Nail changes in immuno-bullous disorders: A cross-sectional study

   Abstract 


Context: Autoimmune blistering (AIBD) disorders affect mucosae, skin, and appendages. Appendageal involvement has not been studied extensively to date. However, they are important as nail changes are commonly encountered during a flare-up of the disease. Aims: To determine the prevalence and patterns of nail changes in various Immunobullous disorders and to study the relationship between the nail changes and the disease duration and severity. Settings and Design: A cross-sectional study was conducted at the Department of Dermatology, venerology, and leprosy at a tertiary care center in Mumbai. Materials and Methods: A cross-sectional study including a total of 74 cases of Immunobullous diseases was conducted and the prevalence of nail changes was determined. The association between the mean number of nail changes and the disease duration and severity was analyzed using ANOVA (Analysis of variance) and unpaired t-test. Statistical Analysis: The Statistical Package for Social Studies (SPSS) software was used for statistical evaluation. Results: We found that the prevalence of nail changes was 91%. There was a significant difference in the mean number of nail changes with respect to the severity grades of mucosal involvement in AIBD (P value < 0.05). There was no significant difference in the mean number of nail changes with respect to the severity grades of Pemphigus vulgaris (PV), Pemphigus foliaceous (PF), subepidermal blistering diseases, and the duration of AIBD. Conclusions: Nails are frequently affected in AIBD. The number of nail changes is related to the severity of mucosal disease but not to duration.

Keywords: Nail changes, pemphigoid, pemphigus


How to cite this article:
Kadu PP, Kura MM. Nail changes in immuno-bullous disorders: A cross-sectional study. Indian J Dermatol 2023;68:233
   Introduction Top

The reported prevalence of nail changes in autoimmune blistering diseases (AIBD) ranges from 31-72% according to various studies.[1],[2] Antibodies against the nail unit antigens expressed in the nail matrix,[1] hyponychium,[1] and the proximal nail fold[1] and extension of periungual bullae[1],[3] form the basis of the pathogenesis of nail changes. The nail changes may be associated with severe mucocutaneous disease and duration.[1],[3] Nail changes are more commonly described in fingernails than toenails. We intend to study the various nail changes in AIBD and determine their association with the disease severity and duration.

   Materials and Methods Top

This was a cross-sectional study at a tertiary care center in Mumbai from October 2018-February 2021 in the Department of Dermatology, Venerology, and Leprosy. A total of 74 cases of AIBD were enrolled in the study after obtaining informed consent and ethical clearance. Inclusion criteria were all the cases clinically suspected of having AIBD and diagnosed using confirmatory tests such as histopathology, direct immunofluorescence, and ELISA (Enzyme-linked immunosorbent assay). The exclusion criterion was those not consenting to the participation in the study. A detailed history was taken to determine the age of onset, duration, and evolution of the disease, oral, and genital involvement, and the presence of nail changes. A complete dermatological examination was performed. The lesions were assessed with the grading system based on the body surface area (BSA) as mild (<20% BSA) or severe (>20% BSA) for subepidermal blistering diseases and as per Pemphigus Disease Area Index (PDAI) for pemphigus group of diseases.[1] Mucosal lesions were graded using the PDAI as mild (score <15), moderate (score 15-45), or severe (score >45)[1] for the pemphigus group of diseases as well as for subepidermal blistering diseases. After a thorough examination, all the patients were subjected to histopathological, serological, and immunofluorescence studies and were classified into pemphigus and pemphigoid groups of diseases.

Nail changes in the study subjects were evaluated independently by two experienced dermatologists. Involvement of the nail was noted whether present or absent. The pattern of involvement in each nail was studied and the total number of nails showing various patterns was summated to get the total number of nail changes in each patient. Additional investigations like pus culture and sensitivity, potassium hydroxide (KOH) mount, and fungal culture were performed where required.

The various nail changes were diagnosed and documented based on thorough clinical evaluation and investigations. This data was recorded in pre-structured case record formats. Photographic documentation of mucocutaneous lesions and nails was done after obtaining informed consent.

The categorical variables were expressed in the form of numbers and percentages. The quantitative data were summarized as mean with standard deviation. The mean number of nail changes was calculated with respect to severity grades (mild, moderate, and severe) of the pemphigus group of diseases and mucosal severity grades (mild, moderate, and severe) of all the AIBD and compared using the Analysis of Variance (ANOVA) test. The mean number of nail changes was calculated with respect to severity (mild and severe) grades of pemphigoid diseases and compared using the unpaired t-test. The mean number of nail changes was calculated with respect to the duration (≤2 years and >2 years) of AIBD and compared using the unpaired t-test. The Statistical Package for Social Studies (SPSS) software was used for statistical analysis.

   Results Top

The characteristics of the study population are given in [Table 1].

Of the total number of 74 cases of AIBD encountered in the study period, 67 (91%) had nail changes. Toenail involvement was seen more commonly than fingernail involvement, and the commonest nail involved was the great toe. Thirty-nine out of 74 cases (53%) reported nail changes appearing after the onset of AIBD. Nail findings with an associated flare of the disease were seen in ten cases (15%) with paronychia, anonychia, onychomadesis, and periungual bulla being the changes present during an acute exacerbation.

The various nail changes in the order of frequency are given in [Figure 1].

There was a significant difference in the mean number of nail changes with respect to the severity grades of mucosal involvement (mild, moderate, severe) in AIBD (P value <0.05) [Table 2].

Table 2: Association of the mean number of nail changes among different severity grades of mucosal disease in all cases of AIBD

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There was no significant difference in the mean number of nail changes with respect to the severity grades of Pemphigus vulgaris (PV) and Pemphigus foliaceous (PF) (PDAI mild, moderate, severe) (P value >0.05) [Table 3].

Table 3: Association of the mean number of nail changes among cases of different severity grades of PV and PF

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In two cases of pemphigus erythematosus (PE), the case with the mild disease had 4 and the case with the moderate disease had 7 nail changes.

There was no significant difference in the mean number of nail changes with respect to the severity grades (BSA mild and severe) of subepidermal blistering diseases. (P value >0.05) [Table 4].

Table 4: Association of the mean number of nail changes in cases of the mild and severe subepidermal diseases

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There was no significant difference in the mean number of nail changes with respect to the duration (≤2 years and >2 years) of AIBD (P value > 0.05) [Table 5].

Table 5: Association of the mean number of nail changes in cases having a disease duration of ≤2 years with >2 years in all the cases of AIBD

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   Discussion Top

Our study showed that nail involvement occurs commonly in the pemphigus and the pemphigoid group. Out of the 67 (91%) cases that had nail involvement, 52 (78%) cases were pemphigus and 15 cases (22%) belonged to the pemphigoid group.

Nail changes have been reported ranging from 31-72% of cases in various studies.[1],[2] However, we found nail changes in 91% of cases. This could be explained by the fact that we included any nail change encountered in these patients that included both changes primarily related to the AIBD as well as other secondary causes.

Toenail involvement was seen more commonly than a fingernail, and the most commonest involved nail was the great toe. The most frequently reported nail findings in the literature are paronychia and onychomadesis.[1] In our study paronychia was the commonest nail finding. Other changes seen in our cohort were onychomycosis, Beau's lines, onychorrhexis, subungual hyperkeratosis, koilonychia, platynychia, leukonychia, habit-tic deformity, pincer nail, discoloration, longitudinal melanonychia, and pterygium [Table 2]. However, few changes reported in the literature like subungual hamorrhage, pitting, and trachyonychia were not seen in our study group.

Paronychia [Figure 2] was seen in 24 (36%) cases in our study affecting fingernails more commonly than toenails. 16 (66%) cases had multiple digital involvements. The most involved digit was the middle finger. 18 (75%) cases were pemphigus (14 PV, two PF, two PE) and six (25%) cases were BP. The most cultured organism in our cohort was methicillin-resistant Staphylococcus aureus (MRSA). One case of relapse of PV presented as acute paronychia of the middle finger with anonychia [Figure 3], indicating the importance of nails as markers of the disease activity. Occupational causes (exposure to irritants, alkalis, prolonged immersion in water) were not considered in our study. It was difficult to distinguish between paronychia primarily due to AIBD or secondary to invasion by organisms in some cases. A few cases had multiple types of nail changes in the same nail unit indicating ongoing disease activity. We propose that when nail changes described in AIBD are seen concurrently in one nail apparatus, the likely primary cause is AIBD rather than other causes such as occupational or infections.

Figure 3: A case of relapse of Pemphigus vulgaris having paronychia and anonychia of the middle finger

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Beau's lines were seen in 20 (30%) of our study cases and out of which 16 (80%) cases were of pemphigus (12 PV, three PF, one PE) and four (20%) cases were pemphigoid. The most commonly involved nail was the great toe. 16 cases (80%) had the involvement of multiple digits. Four cases (20%) had multiple Beau's lines corresponding to the episodes of exacerbation [Figure 4].

In our study, 17 cases (25%) had melanonychia, of which 14 (82%) cases were PV and 3 (18%) cases had Bullous Pemphigoid (BP) [Figure 5]. Fourteen (82%) cases had involvement of multiple digits. The thumbnail and the great toenail were involved with equal frequency. It does not appear to be related to the primary disease process in our study.

In our study, dystrophic changes were seen in 14 (21%) cases. The commonest nail affected by this change was the great toe. Ten (71%) cases belonged to the pemphigus group of diseases (eight PV, two PF) and four (29%) cases had BP.

Onychomadesis was seen in 12 (18%) cases in our study which included eight (67%) cases of pemphigus (seven PV, one PF) and four (33%) cases of BP. The great toe was the most commonest affected digit. Nine cases had multiple digital involvements [Figure 6]. Onychomadesis was frequently associated with paronychia in our study, indicating interruption of the nail matrix activity due to the underlying disease process.

Nail discoloration was seen in 12 (18%) cases in our study. Seven (six PV, one PF) (58%) cases belonged to the pemphigus group while five (42%) belonged to the pemphigoid (BP). The great toenail was the most commonest nail affected. In seven cases, all the fingernails and toenails were affected. Orange, black, yellow, and brown chromonychias were seen. Black chromonychia was seen in a PV case [Figure 7] which occurred following treatment with cyclophosphamide within a month. The likely explanation was that the pigmentation resolved completely after the discontinuation of cyclophosphamide. Other causes of discoloration were henna application, onychomycosis, and age-related changes.

Figure 7: Brown chromonychia in a case of Pemphigus vulgaris receiving cyclophosphamide

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In our study, 11 (16%) cases had subungual hyperkeratosis out of which nine (82%) cases had pemphigus (eight PV, one PE), and two (18%) cases had pemphigoid disease (BP). The most commonly involved nail was the great toe, and five (45%) cases showed symmetrical involvement.

Onychorrhexis was seen in ten cases (15%) in our study. Five cases (50%) had pemphigus (two PV, two PF, two PE) and five (50%) cases were pemphigoid (BP). The most commonly involved site was the great toe. Out of ten cases of onychorrhexis, six were from the geriatric age group (>60 years) [Figure 8] and had onychorrhexis involving either toenail only or both fingernails and toenails.

Platynychia has seen in nine (13%) cases. 89% of cases were PV and only one case (11%) was BP. Koilonychia was found in five cases (7%) in our study. The commonest affected nail was the thumbnail. Only one case in our study had low hemoglobin. This was a new finding in our study that has not been previously reported with AIBD.

Onychomycosis was seen in five (7%) cases, and all of them had pemphigus (four PV, one PF). Distal-lateral subungual and total dystrophic were the morphological variants seen. The thumbnail was most affected. Multiple digits were involved in two cases. A similar study by J. Vélez-Ponce et al. showed these two patterns in their study.[4]

Anonychia was seen in four (6%) cases in our study, out of which three (75%) cases were PV, and one case (25%) BP [Figure 9]. This nail change was attributable to the primary disease process as there were other associated findings like paronychia and periungual bullae but was unrelated to the disease severity.

True leukonychia was seen in three (4%) cases, out of which two had PV and one had Dermatitis herpetiformis (DH). Punctate and partial leukonychia were the variants. The findings were present before the disease onset and were inferred as incidental.

Onycholysis was seen in three (4%) cases and the most commonly involved nail was the great toe. Two cases were PV and one case was PF. All the cases had mild disease as per PDAI. Involvement was symmetrical in two cases involving great toes.

Periungual bullae were seen in three cases (4%) in the study, out of which two cases were PV and one case was BP [Figure 10]. Multiple digits were affected in one case and two cases had the involvement of a single digit. As the cases had associated anonychia and paronychia, these nail changes could be secondary to AIBD.

Pterygium was seen in three cases (4%) in our study including one case of PV and two cases of BP [Figure 11]. This finding was present in two cases even before the onset of the disease and could be due to trauma. However, in one case this finding was reported by the patient to be present after the onset of the disease.

Figure 11: Pterygium with depigmentation of proximal and lateral nail fold in a case of Bullous pemphigoid with Vitiligo vulgaris

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A habit-tic deformity was seen as an incidental finding in one case of PF. Thumbnails are usually affected[5] but in our case, the middle finger was affected due to nail-biting.

One case of PV had a pincer change in all the toes, which was a coincidental finding. Trauma was a possible explanation here as it has not been reported with AIBD.

In our study, nail changes were more frequent in patients with severe mucosal disease as compared to mild mucosal disease [Table 2]. In a study conducted by Baghad et al., nail disease was correlated with severe oral involvement.[6] However, in a study done by Gopal et al., there was no significant association between mucosal involvement with the nail changes.[1] It has been proposed that the autoantibodies against desmoglein 3 (Dsg3) alone may have a role in the development of paronychia in PV.[7] This supports the association of mucosal disease severity with nail changes in PV.

A study conducted by Habibi et al. showed that the number of skin bullae was higher in patients with nail changes indicating that nail changes have some association with the severity of the cutaneous disease.[3] However, we found no significant difference in the number of nail changes in the pemphigus group and the subepidermal group when disease severity (cutaneous and mucosal combined) was taken into consideration [Table 3] and [Table 4]. This could be explained by the fact that most patients were on treatment and skin lesions tend to resolve earlier than mucosal disease and nail changes.

The number of nail changes was not related to the disease duration [Table 5]. A similar finding has been reported in a study by Schlesinger et al. where the disease duration was not related to nail change.[8] This contrasts with findings reported in other literature where nail changes are seen more frequently with longer disease duration.[1],[9] This discrepancy in our study and the literature could be explained by the fact that most of the patients with nail changes were evaluated in the early phase of the disease (at their first consultation). The skin lesions resolve earlier than the nail lesions, as the drug penetrates with difficulty in the nail plate by virtue of its unique anatomy.[10] The nail changes observed in the later stage were perhaps appendageal indicators of active disease.

   Conclusion Top

Nail is a frequently affected site in AIBD and should be examined thoroughly. The number of nail changes is related to the severity of mucosal disease but not to duration. Prompt treatment of cases with the severe mucosal disease may decrease the rate of occurrence of nail disease.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 

   References Top
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[PUBMED]  [Full text]  2.Cahali JB, Kakuda EYS, Santi CG, Maruta CW. Nail manifestations in pemphigus vulgaris. Rev Hosp Clin Fac Med Sao Paulo 2002;57:229-34. Doi: 10.1590/s0041-87812002000500007.  Back to cited text no. 2
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    4.Vélez-Ponce J, Ponce-Olivera RM, Bonifaz A, Araiza-Santibañez J, Tirado-Sánchez A. Species isolated as the cause of onychomycosis in patients with pemphigus vulgaris. Revista Médica del Hospital General de México 2016;79:1-4. DOI: 10.1016/j.hgmx.2015.11.001  Back to cited text no. 4
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    7.Laffitte E, Panizzon RG, Borradori L. Orodigital pemphigus vulgaris: A pathogenic role of anti-desmoglein-3 autoantibodies in pemphigus paronychia? Dermatology 2008;217:337-9. Doi: 10.1159/000155645.  Back to cited text no. 7
    8.Schlesinger N, Katz M, Ingber A. Nail involvement in pemphigus vulgaris. Br J Dermatol 2002;146:836-9. Doi: 10.1046/j.1365-2133.2002.04696.x.  Back to cited text no. 8
    9.Tosti A, André M, Murrell DF. Nail involvement in autoimmune bullous disorders. Dermatol Clin 2011;29:511-3, xi. Doi: 10.1016/j.det.2011.03.006.  Back to cited text no. 9
    10.Grover C, Bansal S. A compendium of intralesional therapies in nail disorders. Indian Dermatol Online J 2018;9:373-82. Doi: 10.4103/idoj.IDOJ_280_18.  Back to cited text no. 10
[PUBMED]  [Full text]  
  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11]
 
 
  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]

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