ORIGINAL ARTICLE

Year: 2018 I Volume: 1 I Issue: 3 I Page: 75-79

CLINICOPATHOLOGICAL CORRELATION IN ERYTHRODERMA

Anshul Maheshwari 1, Uma Shankar Agarwal2, Ram Singh Meena2, Saroj Purohit2, Surendra Kumar Thalore3
1
Consultant Dermatologist
2
Professor, Department of dermatology, SMS Medical College & Hospital, Jaipur.
3
Assistant Professor, Department of dermatology, SMS Medical College & Hospital, Jaipur.
Corresponding Author:
Dr. Uma Shankar Agarwal
397, Shree Gopal Nagar, Gopalpura Bypass, Jaipur • Email: [email protected]

Abstract
Background: Erythroderma, or generalized exfoliative dermatitis, is a disease characterized by erythema and scaling involving more
than 90% of the body's surface. Diagnosing erythroderma is easy but finding its cause is difficult. There is a paucity of Indian studies
over the etiology, clinical profile and its histopathological correlation.
Aims and objectives: To assess the demographic profile, clinical features and histopathological correlation in erythroderma patients.
Material and Methods: We registered all patients of erythroderma consecutively from January 2013 to December 2014. After a
thorough history and clinical examination, a provisional clinical diagnosis was made. We performed biopsy from two representative
sites of patient and it was sent for histopathological examination. The slides were examined by three independent observers without any
relevant clinical information. The clinical diagnosis was matched with the blinded microscopical diagnosis.
Results: A total of 66 patients were enrolled in this study. The mean age of the study group was 53.7±16.56 years (Range: 14 to 86 years)
with male outnumbering female in a ratio of 3.4:1. Most common cause of erythroderma noted in the study was eczema of various types
(53.03%), followed by psoriasis (30.30%), drug induced (12.12%), lymphoma (1.515%), mycosis fungoides (1.515%) and idiopathic
(1.515%). Clinico-pathological correlation occured in about 67% (range: 63.6% to 68.2%) of patients (k value 0.495 to 0.572).
Conclusion: Most of the clinical features of erythroderma are overlapping. Specific and diagnostic features of diseases are seen only in
a few patients. Clinico-pathological correlation should be done for better diagnosis of patient. Repeated evaluations, close follow-up
and multiple skin biopsies are recommended for a better clinical diagnosis and patient care.
Key words: erythroderma, clinicopathological correlation, histopathology

Introduction The study was performed to find out the causes of erythroderma
Erythroderma or exfoliative dermatitis is an inflammatory in north-west part of India, to find out the epidemiological,
disorder in which erythema and scaling occur in a generalized clinical profile of these patients and histopathological
distribution involving more than 90% of the body surface.
1 correlation.
Because most patients are elderly and skin involvement is Material and Methods
widespread, the disease implies an important risk to the life of the The study was conducted from January 2013 to December 2014.
patient 2. Hasan and Jansen estimated the annual incidence of All cases of erythroderma attending skin outpatient department
erythroderma to be 1 to 2 per 100,000 patients 3. This disorder were included in the study. A thorough history followed by a
may represent a variety of cutaneous and systemic diseases, and meticulous general, physical and dermatological examination
therefore a thorough workup is essential which include detailed was to form a clinical diagnosis. Laboratory investigations
history of triggering factors like drugs, occupation, sunlight including complete hemogram, blood glucose, blood urea,
exposure, pre-existing dermatoses, infections, malignancies etc. serum creatinine, liver function test, serum electrolytes and chest
It should be followed by a meticulous clinical examination for radiograph were done in all cases. Other relevant investigations
specific diagnostic clues to rule out its etiology. Histopathology including abdominal ultrasound, peripheral blood smear, fine
can help in identifying the cause of erythroderma in up to 50% of needle aspiration cytology (FNAC) of lymph nodes and CT scan
cases, particularly by multiple skin biopsies.4 were done wherever needed. A four millimeter skin punch
Indian studies showed a higher prevalence of erythroderma than biopsy was performed in all patients from two representative
other studies. Sehgal and Srivastava recorded the incidence of sites. The slides were independently analysed by three different
erythroderma from the Indian subcontinent as 35 per 100,000 observers without relevant clinical information. Histopathological
dermatologic outpatients. But there are conflicting views over diagnosis was correlated with clinical diagnosis to make final
role of histopathology as some studies were unrewarding.5 diagnosis.

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 Clinical Features Psoriasis Eczema Drug Induced Lymphoma Mycosis Fungoides Idiopathic Total P Value
Itching 20 35 7 1 1 1 65 0.214
Fever 10 6 4 1 0 0 21 0.059
Shivering 12 10 4 1 0 0 27 0.151
Arthralgia 7 2 0 0 0 0 9 0.047
Edema 9 20 3 1 0 1 34 0.575
Lymphadenopathy 14 22 3 1 1 0 41 0.409
Palmoplantar 10 5 0 0 0 0 15 0.023
Keratoderma
Nail Changes 17 20 1 0 0 0 38 0.005
Pallor 7 10 2 1 0 0 20 0.72

TABLE 1: Clinical Profile of Patients

Results: 63.6% to 68.2%) of patients with a kappa score ranging from

A total of 66 patients were enrolled in this study. The mean age of 0.495 to 0.572. It was of moderate agreement. In psoriatic
the study group was 53.7±16.56 in years (range : 14 to 86 Years). erythroderma patients, we were able to elicit
Males outnumbered females in a ratio of 3.4:1. The total duration munromicroabscess, dilated blood vessel and suprapapillary
of disease ranged from 10 days to 20 years with an average thinning in 60%, 80% and 65% cases respectively. Presence of
duration of 3.9 years. The exacerbation of disease was from 7 mitotic cells was also specific for psoriasis but it was present in
days to 1 year with a mean of 1.9 months. Majority of male only 20% of cases. The biopsies of drug induced erythroderma
patients were involved in outdoor activities and were farmers patients had necrotic keratinocyte, basal cell vacuolization and
(39.4%) and laborers (16.67%). Majority of female patients were eosinophils in infiltrate in 62.5%, 75% and 87.5% of patients
housewives (80%). respectively. Spongiosis was present in 62.8% of patients of
eczema. But it was also present in 50 % of drug induced
Most common aggravating factor was seasonal variation. erythroderma patients and 10% of psoriasis patients. [Table 3] In
Seasonal exacerbation was present in about 51.51% of patients. five patients, clinical findings mismatched histopathological
Winter exacerbation was present in 40% of psoriasis patients and findings. In these patients, clinical findings suggested the
2.8% of eczema patients. Summer exacerbation was present in diagnosis of eczema but it came out psoriasis
54.2% of eczema patients and 25% of psoriasis patients. History histopathologically. [Table 4]
of atopy was present in 19 patients. Drugs were responsible in 8
patients. Most common cause of erythroderma in this study was eczema
of various types (53.03%), followed by psoriasis (30.30%), drug
History of preexisting skin disease was present in 30 patients induced (12.12%), lymphoma (1.515%), mycosis fungoides
(62.1 %). Other co-morbidities like hypertension were present in (1.515%) and idiopathic (1.515%). [Figure 1]
26 patients (39.3%), diabetes in 4 patients (6.06%), and
tuberculosis in 4 patients (6.06%). The site of onset of Discussion
erythroderma was scalp and face in 28 patients (42.4%), The approach to patients with erythroderma depends on their
extremities in 27 patients (40.9%), and trunk & abdomen in 11 previous dermatologic background. Patient with a preexisting
patients (16.67%). dermatoses are easy to diagnose. Otherwise, erythroderma
Most common clinical features were itching (98.48%), fever remains a diagnostic challenge, especially in those patients
(31.8%), shivering (40.9%), arthralgia (13.63%), without history of dermatologic diseases and who deny having
lymphadenopathy (62.1%), edema (51.5%), palmoplantar recently taken any medications.6
keratoderma (22.7%) and nail changes (57.8%) [Table1]. The In this study, the mean age of diagnosis was 53.7±16.56 years
clinical finding in psoriasis, dermatitis and drug induced (range: 14 to 86 Years) with men outnumbering women in a ratio
ertythroderma have been described in detail in Table 2. Most of 3.4:1. This is in accordance with various previous studies. 3, 6, 7
common nail change was beau’s line followed by shiny nails, However, in a recent study by Hulmani et al, male to female ratio
yellowish discoloration of nails, subungual hyperkeratosis, of 14:1 was noted.8
pitting, and onycholysis. In 3 patients, twenty nail dystrophy was In our study, most common cause of erythroderma was air borne
present. Investigations revealed anemia in 33.3%, increased contact dermatitis compared to Hulmani et al where most
ESR in 37.9%, abnormal TLC in 18.1%, abnormal LFT in common etiology was psoriasis.8 The different etiologies of
15.2%, hypoalbuminaemia in 34.8% and abnormal RFT in erythroderma found in various studies has been summarized in
9.09% of cases. Table 5.
Clinico-pathological correlation occurred in about 67% (range:

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S.No. Points PSORIASIS DERMATITIS DRUG
1 Age group Any Predominantly Elderly age group(5- 7 decade) Any
2 Seasonal Exacerbation winter Summer and spring No
3 Preexisting disease May May No
4 History of drug No No Yes
5 Disease onset Insidious Mostly chronic Acute
6 Site of onset Predominantly extensors and scalp Exposed surfaces Sometimes
Involvement of eyelids, other folds(ABCD) cephalo-caudal
7 Scaling Thick, large, silvery Fine Fine
8 Erythema Red, fiery red Fading red Red/ fading red
9 Nose sign Absent Seen Absent
10 Oozing, cracking, Absent Present Absent
fissuring, excoriation
11 Vesiculation Absent May be May be
12 Pustulation May be Generally Absent except (Secondary infection) May be
13 Skin Dry erythematous Glossy skin with lichenification Dry erythema
14 Itching Mild Severe Mild
15 Palmoplantar May be Common Absent
keratoderma (in some studies it is common)
16 Fever May be Gen. Absent May be
17 Shivering ++ ++ +
18 Edema + + ++
19 Arthralgia ++ Gen. absent ++
20 Lymphadenopathy ++ + ++
21 Nails ++ - -
Pitting ++ - -
Beau's lines - ++ -
Onycholysis ++ May be Absent
Shinning in nails - ++ -
Subungual hyperkeratosis ++ + -

TABLE 2 : Differences in clinical profile of erythroderma patients

Clinico-pathological correlation occured in about 67% (range:

63.6% to 68.2%) of patients. In a similar study by Zip et al, 4 each
set of pathological diagnoses was compared with the final
discharge diagnoses, a positive correlation of 86% was observed
in the nonblinded (original) diagnostic group as opposed to 66%
in the blinded group. The results of blinded group were in
accordance to our study which is also a blinded study. In another
study by Vasconcellos et al,1 one or more skin biopsies along
with clinical findings were diagnostic or suggestive of the
underlying disease in 63.6% of the cases. Khaled et al 14 reported
positive clinico–histological correlation in 77%, Jun Li et al 6 in
55.56% and Rym et al11 in 74% of patients.
The histopathology of eythroderma differs depending on the
underlying diagnosis. In our study, in psoriasis patients the
Figure 1: Etiology of erythroderma findings observed were munromicroabscess (60%), dilated
blood vessel (80%), suprapapillary thinning (65%) and mitotic
Lymphadenopathy was seen in 62.1% of our cases. Previous cells (20%). In similar study by Zip et al,4 biopsies of psoriatic
studies have reported its prevalence varying from 19% to 55%. erythroderma patients revealed suprapapillary thinning, dilated
6, 8–10
Nail changes were seen in 57.8% of patients. Nail changes blood vessel and munromicroabscess in 69%, 81% and 69% of
were beau’s lines, shinning in the nails, subungual hyperkeratosis, patients respectively.
pitting, yellowish discoloration and onychodystrophy. Similar The biopsies of drug induced erythroderma patients had necrotic
findings were present in other studies.8, 10 keratinocyte, basal cell vacuolization and eosinophils in

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 Histopathological Drug Psoriasis Eczema fissuring, presence of beau’s lines, nail discoloration are useful
Findings Induced for diagnosing eczema in erythroderma patients, but in our study
% % % we found that these changes were also present in some patients
Hyperkeratosis 87.5 100 94.2 of psoriasis. Thus these changes might help in diagnosis of
Parakeratosis 87.5 100 74.2 eczema but they are not diagnostic and a biopsy should be done
Munro's microabscess 0.0 60 0.0 in all patients to confirm diagnosis even when sure clinically.
Granular layer Comparison of our etiologic diagnosis with the previous studies
Normal 87.5 15.0 82.8 is compiled in table 4. In our case series, most common final
diagnosis was eczema. It is quite different from other studies
Hypergranulosis 12.5 5.0 11.4
where it constituted a minority group.
Hypogranulosis/Absent 0.0 80.0 5.8
Conclusion
Acanthosis 62.5 100.0 94.2
Regular 0 65.0 8.5 Although clinical diagnosis is possible in most cases,
histopathology is required to corroborate with clinical diagnosis
Irregular 62.5 35.0 85.7
and to avoid any misdiagnosis as clinical features might overlap,
Mitotic cell 0.0 20.0 0.0
for example psoriasis Versus eczema. Microscopical clues that
Spongiosis 50.0 10.0 62.8 might help in diagnosis are munromicroabscess, dilated blood
Suprapapillary thinning 0.0 65.0 2.9 vessel and suprapapillary thinning for psoriasis and necrotic
Necrotic keratinocyte 62.5 0.0 0.0 keratinocyte, basal cell vacuolization and eosinophils for drug
Basal cell vacoulisation 75 0.0 11.4 induced erythroderma patients. Erythroderma still remains a
Exocytosis 0.0 10.0 22.8 challenge and requires skills of the dermatologist.
Epidermotropism 0.0 0.05 2.9
Dilated blood vessels 0.0 80.0 0.0 How to cite this article:
Maheshwari A, Agarwal US, Meena RS, Purohit S, Thalore SK.
Infiltrate Clinicopathological correlation in erythroderma. Indian Journal of
Lymphohistiocytic 37.5 95.0 62.9 Clinical Dermatology. 2018;1:75-79.
Lichenoid 37.5 0.0 0.0
Mixed 12.5 5.0 28.5 References
Mononuclear 12.5 0.0 8.6 1. Vasconcellos C, Domingues PP, Aoki V, Miyake RK, Sauaia N,
Eosinophilic infiltrate 87.5 5.0 11.4 Martins JE. Erythroderma: Analysis of 247 cases. Rev Saude Publica.
1995;29:177–82.
Melanin incontinence 75.0 10.0 8.6
2. Botella-Estrada R, Sanmartin O, Oliver V, Febrer I, Aliaga A.
Erythroderma: A clinicopathological study of 56 cases. Ama Arch
TABLE 3: Histopathological findings Derm Syphilol. 1994;130:1503–07.
3. Hasan T, Jansen CT. Erythroderma: a follow-up of fifty cases. J Am
infiltrate in 62.5%, 75% and 87.5% of patients respectively. In Acad Dermatol. 1983;8:836–40.
study by Zip et al 4, necrotic keratinocyte and eosinophils in 4. Walsh NM, Prokopetz R, Tron VA, Sawyer DM, Watters AK, Murray
infiltrate were present in 50% of cases each. Microscopically, S, Zip C. Histopathology in erythroderma: review of a series of cases
eosinophils in infiltrate, necrotic keratinocyte and basal cell by multiple observers. J Cutan Pathol. 1994;21:419–23.
vacuolization were the most specific findings to diagnose a case 5. Sehgal VN, Srivastava G. Exfoliative dermatitis: A prospective study
of 80 patients. Dermatologica. 1986;173:278–84.
of drug induced erythroderma. In previous studies, spongiosis
was one of characteristic finding to diagnose a case of 6. Li J, Zheng HY. Erythroderma: A Clinical and Prognostic Study.
Dermatology. 2012;225(2):154-62.
erythroderma due to eczema, present in 62.8% patients. But it
7. Sehgal VN, Srivastava G, Sardana K. Erythroderma/exfoliative
was also present in 50 % of drug induced erythroderma patients dermatitis: a synopsis. Int J Dermatol 2004;43: 39–47.
and 10% of psoriasis patients. Thus as spongiosis was not one of 8. Hulmani M, Nandakishore B, Bhat MR, Sukumar D, Martis J, Kamath
the specific findings to diagnose a case of erythroderma due to G, et al. Indian Dermatol Online J. 2014;5(1):25-9.
eczema we had to collaborate it with other findings for 9. Bandyaopadhyay D, Chowdhury S, Roy A. Seventy five cases of
diagnosis. It is generally thought that oozing, cracking, exfoliative dermatitis. Indian J Dermatol. 1999;44:55–7.

S. Itching Oozing Lichenification Seasonal H/O Previous Palmoplantar Nail Scaling Histopathological Clinical
No. exacerbation Atopy H/O involvement changes Diagnosis diagnosis
1. Mild + - - - - - Beau's line Fine Psoriasis Dermatitis
2. Severe + + Summer + Eczema - Yello discoloration Fine Psoriasis Dermatitis
3. Severe + - Summer - - - - Fine Psoriasis Dermatitis
4. Mild + + Summer + + + Beau's line Fine Psoriasis Dermatitis
5. Severe + + - - Eczema - Beau's line Fine Psoriasis Dermatitis

TABLE 4: clinical findings of patients with mismatched histopathological findings

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Indian Journal of Clinical Dermatology | Volume 01 | Issue 03 | December 2018 78
10. Pal S, Haroon TS. Erythroderma: A clinico-etiologic study of 90 dermatitis. Indian J Dermatol Venereol Leprol. 2003;69:30–1.
cases. Int J Dermatol. 1998;37:104–7. 13. Chaudhary A, Gupte PD. Erythroderma: A study of incidence
11. Rym BM, Mourad M, Bechir Z, Dalenda E, Faika C, Iadh AM, et and aetiopathogenesis. Indian J Dermatol Venereol Leprol.
al. Erythroderma in adults: A report of 80 cases. Int J Dermatol. 1997;63:38–9.
2005;44:731–5. 14. Khaled A, Sellami A, Fazaa B, Kharfi M, Zeglaoui F, Kamoun
12. Sudho R, Hussain SB, Bellraj E, Frederick M, Mahalaxmi V, MR. Acquired erythroderma in adults: a clinical and prognostic
Sobhana S, et al. Clinicopathological study of exfoliative study. J Eur Acad Dermatol Venereol. 2010;24(7):781-8.

Study causes Pal Rym Bandyopadhyay Sudha Chaudhary Hulmani Our study
et al[10] et al[11] et al[9] et al [12] et al[13] et al[8]
Psoriasis 37.8 51.25 33.33 32 40 33.33 53.03
Eczema of various types 12.2 7.5 4 12 20 20 30.3
Ichthyosis 7.8 0 1.33 0 0 0 0
Pityriasis rubra pilaris 2.2 5.25 1.33 0 0 3.33 0
Scabies 2.2 1.25 3.33 0 0 0 0
Pemphigus foliaceus 5.6 6.25 5.33 4 0 0 0
Lichen planus 0 1.25 0 0 0 0 0
Atopic Dermatitis 0 0 13.33 8 6.66 6.6 0
Other Dermatoses 6.6 3.75 0 8 0 0 0
Drug Reaction 5.5 11.25 12 24 10 16.6 12.1
Malignancy 5.5 8.75 2.67 4 6.66 3.3 1.5
Mycosis fungoides 0 0 0 0 0 0 1.5
Idiopathic 14.6 7.5 21.33 08 16.6 16.6 1.5

TABLE 5: Comparison of different etiology of erythroderma in various studies

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