A Study of Correlation Between Clinical and Histopathological Findings of Erythroderma in North Bengal Population.

BACKGROUND: Erythroderma is a reaction pattern characterized by erythema and desquamation of 90% or more body surface area along with some metabolic alterations.
MATERIALS AND METHODS: Here we studied 32 patients of erythroderma at of North Bengal Medical College for a period of 1 year to find the etiology, clinical features and histological changes. Detailed history was taken from all the patients followed by relevant biochemical investigations and histological examination. To correlate the clinical and histopathological findings chi square test was used.
RESULTS: Male preponderance was present and most of them were in the 4(th) or 5(th) decade. Etiologically the patients were divided into secondary erythroderma developing over pre-existing dermatoses, and idiopathic erythroderma. Secondary erythroderma (n = 24) cases outnumbered the idiopathic cases (n = 8). Among the pre-existing dermatoses, psoriasis was found to be the most common etiologic agent. Apart from erythema the other common presenting features were scaling and itching. Histopathological categorization was possible in 59.3% cases, rest of the cases showed non-specific dermatitis. The most common histopathologic diagnosis was psoriasis (21.8% of cases).
CONCLUSIONS: Our study of clinicopathological correlation of erythroderma patients among north bengal population corroborates with most of the previous studies done in other areas. As ours is a cross-sectional study in a undefined population so we could not determine the true incidence of erythroderma in north bengal population. We might have missed lymphoma as a cause of erythroderma in idiopathic cases due to lack of long follow-up, so we understand that further studies over a defined population with long follow-up is needed to determine the true incidence and causes of idiopathic erythroderma.

What was known?

Erythroderma is a reaction pattern characterized by erythema and desquamation of 90% or more body surface area along with some metabolic alterations. It mostly occurs secondary to psoriasis but can be primary also. As it is a serious disease and the treatment is mainly based on the etiology, diagnosing the cause is very important which relies mostly on histopathology.

Introduction

Erythroderma, first described by Hebra in 1868, is a reaction pattern characterized by generalized and confluent erythema with desquamation affecting more than 90% of body surface area [Figure 1a and 1b] and is usually accompanied by other systemic manifestations resulting in hemodynamic and metabolic derangements.[1234]

Figure 1

(a) Erythroderma (psoriatic). (b) Erythroderma (non-specific)

Erythroderma is the result of a dramatic increase in the epidermal turnover rate. In patients with this disorder, the mitotic rate and the absolute number of germinative skin cells are higher than normal. Moreover, the time necessary for cells to mature and travel through the epidermis is decreased. This compressed maturation process results in an overall greater loss of epidermal material, which is manifested clinically as severe scaling and shedding.

Exfoliative dermatitis accounts for about 1% of all hospital admissions for dermatologic conditions.[3] Overall incidence is 1 to 2 patients per 100,000 populations.[5] In Indian subcontinent, one large prospective study has shown that overall incidence of erythroderma is 35 per 100,000 dermatological patients.[6]

Primary erythroderma develops in normal skin and etiological factors are drug reactions, lymphomas and hematological malignancies or may be idiopathic (25%).[78] On the other hand, secondary erythroderma develops through generalization of existing dermatoses such as eczema, psoriasis, pityriasis rubra pilaris, lichen planus, etc.[7]

Since erythroderma is a serious disease due to its ability to cause metabolic derangement, optimal therapy is very important, which again depends upon the establishment of the causes.[9]

Laboratory findings are typically unhelpful in establishing etiology of erythroderma.[10] A skin biopsy is the only relevant investigation as the histopathological features of the underlying disorders are recognizable in more than half of the cases.[1112] A comprehensive clinicopathological correlation is of substantial importance to render the diagnosis of the cause.[13]

Etiological factors depend largely on the population studied, though clinical presentations may essentially be the same.[14] As no earlier published study was found even after diligent search regarding frequency of underlying causes of erythroderma in North Bengal population, this study might be helpful to asses any variation in clinical, etiological and histopathological profiles among these patients.

The aims of the study were to do histopathological categorization of clinically diagnosed erythroderma patients among North Bengal population and to observe correlation between clinical and histopathological diagnosis.

Materials and Methods

Clinically diagnosed cases of erythroderma attending OPD and IPD of dermatology and medicine department of North Bengal Medical College for a period of 1 year were evaluated by detailed history taking and clinical examinations after informed consent. All the findings were recorded in case data sheet. All required biochemical tests were performed. HIV screening was done in all patients. Radiological tests like X-ray, echocardiography and ultrasonography were performed wherever indicated. A punch biopsy was done under sterile environment for histological examination. Data were analyzed using standard statistical tools. Patients with bleeding disorders (contraindicated for punch biopsy) and seriously ill moribund patients were excluded from the study due to non-availability of informed consent. Ethical approval was taken from the Institutional Ethics Committee.

Correlation of clinical diagnosis with histological findings was thoroughly studied. Data were analyzed using standard statistical tools.

Results and Analysis

Most of the erythroderma patients were in the age group of 4th and 5th decades (31.25% each, n = 10) [Table 1]. The minimum age of the patient with clinical presentation of erythroderma was 16 years and the maximum age was 69 years with a mean age of 41.81 years and median value was 42 years. The ratio between male and female in this study was 1.66:1.

Table 1

Age wise distribution of erythroderma cases with different clinical etiologies

Psoriatic erythroderma was more common in 4th and 5th decades of life [Table 1]. Seborrheic dermatitis as a cause of erythroderma was seen in the age group of 3rd and 4th decade. Erythroderma due to atopic dermatitis was seen in younger populations (before 5th decade of life). Idiopathic erythroderma cases seen in this study were in the age group of 5th and 6th decades of life.

The majority (68.75%, n = 22) of erythroderma cases had chronic onset whereas 31.25% (n = 10) cases had acute onset. Out of 20 erythroderma cases due to pre-existing dermatoses, 17 cases (85%) presented with chronic onset. All 4 cases with drug-induced erythroderma presented with acute onset, whereas 37.5% (3 out of 8) cases with idiopathic erythroderma presented with acute onset and remaining 62.5% cases presented with chronic onset. Cases with more than 6 weeks of duration were considered as chronic erythroderma as an operational definition.

Apart from erythema and scaling which was seen in all erythroderma patients, itching was found in 22 (68.7%) out of 32 cases [Table 2]. Nail changes were evident only in cases secondary to psoriasis, with 7 (63.6%) out of 11 cases of psoriasis presented with nail changes. Eight (25%) cases presented with hair changes including crusting within hair shaft and alopecia, among whom five cases were psoriatic erythroderma and three cases were erythroderma secondary to seborrheic dermatitis. 34.3% of cases (11 out of 32) presented with oozing from the skin surfaces. Mucosal lesions were seen in 9.3% of cases. Four (12.5%) cases of erythroderma presented with dermopathic lymphadenopathy.

Table 2

Correlation of clinical features and etiological types

Fifteen cases (46.8%) presented with systemic complications, most commonly associated with psoriasis [Table 2], while three out of eight patients of idiopathic erythroderma had systemic complications. The most common systemic complain was fever. Other than fever we also found tachycardia, pedal edema, anemia, chilly sensation and weight loss. This difference was statistically significant (P = 0.048, i.e. <0.05). Drug-induced erythroderma cases and erythroderma due to contact dermatitis cases were not associated with systemic complications in our series.

Histopathology was done in all 32 cases to find out the underlying etiology, but histopathological diagnoses was possible only in 19 cases out of 32 cases (59.37%) [Table 3]. Remaining 40.63% cases were diagnosed as non-specific dermatitis. About 21.87% of total cases and 63.63% of clinically diagnosed erythrodermic psoriasis cases were histopathologically diagnosed as psoriasis [Figure 2].

Table 3

Comparison between clinical diagnosis and histopathological diagnosis

Figure 2

Photomicrograph showing psoriatic erythroderma (H and E, ×100)

6.25% of total cases and 66.66% of clinically diagnosed erythroderma cases secondary to seborrheic dermatitis were confirmed as seborrheic dermatitis by histopathology. Subacute spongiotic dermatitis, chronic spongiotic dermatitis and lichenoid dermatitis each comprised of 9.36% of total cases.

Out of four cases clinically diagnosed as erythroderma due to atopic dermatitis two (50%) cases were histopathologically diagnosed as subacute spongiotic dermatitis [Figure 3], one (25%) as chronic spongiotic dermatitis and another (25%) as non-specific dermatitis. Out of two cases of erythroderma clinically suspected due to contact dermatitis, one case (50%) was diagnosed histopathologically as subacute spongiotic dermatitis and remaining one as non-specific dermatitis. Seventy-five percent of drug-induced erythroderma cases were diagnosed as lichenoid dermatitis [Figure 4] and 25% cases were diagnosed as non-specific dermatitis [Figure 5].

Figure 3

Photomicrograph showing subacute spongiotic dermatitis (H and E, ×400)

Figure 4

Photomicrograph showing non-specific dermatitis (H and E, ×40)

Figure 5

Photomicrograph showing lichenoid dermatitis (H andE, ×400)

Among the idiopathic erythroderma cases, histopathological diagnosis was made as acute spongiotic dermatitis in one (12.5%)) case, chronic spongiotic dermatitis in another cases and non-specific dermatitis in remaining six (75%) cases.

Histologically [Table 4] acanthosis was the most common feature found in 87.5% (28 out of 32) cases, followed by parakeratosis and mixed cellular infiltrates in dermis, 62.5% (20 out of 32 cases) each. Hyperkeratosis was seen in 53.12% (17 out of 32) cases, spongiosis in 31.25% (10 out of 32 cases).

Table 4

Histopathological features seen in different erythroderma cases

Parakeratosis and acanthosis were present in all (100%) histopathologically diagnosed cases of psoriatic erythroderma (n = 7). Hypo/absent granulosis and spongiotic vessels in dermis seen in 85.71% (six out of seven) histopathologically diagnosed psoriatic erythroderma cases. Supra papillary thinning, Munro's microabscesses and spongiform pustules of Kogoz were seen in 57.14% of cases each.

Mixed inflammatory cell infiltration was seen in all cases of non-specific dermatitis, followed in a decreasing order by acanthosis (76.92% cases), hyperkeratosis (61.53%), dermal edema (53.84%) and parakeratosis (46.15%) [Table 5].

Table 5

Histopathological features seen in non-specific dermatitis in the study population (n=13)

Discussion

Erythroderma can develop over pre-existing dermatoses, as a drug reaction, as a manifestation of malignancy or systemic diseases. In a fair number of cases no etiology is found.[15] There are some congenital causes of erythroderma as well – bullous congenital ichthyosiform erythroderma (autosomal dominant) and congenital ichthyosiform erythroderma (autosomal recessive).[16]

In daily practice diagnosis of erythroderma usually revolves around the history of pre-existing dermatosis but on many occasions there was no such history and then it becomes a diagnostic challenge to find out the cause. The clinical features of erythroderma are non-specific with erythema and scaling along with pruritus are the main presenting features. So a comprehensive clinicopathological correlation is of substantial importance to render the diagnosis of the cause.[13]

The present study was done for histopathological categorization of clinically diagnosed erythroderma patients and to observe correlation between clinical and histopathological diagnosis. Chi square test was used to find the clinical and histological correlation. The p-value was 0.968928. The result was not significant at P <0.05.

The mean age of the patients with erythroderma was found to be 41.81 years in this study group, with a range of minimum 16 years to maximum 69 years. The median age of the study group was 42 years which corroborates with the previous published studies.[171819] The male and female ratio in the present study was 1.66:1 and also matches the previous studies.[181920]

In our study, apart from erythema and scaling which was present in all cases, the most common presenting feature was itching (68.7%). Hair changes were seen in 25% of erythroderma patients and nail changes ranging from onycholysis, subungual hyperkeratosis and shiny nails were evident in 21.8% cases. Dermatopathic lymphadenopathy was seen in 12.5% cases. Moreover, 46.8% cases had systemic complications like fever, tachycardia, pedal edema, anemia and weight loss. Most of the patients with secondary complications were psoriatic erythroderma cases.

A majority of the presenting symptoms were corroborating with the findings described in studies done previously.[1721] In one study by Pal et al., shiny nails and Beau's lines were most common nail changes.[20]

Most of the previously published studies showed that erythroderma mostly occurs on pre-existing dermatoses (minimum 50% to maximum 74.4%). The comparisons of the different etiologies of erythroderma in previous studies are given in Table 6.[61718192022232425] Drug-induced erythroderma were seen in 5% to 29.4% of total cases, idiopathic erythroderma cases were seen in 6.5% to 29.2% of cases, and malignancies were found to be the underlying cause in a maximum of 12.5% cases. However, in our study we did not find any case of erythroderma having any underlying malignancy as a cause. Studies by Mittal et al.[26] and Sehgal et al.[25] also did not found any case of malignancy-associated erythroderma. It may be a fact that the idiopathic cases of erythroderma diagnosed in our study might have been diagnosed as neoplastic erythroderma if proper and long follow up could be instituted as cutaneous lymphoid neoplasia may present with erythroderma as a sole clinical feature so long-term follow up with repeated skin biopsies is needed to establish underlying malignancy as a cause of erythroderma.

Table 6

Etiology of erythroderma (exfoliative dermatitis) cases in different previous studies

Among the pre-existing dermatoses, we found psoriasis as the most common (34.3%, n = 32) etiology in our study corroborating previous studies.[17192026] In the drug-induced group, drugs like phenytoin, sulphonamide, dapsone and NSAIDs were responsible for causing erythroderma in our study. Interestingly we did not find any case of carbamazepine-induced erythroderma in our study which is in an unusual finding as per previous studies.[1727] King et al.[14] and Sigurdsson et al.[19] also found carbamazepine as a less common cause of drug-induced erythroderma in their studies. Similarly, we did not found any case of allopurinol-induced erythroderma. The cause may be less frequency of prescription of these drugs in North Bengal or less genetic susceptibility of the studied population but as in our study there were only four cases of drug-induced erythroderma which is very less to draw any conclusion.

We found that majority (68.75%, n = 22) of erythroderma cases had chronic onset, whereas 31.25% (n = 10) cases had acute onset. As there is no available standard demarcation of chronic and acute onset erythroderma, we considered the cases with clinical features started in preceding 6 weeks as acute onset erythroderma. All the four cases of drug-induced erythroderma had acute onset which is in accordance with previous studies.[1025]

Interestingly we did not found any case of erythroderma associated with HIV as there is increased chance of erythroderma either due to the drugs used HAART or exaggeration of certain dermatosis in HIV positive individuals but studies by Pal et al. and Akhyani et al. also showed similar results. Morar et al. in their study found HIV positive in many of their cases and they concluded that erythroderma can be a marker of HIV in young black males.[28]

In our study, histopathological diagnosis was most consistent with clinical diagnosis in drug-induced erythroderma (75%) cases. Histopathological findings were consistent in 66.66% of seborrheic dermatitis cases and 63.63% of psoriatic erythroderma cases.

The study conducted by Akhyani et al. showed that histology was helpful to correlate clinical diagnosis in 50% of cases. They found psoriasis to be the predominant etiologic agent causing erythroderma.[17] According to Jowker et al., there was clinicopathological correlation of erythroderma in 66.4% of cases and subacute and chronic dermatitis was the most common histopathological finding (35.18%), followed by drug reaction (16.66%) and psoriasis (14.81%). Most consistent histopathology was seen in drug reaction cases followed by psoriasis.[18] In their study of 20 erythroderma cases, Sudho et al. also found that 36% cases were psoriasis, 24% cases were dermatitis and 8% each were erythema multiforme and pemphigus foliaceus.[27]

Over all prognoses was good in our study with drug-induced cases responded very well to treatment and we did not came across any death in our study thus supporting that prognosis of erythroderma is good.[17] However, the mortality rate is shown to be up to 64% in a study by Sehgal et al.[25]

Conclusion

In our study, secondary erythroderma (n = 24) cases outnumbered the idiopathic cases (n = 8) with psoriasis being the most common cause of secondary erythroderma followed by drugs. Histopathological categorization was possible in 59.3% cases, and the remaining cases showed non-specific dermatitis. Most common histopathologic diagnosis was psoriasis (21.8% of cases). We recognized two limitations of our study. True incidence of erythroderma in North Bengal population could not be determined as this was a cross-sectional study and no defined population group was available. Moreover, we might have missed the cases of erythroderma secondary to the cutaneous lymphoma group due to lack of follow-up studies.

What is new?

No known study of erythroderma patients are there in north bengal population and this is the first attempt to study the clinocopathological correlation among them.