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ORIGINAL ARTICLE
Year : 2018  |  Volume : 7  |  Issue : 4  |  Page : 254-258

Pemphigus foliaceus: Clinicoepidemiological study at tertiary care center


1 Department of DVL, Government Medical College, Nizamabad, India
2 Department of DVL, Gandhi Medical College and Hospital, Hyderabad, India
3 Department of DVL, Gandhi Medical College, Secunderabad, Telangana, India

Date of Web Publication10-Jan-2019

Correspondence Address:
Dr. Sudha Rani Chintagunta
Department of DVL, Government Medical College, Plot No.#5, Jupiter Colony, Kakaguda, Kharkhana, Secunderabad, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JDRNTRUHS.JDRNTRUHS_34_17

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  Abstract 


Background: Pemphigus foliaceus (PF) is characterized by shallow erosions with erythema, scaling, and crusting over seborrheic areas of the face, scalp, and chest with characteristic histopathology and direct immunofluorescence (DIF).
Aim: To study the clinicoepidemiological profile of patients with PF and response to treatment, especially pulse therapy.
Materials and Methods: This was a prospective clinical and therapeutic study of 20 patients WITH PF, attending DVL Department, from May 2007 to April 2016. The diagnosis was made based on clinical features, histopathology, and DIF. Clinical variants of PF were studied, and severity was assessed based on body surface area involvement. After detailed evaluation, 18 patients started on pulse therapy [13 dexamethasone cyclophosphamide pulse (DCP), 3 dexamethasone azathioprine pulse (DAP), 2 dexamethasone-only pulse (DOP)]. Two patients were not started on pulse therapy for medical reasons.
Results: The most common age group affected was 51–60 years. Male: female ratio was 1:1. Clinical variants observed were classical localized – 4, classical generalized – 10, erythrodermic – 4, pemphigus erythematosus – 1, and acral vesiculopustular lesions – 1. Nail changes and small erosion on the inner aspect of the lower lip were present in two patients each. The average time to remission was 7.3 months. Of 18 patients, 14 patients responded well to DCP/DAP/DOP therapy. Two patients lost to follow-up in phase 1. Two patients had frequent relapses and started on methotrexate; the disease is under control in one patient.
Conclusion: PF usually localized to seborrheic areas; in our study, generalized papulosquamous lesions and erythroderma-like presentation were predominant. The majority of the patients showed remission with pulse therapy, and two patients require addition of immunosuppressants in the follow-up period.

Keywords: Clinical variants, dexamethasone azathioprine pulse, dexamethasone cyclophosphamide pulse, dexamethasone-only pulse therapy, pemphigus foliaceus


How to cite this article:
Chintagunta SR, Manchala S, Arakkal G, Jayanthi BS, Kabir BW. Pemphigus foliaceus: Clinicoepidemiological study at tertiary care center. J NTR Univ Health Sci 2018;7:254-8

How to cite this URL:
Chintagunta SR, Manchala S, Arakkal G, Jayanthi BS, Kabir BW. Pemphigus foliaceus: Clinicoepidemiological study at tertiary care center. J NTR Univ Health Sci [serial online] 2018 [cited 2019 Nov 21];7:254-8. Available from: http://www.jdrntruhs.org/text.asp?2018/7/4/254/249827




  Introduction Top


Pemphigus foliaceus (PF) classically presents with small flaccid bullae and moist corn-flake-like erosions in seborrheic distribution with minimal or no involvement of the mucous membranes. The variants include pemphigus erythematosus (PE) and endemic PF, immunoglobulin (Ig) A PF, and drug-induced. Rare presentations include erythroderma, lesions resembling seborrheic keratoses, erythematous, and vesicular lesions resembling DH and pemphigus herpetiformis.

The course of PF is chronic and less severe. Most cases of PF are treated with systemic corticosteroids with or without immunosuppressive therapy depending on the severity though mild cases respond to topical glucocorticosteroids alone.[1] Addition of immunosuppressive agents such as cyclophosphamide, azathioprine, methotrexate, and other adjuvants minimizes the side effects of systemic corticosteroids. Pulse [dexamethasone cyclophosphamide pulse (DCP)/dexamethasone-only pulse (DOP)/dexamethasone azathioprine pulse (DAP)/dexamethasone methotrexate pulse (DMP)] therapy, introduced by Pasricha and Gupta, has become standard treatment for pemphigus vulgaris (PV) and PF in India.[2] We studied 20 patients for the clinicoepidemiological profile and response to treatment. Although therapy for PF is less aggressive, we started pulse therapy in 18 patients as skin involvement was moderate to severe in all the cases. Two patients were managed with topical steroids along with cyclophosphamide 50 mg daily and azathioprine 50 mg, respectively.


  Materials and Methods Top


The study was done in the DVL Department from 2007 to till date. Twenty patients with PF confirmed by histopathology and direct immunofluorescence (DIF) were included. After obtaining informed consent from the patient, detailed history and thorough clinical examination were done. Clinical severity was assessed based on body surface area involvement as minimal (≤10%), moderate (11%–30%), and severe disease (>30% involvement). All the patients were subjected to Tzanck smear, skin biopsy for histopathology, and DIF. Routine investigations such as complete blood picture, blood sugar, serum electrolytes, liver function tests, renal function tests, complete urine examination, stool examination, ultrasound abdomen, chest X-ray, electrocardiography, and two-dimensional echo were done. The standard pulse therapy introduced by Pasricha and Gupta was given in four phases. In DCP phase I, dexamethasone 100 mg in 5% dextrose was given as slow intravenous (IV) infusion over 2 h for 3 consecutive days along with cyclophosphamide 500 mg on the second day; such pulses were repeated every 28 days. In phase II, similar pulses were given for 9 months. In phase III, oral cyclophosphamide 50 mg/day was given for 9 months. In phase IV, all the drugs were withdrawn and the patients were followed up. In DAP therapy, azathioprine 50 mg was given in between the pulses.


  Results Top


Twenty patients with PF were included in the study. The most common age group affected was 51–60 years. Male: female ratio was 1:1. The duration of the disease at presentation ranged from 1 month to 2 years, with an average of 8.9 months. The clinical variants of PF observed were classical localized – 4, classical generalized – 10, erythrodermic – 4, PE – 1, and acral vesiculopustular lesions on extremities – 1 [[Graph 1], [Figure 1],[Figure 2],[Figure 3],[Figure 4], respectively]. The extent of skin involvement was minimal, moderate, and severe in 5%, 25%, and 70%, respectively, of the patients. Erosions on the inner aspect of lower lip and nail changes were observed in two (10%) patients each. Other disease associations observed were uncontrolled hypertension with hypertensive retinopathy in one and diabetes, hypertension, and hypothyroidism in one.

Figure 1: Pemphigus foliaceus with erosions and scaling on trunk and extremities

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Figure 2: Pemphigus foliaceus with erythroderma

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Figure 3: Pemphigus erythematosus

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Figure 4: Pemphigus foliaceus with vesiculopustular lesions and mucosal erosions

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After detailed evaluation, 18 patients were started on pulse therapy (DCP – 13, DAP – 3, and DOP – 2). DOP and DAP were given for unmarried patients and who have not completed their family. Response to treatment and relapses if any were noted. In two patients, though the skin involvement was moderate to severe, because of uncontrolled hypertension, they were managed with cyclophosphamide 50 mg and azathioprine 50 mg, respectively, along with topical steroid. All investigations were repeated at monthly intervals and whenever necessary and were monitored for side effects. Treatment details are shown in [Table 1].
Table 1: Treatment Details of the Patients

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Of 18 patients on pulse therapy, 11 patients completed therapy and are in follow-up. Five patients are still on treatment in various phases (3 in phase 1, 2 in phase 2, and 11 in phase 3) and two patients were lost to follow-up in phase 1. In our study, the average time for clinical remission was 7.3 months in phase 1. Remission period after therapy (phase 4) varied from 18 months to 8 years. Two patients who completed therapy (one on DCP and one DAP patient) had frequent relapses in phase 4 follow-up. The two patients who completed DCP and DAP showed relapse at 18 months and 5 months, respectively, in phase 4 follow-up. Both were started on methotrexate, and presently, the disease is under control in one patient. Another patient was refractory to DCP and methotrexate. Subsequently, three doses of rituximab 375 mg IV were given without response; later, the patient expired due to septicemia. Two patients on DOP developed hypertension and cushingoid features during therapy in phase 1.


  Discussion Top


All forms of PF are characterized by superficial blisters and erosions and subcorneal acantholysis on histopathology and intercellular Ig deposits in the epidermis on DIF. The incidence and prevalence of PF are very low worldwide. In a recent analysis of 1209 patients with pemphigus in Iran,[3] the PV:PF ratio was found to be 12:1, and in a study by Karisetty et al.,[4] the ratio was 3:1, and the corresponding ratio in our study is 14:1. The proportion of PF cases was 22.5%, 14.8%, 10%–20%, and 3.6% in various studies, respectively.[5],[6],[7],[8]

PF is most common in the age group of 40–60 years, and both sexes are affected equally. The most common age group affected in our study was 51–60 years, which is in accordance to the study by Karisetty et al.[4] Male: female ratio in our study is 1:1. This is in contrast to 3:1 ratio that was reported by Cheung.[9] The average duration of symptoms before diagnosis was 8.95 months which is similar to the study by Cheung where average disease duration is 10.7 months.

The common presentation is localized involvement of seborrheic areas; rarely, the erosions can become generalized or present as erythroderma.[10],[11] Generalized erosions (50%) were the common presentation in our study. The other types observed were classical localized (20%), erythrodermic (20%), and acral vesiculopustular type and PE 5% each. Erythroderma and generalized involvement were reported in 3.1% and 53.1% in the study by Cheung; the corresponding percentages in our study were 20% and 50%, respectively.

PE case [Figure 3] showed IgG (3+) and C3c (1+) in the upper epidermis and basement membrane on DIF; antinuclear antibody profile was negative. Because of uncontrolled hypertension, this patient was managed with hydroxychloroquine 400 and 50 mg cyclophosphamide.

One patient presented with grouped vesiculopustular lesions limited to both forearms and legs without involvement of face and trunk. There was no response to repeated courses of antibiotics and 30 mg of prednisolone. Histopathology and DIF findings were consistent with PF and the patient was started on DAP therapy. PV with vesicles and bullae in acral distribution has been reported;[12] no such presentation was reported in PF as we observed in our study.

All the four patients who presented with erythroderma and histopathological examination and DIF findings were suggestive of PF. PF was estimated to cause erythroderma in approximately 6% of cases in a study by Pal and Haroon,[13] which is 20% in our study.

Mucosal involvement is rare in PF.[8] In our study, two patients (10%) had erosions on the inner aspect of the lower lip. Nail changes were observed in two (10%) patients, which include Beau's lines, longitudinal striations, and proximal onycholysis.

Treatment of PF is usually less aggressive. Mild or localized cases respond to topical glucocorticosteroids.[1] Patients with extensive disease require systemic steroid and other immunosuppressive drugs such as cyclophosphamide, azathioprine, methotrexate, amd cyclosporine.[14],[15] Rituximab and IV Ig[16],[17],[18] are useful in refractory cases.

Although the treatment of PF is less aggressive, the majority of our patients had moderate (25%) to severe (70%) disease and were started on pulse therapy. DCP, DAP, and DOP were given 13, 3, and 2 patients, respectively. Among 13 patients on DCP, 11 patients are on treatment and 2 patients were lost to follow-up in phase 1. Of 11 patients, 9 patients completed the therapy (in phase 4) and 2 are in phase 1. The average time taken for remission in phase 1 was 6.8 months. Remission period in phase 4 was 2–8 years with an average of 5.2 years. Of nine patients, one patient had relapse at 18 months.

In DAP group, one patient completed the therapy and two are in phases 1 and 2. The average time for remission in phase 1 was 5.3 months and remission period in phase 4 was 5 months. In DOP group, the average time for remission in phase 1 was 12.5 months. One patient is in phase 4, the remission period is 6.5 years, and the other is in phase 2. The first one developed hypertension in phase 1 and the second patient cushingoid features in phase 2.

The use of methotrexate in the therapy of pemphigus is well known.[14],[15] In this study, methotrexate 7.5–10 mg weekly was given for two patients who developed relapse during follow-up. One patient showed complete remission in 3 months. The other patient initially showed response followed by relapse within few months.

In summary, of 18 patients, 11 patients completed therapy. The remission period varied from 18 months to 8 years in phase 4 with the above regimens. Five patients are still on treatment in various phases. The average time for remission in phase 1 with DCP, DAP, and DOP was 6.8, 5.3, and 12.5 months, respectively. Remission period in phase 4 or follow-up period was 5.2 years, 5 months, and 6.5 years.

Limitations

  • Limited number of patients.



  Conclusion Top


In our study, generalized papulosquamous lesions and erythroderma-like presentation were predominant. Long-term remission was observed with DCP and DAP without significant side effects. Pulse therapy can be considered as treatment option in moderate-to-severe cases of PF to achieve long-term remission.

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

1.
Dumas V, Roujeau JC, Wolkenstein P, Revuz J, Cosnes A. The treatment of mild pemphigus vulgaris and pemphigus foliaceus with a topical corticosteroid. Br J Dermatol 1999;140:1127-9.  Back to cited text no. 1
    
2.
Pasricha JS, Gupta R. Pulse therapy with dexamethasone cyclophosphamide in pemphigus. Indian J Dermatol Venereol Leprol 1984;50:199-203.  Back to cited text no. 2
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Karisetty B, Reddy KN, Lahkar M. Prevalence of pemphigus vulgaris and pemphigus foliaceus in tertiary care hospital in India: An update. Pharm Innov J 2013;2:68-72.  Back to cited text no. 4
    
5.
Noorbala MT, Kafaie P, Poursina N, Ghavami M. Pemphigus in central part of Iran. J Pak Assoc Dermatol 2012;22:197-99.  Back to cited text no. 5
    
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Mahajan VK, Sharma NL, Sharma RC, Garg G. Twelve-year clinico-therapeutic experience in pemphigus: A retrospective study of 54 cases. Int J Dermatol 2005;44:821-7.  Back to cited text no. 6
    
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Pasricha JS. Pulse Therapy in Pemphigus and Other Diseases. 2nd ed. New Delhi: Pulse Therapy & Pemphigus Foundation; 2000.  Back to cited text no. 7
    
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Champion RH, Burton JL, Burns DA, Breathnach SM, editors. Intraepidermal immunobullous diseases. In: Textbook of Dermatology. Oxford: Blackwell Science Ltd.; 1998. p. 1847-65.  Back to cited text no. 8
    
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Cheung HC. Pemphigus foliaceus: A clinical study of 32 cases in Hong Kong. H K Dermatol Venereol Bull 2004;12:126-32.  Back to cited text no. 9
    
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Grekin SJ, Fox MC, Gudjonsson JE, Fullen DR. Psoriasiform pemphigus foliaceus: A report of two cases. J Cutan Pathol 2012;39:549-53.  Back to cited text no. 10
    
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Martin LK, Werth V, Villanueva E, Segall J, Murrell DF. Interventions for pemphigus vulgaris and pemphigus foliaceus. Cochrane Database Syst Rev 2009;(1):CD006263.  Back to cited text no. 11
    
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Gharami RC, Kumar P, Mondal A, Ghosh K. Dyshidrosiform pemphigus vulgaris: Report of an unusual case. Dermatol Online J 2010;16:10.  Back to cited text no. 12
    
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Pal S, Haroon TS. Erythroderma: A clinico-etiologic study of 90 cases. Int J Dermatol 1998;37:104-7.  Back to cited text no. 13
    
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Gupta R. Prolonged remission of pemphigus induced by dexamethasone-cyclophosphamide pulse therapy. Indian J Dermatol Venereol Leprol 2007;73:121-2.  Back to cited text no. 14
[PUBMED]  [Full text]  
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Katz KH, Marks JG Jr., Helm KF. Pemphigus foliaceus successfully treated with mycophenolate mofetil as a steroid-sparing agent. J Am Acad Dermatol 2000;42:514-5.  Back to cited text no. 15
    
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Herr AL, Hatami A, Kokta V, Dalle JH, Champagne MA, Duval M. Successful anti-CD20 antibody treatment of pemphigus foliaceus after unrelated cord blood transplantation. Bone Marrow Transplant 2005;35:427-8.  Back to cited text no. 16
    
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Tóth GG, Jonkman MF. Successful treatment of recalcitrant penicillamine-induced pemphigus foliaceus by low-dose intravenous immunoglobulins. Br J Dermatol 1999;141:583-5.  Back to cited text no. 18
    


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