10.5826/dpc.1204a160
Introduction: Erythroderma is a life-threatening dermatologic emergency which is characterized by diffuse erythema and exfoliation affecting more than 90% of the body surface area. Most common cutaneous diseases associated with erythroderma are systemic contact dermatitis, psoriasis, drug eruption and atopic dermatitis. Clinicopathological correlation is used to determine the underlying disease. In addition, direct immunoflurorescence (DIF) may provide significant clues for etiology of erythroderma especially in the case of autoimmune bullous skin diseases (ABSDs).
Objectives: In our study, we aimed to analyze the demographic data, clinical prediagnoses, final diagnosis, histopathological and DIF examination findings, accompanying systemic signs and laboratory abnormalities of erythrodermic patients.
Methods: We conducted a retrospective study of 31 erythroderma patients in a referral hospital between 2014 and 2021. Cutaneous biopsies were taken from all patients for Hematoxyin&amp;Eosin and DIF examination.
Results: Average age was 54. 6 ± 23 years. 48.4% of the patients were female (n=15) whereas 51.6 % of the patients were male (n=16). Average time between the onset of rash and biopsy was 18.8 days. DIF analysis showed immune deposits in 19.4% (n=6) of the patients; whereas no immune deposits were detected in 80.6% (n=25) of the patients. The most frequent final diagnosis was adverse cutaneous drug eruption followed by ABSDs.
Conclusions: Our findings suggest that DIF may be used in conjunction with clinicopathologic and clinical findings to reveal the associated skin diseases in erythrodermic patients. Erythrodermic patients presenting with clinical findings of ABSD should be considered for DIF examination.
text/xml
2160-9381
2082
en
Aysen Karaduman
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
erythroderma
Diagnostic Role of Direct Immunofluorescence Assay in Determining The Etiology of Erythroderma: Experience in a Tertiary Referral Hospital
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2022-10-31
2021-10-14
2022-10-31
2022-11-29
e2022160
Dermatol Pract Concept
Introduction: Erythroderma is a life-threatening dermatologic emergency which is characterized by diffuse erythema and exfoliation affecting more than 90% of the body surface area. Most common cutaneous diseases associated with erythroderma are systemic contact dermatitis, psoriasis, drug eruption and atopic dermatitis. Clinicopathological correlation is used to determine the underlying disease. In addition, direct immunoflurorescence (DIF) may provide significant clues for etiology of erythroderma especially in the case of autoimmune bullous skin diseases (ABSDs).
Objectives: In our study, we aimed to analyze the demographic data, clinical prediagnoses, final diagnosis, histopathological and DIF examination findings, accompanying systemic signs and laboratory abnormalities of erythrodermic patients.
Methods: We conducted a retrospective study of 31 erythroderma patients in a referral hospital between 2014 and 2021. Cutaneous biopsies were taken from all patients for Hematoxyin&amp;Eosin and DIF examination.
Results: Average age was 54. 6 ± 23 years. 48.4% of the patients were female (n=15) whereas 51.6 % of the patients were male (n=16). Average time between the onset of rash and biopsy was 18.8 days. DIF analysis showed immune deposits in 19.4% (n=6) of the patients; whereas no immune deposits were detected in 80.6% (n=25) of the patients. The most frequent final diagnosis was adverse cutaneous drug eruption followed by ABSDs.
Conclusions: Our findings suggest that DIF may be used in conjunction with clinicopathologic and clinical findings to reveal the associated skin diseases in erythrodermic patients. Erythrodermic patients presenting with clinical findings of ABSD should be considered for DIF examination.
Aysen Karaduman
2022/10/31
10.5826/dpc.1204a160
e2022160
Department of Dermatology and Venereology, Hacettepe University, Faculty of Medicine, Ankara, Turkey
2160-9381
erythroderma
en
e2022160
Diagnostic Role of Direct Immunofluorescence Assay in Determining The Etiology of Erythroderma: Experience in a Tertiary Referral Hospital
https://dpcj.org/index.php/dpc/article/download/2082/1770
  Diagnostic Role of Direct Immunofluorescence
Assay in Determining The Etiology of Erythroderma:
     Experience in a Tertiary Referral Hospital
    Ecem Bostan MD1, Ozay Gokoz2, Sibel Dogan1, Duygu Gulseren1, Neslihan Akdogan1,
        Basak Yalici-Armagan1, Sibel Ersoy-Evans1, Gonca Elcin1, Aysen Karaduman1


1 Department of Dermatology and Venereology, Hacettepe University, Faculty of Medicine, Ankara, Turkey
2 Department of Pathology, Hacettepe University, Faculty of Medicine, Ankara, Turkey



Key words: erythroderma, fluorescent antibody technique, immunobullous diseases, pathology
Citation: Bostan E, Gokoz O, Dogan S, et al. Diagnostic Role of Direct Immunofluorescence Assay in Determining The Etiology of
Erythroderma: Experience in a Tertiary Referral Hospital. Dermatol Pract Concept. 2022;12(4):e2022160. DOI: https://doi.org/10.5826/
dpc.1204a160
Accepted: January 14, 2022; Published: October 2022
Copyright: ©2022 Bostan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-
NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use,
distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing interests: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding author: Ecem Bostan, MD, Hacettepe University, Faculty of Medicine Department of Dermatology and Venereology,
Ankara, Turkey, Phone:03123051704, Fax: 0 3123054127, E-mail: bostanecem@gmail.com




  ABSTRACT             Introduction: Erythroderma is a life-threatening dermatologic emergency which is characterized by
                       diffuse erythema and exfoliation affecting more than 90% of the body surface area. Most common
                       cutaneous diseases associated with erythroderma are systemic contact dermatitis, psoriasis, drug
                       eruption and atopic dermatitis. Clinical-pathological correlation is used to determine the underlying
                       disease. In addition, direct immunofluorescence (DIF) may provide significant clues for etiology of
                       erythroderma especially in the case of autoimmune bullous skin diseases (ABSDs).
                       Objectives: In our study, we aimed to analyze the demographic data, clinical pre-diagnoses, final di-
                       agnosis, histopathological and DIF examination findings, accompanying systemic signs and laboratory
                       abnormalities of erythrodermic patients.
                       Methods: We conducted a retrospective study of 31 erythroderma patients in a referral hospital be-
                       tween 2014 and 2021. Cutaneous biopsies were taken from all patients for H&E and DIF examination.
                       Results: Average age was 54.6 ± 23 years, 48.4% of the patients were female (N = 15) whereas 51.6 %
                       of the patients were male (N = 16). Average time between the onset of rash and biopsy was 18.8 days.
                       DIF analysis showed immune deposits in 19.4% (N = 6) of the patients; whereas no immune deposits
                       were detected in 80.6% (N = 25) of the patients. The most frequent final diagnosis was adverse cuta-
                       neous drug eruption followed by ABSDs.
                       Conclusions: Our findings suggest that DIF may be used in conjunction with clinical-pathologic and
                       clinical findings to reveal the associated skin diseases in erythrodermic patients. Erythrodermic pa-
                       tients presenting with clinical findings of ABSD should be considered for DIF examination.



Original Article | Dermatol Pract Concept. 2022;12(4):e2022160                                                                         1
Introduction                                                        antisera against human IgM (Dako, dilution ratio: 1/20-1/40),
                                                                    IgG (Bio SB, dilution ratio: 1/25-1/100], IgA (Dako, dilution
Erythroderma (exfoliative dermatitis) is defined as wide-           ratio: 1/20-1/40) and C3 (Diagnostic BioSystems Inc., dilution
spread erythema and exfoliation involving more than 90%             ratio: 1/75-1/100) were applied to sections and incubated.
of body surface area [1]. Men seem to be more affected              Presence of any positive immunofluorescence staining with
compared to women male-to-female ratio ranging from 1.5             IgM, IgG, IgA and C3 antisera was evaluated under immu-
to 2.8 [1-3]. Average age at the onset differs among vari-          nofluorescence microscopy. Sex, age, dermatologic exam-
ous studies and reported to be 50.7 and 57 years in two             ination findings, accompanying systemic symptoms, clinical
recent reports respectively.3,4 Even though skin involve-           pre-­diagnoses, laboratory findings, elapsed time between the
ment is the predominant clinical picture of the condition,          onset of the rash and biopsy procedure, histopathologic find-
life-­threatening systemic complications such as tachycardia,       ings, presence of immune deposits in DIF analysis, final diag-
electrolyte imbalance, edema and unstable body temperature          nosis, treatment given and were evaluated and recorded. The
may ­accompany [3].                                                 underlying etiologies of erythroderma were divided into 4 cat-
    Erythroderma generally arises from the exacerbation and         egories as follows: ‘category 1 (ABSD)’, ‘category 2 (ACDE)’,
generalization of a pre-existing skin diseases, even though         ‘category 3 (vascular skin diseases)’ and ‘category 4 (miscel-
new-onset cutaneous eruptions such as adverse cutaneous             laneous other skin diseases) (Table 1). For cases with a final
drug eruptions (ACDE), psoriasis, systemic allergic con-            diagnosis of ACDE including drug rash with eosinophilia and
tact dermatitis (SACD), autoimmune bullous skin diseases            systemic symptoms (DRESS) syndrome, maculopapular drug
(ABSD) such as bullous pemphigoid, pemphigus foliaceus              eruption (MDE), Stevens-Johnson syndrome/toxic epidermal
may also be the cause [3,4]. Identification of the associated       necrolysis spectrum (SJS-TEN) and vasculitic drug eruption,
cutaneous disease is not always that easy and requires lon-         the most probable inciting drug/drugs were determined and
gitudinal evaluation of the patient to reveal the underlying        time between the onset of the erythroderma and first drug
cause and manage the complications.                                 intake was also evaluated.
    Histopathological examination of the lesional skin pro-
vides significant clues related to the etiology and thus may be     Statistics
the most fundamental evaluation to enlighten the pathogen-          Statistical analyses were performed with the IBM SPSS for
esis of erythroderma [5]. Direct immunofluorescence (DIF),          Windows Version 22.0 and MS Excel. Categorical variables
on the other hand, might prove to be quite useful in cases of       were given as frequencies and percentages. Numerical vari-
ABSD and leukocytoclastic vasculitis as the suspected causes        ables were summarized as mean ± standard deviation or me-
of exfoliative dermatitis by revealing the specific immune          dian (minimum-maximum).
deposition pattern in the biopsies taken from the perilesional
and lesional skin respectively [5,6].
                                                                    Results
    In our study, we aimed to determine the diagnostic role
of DIF in identifying the etiology of erythroderma and show         Demographical,      clinical,   pathological     characteristics;
the relationship between the presence of immune deposits            pre-diagnoses and final diagnoses of the all study subjects
and underlying diseases of exfoliative dermatitis.                  along with DIF findings and laboratory abnormalities are
                                                                    shown in Supplementary File 1.
                                                                       The average age of the subjects was 54. 6 ± 23 years
Methods
                                                                    (range: 3- 86 years, median: 61 years). 48.4% of the patients
The present study was a retrospective study conducted by re-        were female (N = 15) whereas, 51.6 % of the patients were
view of electronic medical data records and histopathologic         male (N = 16). All patients presented with erythema and
slide images belonging to 31 patients in a tertiary referral hos-   scaling covering > 90% of body surface area, 48.4 % of the
pital between January 2014 and September 2020. Ethics com-          patients (N = 15) had also one or more mucosal area (oral,
mittee approval was obtained (project number: GO 20/1099,           anogenital and ocular) involvement. All patients with SJS
decision number: 2020/19-45, decision date: November 17,            (N = 4), five patients with MDE, two patients with DRESS,
2020) and informed consent was taken from the participants          one patient with bullous mycosis fungoides, one patient
for the study. All the patients were diagnosed as erythroderma      with pemphigus foliaceus and two patients with SACD had
and cutaneous biopsies were taken for histopathological exam-       mucosal involvement. The most common clinical presenta-
ination and DIF analysis. Patients without histopathological        tions of oral mucosal involvement were hemorrhagic-crusted
and DIF examination were excluded from the study. For DIF           plaques covering the lips, erosions on the buccal and palatal
assay, skin tissue samples were frozen in a cryostat and then       mucosa which were predominantly observed in cases with
sectioned with a thickness of 5 µm. Then, fluorescein-labeled       SJS. Mucopurulent conjunctivitis, eyelid margin ulceration



2                                                                       Original Article | Dermatol Pract Concept. 2022;12(4):e2022160
and vulvovaginal/penile erosions were also present in pa-                the onset of rash and performing the biopsy was 18.8 ± 28.3
tients with SJS. Patients with MDE, DRESS and SACD most                  days (range: 1-150 days). DIF analysis showed immune de-
commonly had superficial erosions on the lips as the mu-                 posits in 19.4% (N = 6) of the patients; whereas no immune
cosal manifestation. The most frequent systemic symptoms                 deposits were detected in 80.6% (N = 25) of the patients.
and signs associated with erythroderma were fever (67.7%,                The final diagnoses of the underlying cutaneous diseases
N = 21), followed by pruritus (38.7 %, N = 12). Hypoten-                 were classified as ‘category 1 (ABSD)’, ‘category 2 (ACDE)’,
sion, pain, irritability, facial/peripheral edema, lymphade-             ‘category 3 (vascular skin diseases)’ and ‘category 4 (miscel-
nopathy, malaise, arthralgia and myalgia were also present.              laneous)’. Category 1 consists of bullous pemphigoid, pem-
                                                                 3
29% of the patients (N = 9) had eosinophilia (> 500/mm                   phigus foliaceus; category 2 consists of ACDEs including
cells); other accompanying laboratory anomalies are shown                SJS/TEN spectrum, DRESS, MDE, AGEP (acute generalized
in Supplementary Table 1. The average elapsed time between               exanthematous pustulosis), fixed drug eruption, vasculitic


         Table 1. Underlying etiologies of erythroderma and direct immunofluorescence findings.
                                                         Presence of any
                                    Number of       accompanying bulla, vesicle                 Direct
                                     Patients        pustule, erosion, crusting            Immunofluorescence
                                      N (%)                 or necrosis                        Findings                 Total (N, %)
 Category 1 (Autoimmune                                                                                                   3 (9.7%)
 bullous skin disorders)
 Bullous Pemphigoid                  2 (2.9%)         Bulla, crusting and erosion            Linear IgG and C3
                                                                                              deposition at the
                                                                                          dermoepidermal junction
 Pemphigus Foliaceus                 1 (1.4%)          Flaccid bulla, vesicle and        Intercellular IgG deposition
                                                                crusting
 Category 2 (Adverse                                                                                                    20 (64.5%)
 Cutaneous Drug Eruptions)
 Stevens-Johnson Syndrome/           4 (5.8%)            Erosion, crusting and                      None
 Toxic Epidermal Necrolysis                               Nikolsky (+) bulla
 Maculopapular drug                 10 (14.5%)                       -                      Only one patient had
 eruption                                                                                 linear IgM, granular IgG
                                                                                          and IgA deposition at the
                                                                                          dermoepidermal junction
 Drug rash with eosinopilia          3 (4.3%)                        -                              None
 and systemic symptoms
 Vasculitic drug eruption            1 (1.4%)                        -                              None
 Fixed drug eruption                 1 (1.4%)           Bulla, erosion, crusting                    None
 Acute generalized                   1 (1.4%)                    Pustule                            None
 exantematous pustulosis
 Category 3 (Vascular Skin                                                                                                3 (9.7%)
 Diseases)
 Purpura Fulminans                   1 (1.4%)        Hemorrhagic bulla, necrosis                    None
 Antiphospholipid syndrome           1 (1.4%)        Hemorrhagic bulla, necrosis                    None
 Leukocytoclastic vasculitis         1 (1.4%)                        -                              None
 Category 4 (Miscellaneous)                                                                                              5 (16.1%)
 Mycosis fungoides                   1 (1.4%)                    Bulla                   Interrupted C3 deposition
                                                                                          along dermal vessels and
                                                                                          dermoepidermal junction
 Psoriasis                           1 (1.4%)                        -                              None
 Psoriasiform dermatisis             1 (1.4%)                    Pustule                 Linear C3 deposition at the
 (finally diagnosed as                                                                        basal membrane
 idiopathic erythroderma)
 Systemic allergic contact           2 (2.9%)                        -                              None
 dermatitis



Original Article | Dermatol Pract Concept. 2022;12(4):e2022160                                                                       3
drug eruption; category 3 encompasses purpura fulminans,          from the intact skin just at the periphery of a bulla that had a
antiphospholipid syndrome and leukocytoclastic vasculi-           pre-diagnosis of bullous pemphigoid or pemphigus foliaceus,
tis, whereas category 4 consists of miscellaneous causes of       whereas skin samples were obtained from a vesicle, bulla or
erythroderma including, bullous mycosis fungoides, SACD,          pustule for the subjects who had pre-diagnosis of vasculitis
psoriasis and psoriasiform dermatitis (Table 1). Patients in      or drug eruption. All 3 cases of erythrodermic patients in the
category 3 (purpura fulminans, antiphospholipid syndrome          category 1 diagnosed with either bullous pemphigoid (N = 2)
and leukocytoclastic vasculitis) were accepted to present an      or pemphigus foliaceus (N = 1), 1 patient from category 2
erythrodermic-purpuric form of the disease described, since       diagnosed with MDE and 2 cases from category 4 diagnosed
>90% of the body surface area were covered with erythema          with bullous mycosis fungoides and psoriasiform dermatitis,
accompanied by hemorrhagic bullae and ecchymotic plaque.          respectively, showed positive immunofluorescence in DIF as-
The most frequent final clinical-pathological diagnosis was       say. Two cases of bullous pemphigoid showed linear IgG and
ACDE category (category 2) (64.5 %, N = 20) followed              C3 deposition at the dermoepidermal junction (Figure 4),
by bullous pemphigoid (6.5%, N = 2) and SACD (6.5 %,              whereas intercellular IgG deposition was detected in pem-
N = 2) (Table 1). The only patient diagnosed histopathologi-      phigus foliaceus.
cally with ‘psoriasiform dermatitis’ was accepted to have an
idiopathic form of erythroderma. Clinical and histopatho-
                                                                  Conclusions
logical pictures of erythrodermic patients with different un-
derlying etiologies are shown in Figures 1-5. Presence of any     To our knowledge, this is the first study which evaluates di-
accompanying pustule, bulla, vesicle, necrosis, erosion and       agnostic significance of DIF examination in clarifying the
crusting were also determined as the part of dermatological       etiopathogenesis of exfoliative dermatitis. Immunofluores-
examination as shown in table 1. For the category 2, the          cence microscopy is a well-developed, advanced technique
mean elapsed time between the onset of the rash and most          which is utilized for the detection of tissue-fixed antibodies.
probable inciting drug intake was 14.6 ± 13.9 days (range:        For cutaneous disorders, DIF is used for designation of the
0-42 days). The most common probable causes of erythro-           antibodies bound to a specific antigen in the skin [7]. DIF
derma were antimicrobials (40%, N = 8), followed by               assay simply involves the application of fluorescein-labeled
allopurinol (20%, N = 4), phenytoin (15%, N = 3), hydroxy-        secondary antibodies to a frozen section of sample tissue fol-
chloroquine (10%, N = 2), intravenous contrast media (10%,        lowed by examination of the issue for the deposition of im-
N = 2), chemotherapy agents (10%, N = 2) and others (15%,         mune reactants under immunofluorescence microscopy [7].
N = 3). The sample tissue for DIF examination was taken           DIF is generally considered to be an auxiliary tool which aids




               Figure 1. (A) Presentation of erythroderma in a patient diagnosed with mycosis fungoides widespread
               erythema and scaling. (B) Yellow/brown color change and subungal hyperkeratosis of the fingernails.
               (C) Diffuse dermo-epidermal atypical lymphoid infiltrate which shows epidermotropism (H&E, x200).



4                                                                      Original Article | Dermatol Pract Concept. 2022;12(4):e2022160
         Figure 2. (A) Dusky red, violaceous targetoid plaque and bulla formation in a patient with SJS. (B) In the same patient
         skin biopsy, vacuolar degeneration, necrotic keratinocytes and pigment incontinence compatible with Stevens-Johnson
         syndrome are observed (H&E, x200). (C) Widespread annular, polycyclic-erythematous plaques with scale involving the
         trunk and the extremities, (inset) closer view of the plaques in a patient finally diagnosed with idiopathic erythroderma.
         (D) Histopathological examination of the patient revealed psoriasiform dermatitis with sub-corneal pustule formation
         (H&E, x200). (E) Widespread erythematous, confluent patches and plaques on the trunk in a patient with drug eruption.
         (F) The same patient’s skin biopsy showed vacuolar degeneration at the basal layer, capillary congestion and perivascular
         eosinophilic and neutrophilic inflammation compatible with drug eruption.




                 Figure 3. (A) Erythroderma in a patient with psoriasis. Histopathological findings in an erythrodermic
                 patient diagnosed with psoriasis. (B) Subcorneal neutrophilic pustule (Kogoj pustule) formation is seen
                 (arrowhead, H&E, x100). (C) Hypo-granulosis and psoriasiform acanthosis are present (H&E, x100).




to reach the accurate diagnosis of various dermatologic dis-            In our study, we aimed to determine the diagnostic utility of
orders especially when supportive histopathological changes             DIF in patients with exfoliative dermatitis.
are minimal. In dermatology practice, incorporating DIF                     Erythroderma appears to affect men more than women
findings with routine pathological findings are particularly            even though in some studies no sex predilection is showed
useful in the patients pre-diagnosed with ABSD, connective              [3,10]. In line with the present data in the literature, our
tissue diseases and cutaneous vasculitis [7]. A study by Buch           study also showed a slight male predominance with a
et al showed that the sensitivity of DIF was 94.44% and                 male-to-female ratio of 1.07. The mean age of affect study
84% in the pemphigus vs bullous pemphigoid group respec-                subjects in our study was 54.6 ± 23 years (range: 3- 86 years,
tively [8]. DIF was shown to have diagnostic significance in            median: 61 years). In a retrospective study of 49 erythroder-
the classification of cutaneous small vessel vasculitides espe-         mic patients, the average age was reported to be 50.7 ± 17.9
cially in IgA vasculitis and lupus vasculitis [9]. In erythrod-         years which was in concordance with our findings [4]. As an
ermic patients, expeditious diagnosis of the underlying cause           acquired-adulthood disease, erythroderma may have various
is the essential step which enables the accurate intervention.          underlying etiologies or may be idiopathic in at least 25% of



Original Article | Dermatol Pract Concept. 2022;12(4):e2022160                                                                        5
           Figure 4. (A) Histopathological findings in an erythrodermic patient with bullous pemphigoid: sub-epidermal
           cleavage (arrowhead), eosinophilic spongiosis, superficial dermal edema and interstitial eosinophilic infiltration
           (H&E, x200). DIF revealed linear (B) C3 and (C) IgG deposition at dermoepidermal junction (DIF, x200).




                Figure 5. (A) Subcorneal/intragranular blister formation with neutrophils and few acantholytic cells
                (­
                 arrow). Dermal edema with mixed cellular infiltrate bearing eosinophil leukocytes (H&E, x200).
                (B) Basal cell vacuolization, spongiosis, necrotic keratinocytes, and lymphocyte exocytosis in the e­ pidermis.
                Lymphohistiocytic inflammation and a few extravasated erythrocytes in the dermis (H&E, x200).


the cases [11]. In the present study, the most frequent under-           dermatoses leading causes being psoriasis, eczema and atopic
lying etiology of erythroderma was ACDE followed by ABSD,                dermatitis, in contrast to our study [4,12,13]. In our retro-
SACD, psoriasis and mycosis fungoides. In two patients with              spective study, we only included erythrodermic patients with
diagnoses of mycosis fungoides and psoriasis, generalization/            available DIF examination results: this factor might explain
accentuation of the pre-existing dermatoses had evoked the               the discrepancy between the results of our study and other
erythrodermic status. In different studies, the most common              ones. Our results show that skin samples for DIF examina-
diseases associated with erythroderma were pre-existing                  tion were mostly taken from the patients with a suspected



6                                                                              Original Article | Dermatol Pract Concept. 2022;12(4):e2022160
diagnosis of bullous/vesicular or vasculitic skin diseases such   formation with neutrophils and few acantholytic cells which
as bullous pemphigoid, SJS, AGEP, FDE and leukocytoclas-          was compatible with pemphigus foliaceus (Figure 5). With
tic vasculitis etc. So we most likely missed other causes of      the aid of DIF examination which revealed intercellular IgG
erythroderma for which DIF analysis was not performed             deposition, the diagnosis of pemphigus foliaceus was con-
in our center, which could be considered as a selection bias      firmed. On the other hand Joly et al reported three black
which is the limitation of our study.                             African men diagnosed with lichenoid erythrodermic bullous
    In ACDE category, the most common causes of cutane-           pemphigoid [17]. In these patients, histopathological exam-
ous eruption were antimicrobials followed by allopurinol,         ination showed subepidermal bulla with lichenoid infiltrate
phenytoin, hydroxychloroquine, intravenous contrast media,        along with linear deposits of C3 along the basal membrane.17
chemotherapy agents and others. In concordance with our           Two erythrodermic patients in our study presented with
results, anticonvulsants, beta-lactams, allopurinol, rifam-       widespread intact/flaccid bullae, erosion and crust forma-
picin, trimethoprim-sulfamethoxazole and non-steroidal            tion. Histopathological examination revealed sub-epidermal
anti-inflammatory drugs are reported to be the leading            bulla, basal vacuolar degeneration and eosinophil-rich infil-
causes of acquired erythroderma in multiple studies [4,13].       trate. With the help of DIF analysis which detected linear
Only one patient in the ACDE group with a diagnosis of            deposits of IgG and C3 along the dermo-epidermal junction;
MDE showed deposits of linear IgM, granular IgG and IgA           the final diagnosis was bullous pemphigoid; the etiology of
deposition at the dermo-epidermal junction. We believe that       exfoliative dermatitis was unraveled.
this immunoreactant deposition which was observed only               In the category 4, the study subject with a final diagnosis
in one patient was most likely non-specific. Duhra et al re-      of bullous MF showed interrupted C3 deposition along der-
ported a case of paracetamol-induced fixed drug eruption          mal vessels and dermoepidermal junction in the perilesional
with intercellular deposition of IgG and C3 in the lesional       skin, whereas the case with the histopathological diagnosis
skin and suggested that immunoreactant deposition only in         of psoriasiform dermatitis and final clinical diagnosis of idio-
the affected skin might play a role in the recurrence of the      pathic erythroderma showed linear C3 deposition at the basal
lesions at the same site after a particular drug intake [14].     membrane in the perilesional skin. We believe that these C3
We want to underline the fact that MDE is a common cause          deposition are non-specific, thus does not seem to carry any
of erythroderma and negative DIF examination favors the           diagnostic significance as reported in a study by Leibold et al
diagnosis of MDE, when ABSDs, fixed drug eruption and             [18]. In this study, 41 non-lesional, sun-exposed skin samples
drug-induced vasculitis. In addition, two cases of TEN were       obtained from Mohs surgery sites, 21 specimens demonstrated
shown to exhibit diffuse homogeneous deposits of IgM, IgA,        interrupted, weak linear or granular staining with IgM, IgG,
IgG, C3c and C1q in the mid-epidermis of perilesional skin        IgA, Clq and C3 antisera [18]. On the other hand, the two
which was linked to the capacity of necrotic keratinocytes to     other patients with final diagnoses of leukocytoclastic vascu-
absorb immunoreactants [15]. Diffuse intraepidermal depo-         litis and vasculitis drug eruption did not show any immune
sition of immune deposits was thought to favor the early          deposition which might be linked to the long elapsed time
diagnosis of TEN [15]. In contrast with this report, we did       between the onset of rash and biopsy (14 days) for both cases.
not observe any immune deposition in 4 patients with a final      DIF analysis is suggested to be performed within the first 24
diagnosis of SJS-TEN.                                             hours to yield the best result [19]. Immunoreactants can not
    Overall, 6 (19.4%) patients showed immune deposition          be shown efficiently 24-48 hours after the lesion formation.
in DIF evaluation. All 3 cases of erythrodermic patients di-         Even though our study has limitations, in that it was a
agnosed with ABSDs had positive immunofluorescence in             retrospective study and only small number of erythrodermic
DIF assay. One patient was diagnosed to have pemphigus            patients who had undergone both histopathological exam-
foliaceus; whereas the final diagnosis for the 2 patients was     ination and DIF analysis were included, we would like to
bullous pemphigoid. One patient diagnosed with MDE and            underline that DIF assay may be used as an auxiliary tool in
two cases diagnosed with bullous mycosis fungoides and            enlightening etiopathogenesis of exfoliative dermatitis.
psoriasiform dermatitis, respectively showed positive immu-
nofluorescence in DIF assay. Grekin et al reported 2 cases
                                                                  References
of erythrodermic psoriasiform pemphigus foliaceus which
showed intercellular IgG deposition in DIF examination             1. Pal S, Haroon TS. Erythroderma: a clinico-etiologic study
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