which could predict the outcome of the disease. There are few studies dealing with this subject till date, especially from the Indian subcontinent. This study was conducted to assess the significance of clinical parameters like family history, site of involvement, clinical signs and type of vitiligo in predicting the progression of vitiligo.

Materials and Methods

A retrospective analysis of 199 consecutive patients presenting to the Dermatology OPD in JIPMER, Pondicherry between July 2000 and July 2001 was done utilizing a standard proforma. Patients already on treatment at presentation and those with disease duration of less than six months were excluded from the study.

Progression was defined as the appearance of new lesions or enlargement of existing lesions in the three months before presentation. Involvement of the face, limbs, trunk and mucosale were recorded separately. After the history and clinical examination, the vitiligo was classified as segmental and nonsegmental. Segmental vitiligo was diagnosed if it followed a dermatomal distribution. Nonsegmental vitiligo was further classified into vitiligo vulgaris, acral/ acrofacial, focal and mucosal vitiligo.

Statistical significance of the results was tested using the students′ t test, the Fisher exact test and the x2 test and interpretations were made at the 5% significance level.

Results

There were 102 men (51. 2%) and 97 women (48. 8%) in the 199 patients enrolled for the study. The clinical features of progressive and non-progressive vitiligo were compared [Table - 1]. Overall, 153 patients (76. 9%) had progressive disease.

A positive family history was elicited in 15 (7. 5%) patients. All of them had progressive disease. Of the 184 patients with a negative family history, 138 (75%) had progressive vitiligo. This association of family history with progression was statistically significant (p=0. 027).

The mean age at presentation was 30. 3 years. The mean age at onset of vitiligo was 26. 6 years, being earlier in those without progression (24. 8 years) than in those with progressive disease (27. 2 years). The mean duration of disease was 3. 5 years; it was 3. 4 years in the progressive disease group as against 4 years in those without disease progression. These differences did not achieve statistical significance.

The sites affected most commonly were the limbs 155 (77. 9%) and the mucosae 118 (59. 3%). The face was involved in 48 (24. 1 %) patients and the trunk in 51(25. 6%) patients. Progressive disease was seen in 82. 2% (97/118) patients with mucosal involvement; 81. 25% (35/48) of patients with involvement of the face; 78. 4% (40/51) and 77. 4% (120/155) patients with trunk and limb involvement respectively. Of these only mucosal involvement achieved statistical significance for disease progression (p=0. 032).

Isomorphic Koebner′s phenomenon (IKP) was seen in 33 (16. 6%) patients, leucotrichia in 86 (43. 2%) and trichrome sign in 132 (66. 3%) patients. Nearly ninety one percent (30/33) patients with IKP had progressive disease, which was statistically significant (p=0. 036). 76. 5% (101/132) patients with trichrome sign and 70. 8% (67/ 86) with leucotrichia had progressive disease but these figures were not significant statistically.

Vitiligo was predominantly nonsegmental (93%, 185/199). Vitiligo vulgaris (96/199) was the commonest type, followed by acral/acrofacial (69/199) and mucosal (20/199). Fourteen patients (7%) had segmental vitiligo and none of them (0%) had progressive disease. Nonsegmental vitiligo showed progression in 82. 7% (153/185) cases. This difference was statistically significant (p=0. 033). Among the types of nonsegmental vitiligo, progression was noted in 95% (19/20) patients with mucosal vitiligo, in 80. 2% (77/96) patients with vitiligo vulgaris and 82. 6% (57/96) in acral/acrofacial vitiligo; the correlation between mucosal vitiligo and progression being statically significant (p=0. 043).

Discussion

Many factors like emotional stress, sunburn and pregnancy have been speculated to be aggravating factors of vitiligo in the existing literature; however objective clinical findings of progressive vitiligo are yet to be elucidated. [3] Inability to define the outcome and progression of the disease often leads to a disappointed and dissatisfied patient who ends up in doctor shopping. Since the progression and response to therapy show considerable inter-patient variability, the greatest challenge facing the physician is to predict the outcome of the disease at the very outset. In the absence of reliable laboratory indicators, it becomes important to recognize certain clinical parameters of vitiligo that can determine disease progression in a given patient. [1],[3],[4] In the present study, we had a female to male ratio of 11: 1 which was in concordance with recent data. [5] However, sex had no bearing on the progression of vitiligo.

In our study, a positive family history was obtained in 15% and notably, there was a statistically significant higher rate of progression of vitiligo in those cases with a positive family history.

Segmental and nonsegmental vitiligo have been postulated to have a different etiopathogen-esis and clinical course by many investigators. [6],[7] Segmental vitiligo ceases to progress after a short period while nonsegmental vitiligo, thought to be of autoimmune origin can progress continuously at a gradual rate throughout life. In our study, nonsegmental vitiligo showed a statistically significant higher rate of progression than segmental vitiligo thus confirming the poorer prognosis of nonsegmental vitiligo. The age at onset of vitiligo and the duration of disease in our cases did not correlate significantly with the progression of the disease. However, those without progression tended to have an earlier age at onset, which could be explained by the fact that segmental vitiligo is associated with an earlier age at onset and shows a more favorable course and limited tendency to progress. [6] Previous studies have concluded that IKP is more common in patients with progressive vitiligo. [3],[8] Our study confirmed this by finding a significantly higher rate of progression in patients showing IKP The presence of leucotrichia has been linked to the poor response to the medical treatment. However, as has been noted by other studies, leucotrichia per se is not related to disease activity. [3] Though, leucotrichia was noted in 43. 2% of our cases but it did not correlate significantly with disease progression.

Trichrome sign (describing a tan coloured zone between the normal skin and the depigmented macules) was seen in 66. 3% of our cases, but was not significantly associated with disease progression. Some studies have suggested that it could represent a form of IKP and may indicate that the disease is in a dynamic phase. [4] However, the exact significance of this sign still remains unclear.

Mucosal involvement in vitiligo is commoner or rather more easily detectable in dark-skinned races than in Caucasians. Lip involvement has been reported by various studies to be ash high as 50%. [9] Investigators have also-noted involvement of genitalia, nipples, buccal mucosa, gingivae and alveolar margins. Nearly sixty percent (118/199) of our patients had mucosal involvement, which was significantly associated with progression. This finding was in concordance with that of Hann et al, [3] which to the best of our knowledge is the only other report, highlighting this association. It would thus be worthwhile to state that mucosal vitiligo is a poor prognostic indicator that portends disease progression.

To conclude, it becomes imperative to individualize each case of vitiligo and identify clinical features that can portend progression at the time of the first interview. The presence of a positive family history, mucosal involvement, the isomorphic Koebner′s phenomenon and nonsegmental vitiligo-specifically, mucosal vitiligo are associated with progressive disease. Predicting progression at the beginning would also enable one to formulate an empirical plan of management, which would be appropriate to the activity of the patients′ disease.