Letters to the Editor

7. Yudin MH, Kaul R. Progressive hypertrophic genital herpes in an

This is an open access article distributed under the terms of the Creative
HIV‑infected woman despite immune recovery on antiretroviral
Commons Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows
therapy. Infect Dis Obstet Gynecol 2008;2008:592532. others to remix, tweak, and build upon the work non‑commercially, as long as the
8. Perkins N, Nisbet M, Thomas M. Topical imiquimod treatment of author is credited and the new creations are licensed under the identical terms.
aciclovir‑resistant herpes simplex disease: Case series and literature
review. Sex Transm Infect 2011;87:292‑5. Access this article online
9. Lascaux AS, Caumes E, Deback C, Melica G, Challine D, Agut H,
Quick Response Code: Website:
et al. Successful treatment of aciclovir and foscarnet resistant herpes
simplex virus lesions with topical imiquimod in patients infected with www.ijdvl.com
human immunodeficiency virus type 1. J Med Virol 2012;84:194‑7.
DOI:
10. Tangjitgamol S, Loharamtaweethong K, Thawaramara T,
10.4103/0378-6323.199423
Chanpanitkitchot S. Vulvar pseudoepitheliomatous hyperplasia
associated with herpes simplex virus type II mimicking cancer in an PMID:
immunocompromised patient. J Obstet Gynaecol Res 2014;40:255‑8. *****
11. Deza G, Martin‑Ezquerra G, Curto‑Barredo L, Villar García J,
Pujol RM. Successful treatment of hypertrophic herpes simplex
genitalis in HIV‑infected patient with topical imiquimod. J Dermatol How to cite this article: Camasmie HR, Barbosa C, Lupi O, Lima RB,
2015;42:1176‑8. Serra M, D'Acri AM, et al. Extensive and refractory genital herpes in
human immunodeficiency virus-infected patient successfully treated
with imiquimod: Case report and literature review. Indian J Dermatol
Venereol Leprol 2017;83:256-9.
Received: August, 2016. Accepted: August, 2016.
© 2017 Indian Journal of Dermatology, Venereology, and Leprology | Published by
Wolters Kluwer - Medknow

Oral magnesium chloride: A novel approach in the

management of Hailey–Hailey disease
Sir, chloride solution containing approximately 300 mg of elemental
Familial benign chronic pemphigus or Hailey–Hailey disease is a rare magnesium, which was prepared by dissolving 33 g of magnesium
autosomal dominant acantholytic disorder clinically characterized by chloride in 1 L of distilled water. The magnesium solution was
flaccid bullae and erosions in the intertriginous areas, mainly the axillary taken before breakfast every day. Clotrimazole dusting powder
and inguinal region. We report the unexpected, dramatic and persistent and fusidic acid cream were continued. A significant improvement
clinical improvement in long‑standing cases of Hailey–Hailey disease, in the skin lesions was noted after 15 days of treatment and an
with daily intake of a solution containing magnesium chloride. almost complete remission of signs and symptoms was obtained
after 4 weeks [Figures 4 and 5]. No side effects were reported
Case 1: A 34‑year‑old woman presented with macerated fissured by the patient, except for the unpleasant taste of the solution.
plaques in the axilla and the groin, bilaterally, for 3–4 years The patient’s quality of life significantly improved. The pre‑ and
with increased severity for the past 2–3 months. She also had post‑treatment serum levels of electrolytes, in particular, calcium,
a few crusted lesions in the angle of the mouth for 2 months. magnesium and zinc, were within normal limits. The patient is still
The cutaneous lesions started as tiny flaccid vesicles on an on treatment for 4 months, with sustained remission. We plan to
erythematous base, which ruptured easily and had a tendency to continue the magnesium chloride solution for 6 months and then
spread peripherally, producing a circinate plaque with crusting and taper the dose.
fissures. These lesions were associated with burning sensation and
malodor. There were multiple episodes of exacerbation of these Case 2: The 40‑year‑old brother of the first patient presented with
lesions, especially in summer. Her mother and brother suffered multiple erosions developing on and off in both axillae for 9 years,
from similar lesions. The patient had been treated in the past with itching and burning sensation [Figure 6]. No other flexural
with various oral and topical antibiotics and antifungals, with no areas were involved. He was taking oral dapsone 100 mg along with
response. The general physical examination of the patient revealed topical steroid and antifungal creams for 6 months, with no relief.
erythematous, macerated plaques with multiple fissures and crusts He was also investigated with a skin biopsy, potassium hydroxide
in the axillary and inguinal areas and slight crusting near the angle and Tzanck smear. The skin biopsy obtained was consistent
of mouth [Figures 1 and 2]. Other areas of the skin, mucosal with Hailey–Hailey disease. All the routine hematological and
surfaces and nails were normal. All the routine hematological and biochemical investigations were within normal limits.
biochemical investigations were normal. A potassium hydroxide
smear for fungal elements was negative, whereas Tzanck smear He was also treated with 70 ml oral magnesium chloride solution
showed some acantholytic cells. Biopsy taken from the axilla after stopping dapsone and the steroid cream. He responded well
demonstrated intraepidermal acantholysis resulting in a dilapidated within 15 days, with almost complete healing of erosions and did
brick wall appearance [Figure 3]. Direct immunofluorescence not complain of any adverse effect of magnesium chloride solution.
testing was not done. The final diagnosis of Hailey–Hailey disease His biochemical parameters after 1 month were within normal
was made on the basis of history, clinical and histopathological limits. The patient is still continuing treatment without any relapse
features. The patient was treated with 70 ml of oral magnesium [Figure 7].

Indian Journal of Dermatology, Venereology, and Leprology | March-April 2017 | Vol 83 | Issue 2 259
Letters to the Editor

Figure 2: Macerated plaque with painful fissures of the groin

Figure 1: Macerated plaque with painful fissures of the axilla

Figure 3: Characteristic intraepidermal separation with dilapidated brick wall

appearance (H and E, ×400)

Hailey–Hailey disease is inherited as an autosomal dominant trait

with incomplete penetrance. A positive family history is obtained
in about two‑thirds of patients. The disease, which typically occurs
between the second and fourth decades of life, usually around
puberty, has a chronic fluctuating course with remissions and
relapses triggered by friction, stress, sweating, heat, moisture,
superinfection, ultraviolet radiation or tissue damage. The fingernail
alterations, when present are highly typical, while mucosal
involvement, including the vulvovaginal area, is rare but possible.

The genetics and pathophysiology of Hailey–Hailey disease have

been linked to about 100 mutations in the ATP2C1 gene, encoding
for the Golgi secretory pathway Ca2+/Mn2+‑ATPase protein 1.1 Figure 4: Clearing of maceration at the end of a month in the axilla

260 Indian Journal of Dermatology, Venereology, and Leprology | March-April 2017 | Vol 83 | Issue 2
 Letters to the Editor

Figure 5: Clearing of maceration at the end of a month’s treatment in the groins Figure 6: Fissuring with erythema in the axilla of the second patient

and the differentiation of keratinocytes as well as the assembly of

desmosomes. The Ca2+‑ATPases are key actors in the regulation
of Ca2+ in eukaryotic cells. They comprise three families of
phosphorylation‑type that contribute to the correct functioning of cell
machinery namely: plasma‑membrane Ca2+‑ATPases that extrude
Ca2+ out of the cell, and sarcoendoplasmic reticulum Ca2+‑ATPases,
and secretory pathway Ca2+/Mn2+‑ATPase that pump Ca2+ into the
lumen of intracellular stores.5 The energy required for all Ca2+ pumps
are derived from adenosine triphosphate by catalyzing hydrolysis
in two Mg2+‑dependent steps. The Mg2+ ion regulates the activity
of plasma membrane Ca2+‑ATPase, wherein high intracellular
Mg2+ concentration (>2 mM) plays an inhibitory role in human
red blood cells.6 Hence, magnesium supplementation reduces the
extrusion rate of Ca2+ and increases intracellular Ca2+ sequestration.
The intracellular calcium to magnesium ratio varies from 4:1 to
1:1 (calcium/magnesium). The efficiency of magnesium absorption
varies inversely with the quantity of magnesium intake. The
magnesium is absorbed into the body primarily from the ileum of
the small intestine. The recommended dietary intake of magnesium
is between 360 and 410 mg a day. Excessive magnesium intake does
not usually cause toxicity because the body eliminates the excess
amounts. The side effects of excess magnesium intake are nausea,
diarrhea, loss of appetite and rarely, change in mental status. The
lethal dose of magnesium chloride (LD50) given intravenously is
176 mg/kg in rats.7

Treatment with magnesium chloride results in a change in the

Figure 7: Healing of fissure with postinflammatory hyperpigmentation in the intracellular calcium hemostasis which may be the molecular
axilla of the second patient basis for the therapeutic response in Hailey–Hailey disease. Wider
studies are warranted to assess the consistent efficacy and safety and
The Ca2+/Mn2+‑ATPase protein 1 transports Ca2+ and Mn2+ and it molecular studies are required to establish the complete mechanism
sequesters Ca2+ within the Golgi lumen. The human keratinocytes of action of magnesium chloride in this disease.
depend solely on this pump for loading the Golgi stores with Ca2+.
It plays a crucial role in setting up the cytosolic Ca2+ oscillations Financial support and sponsorship
known to control many vital cell functions, through cycles of Nil.
release and re‑uptake of internal Ca2+ stores. The defective Ca2+/
Mn2+‑ATPase protein 1 affects the processing of desmosomal Conflicts of interest
components, leading to the loss of cell–cell adhesion and consequent There are no conflicts of interest.
acantholysis. 2,3 Hence, the main mechanism of acantholysis is due
to ATP2C1 mutation which leads to depletion of Ca+ in Golgi lumen,
which results in impaired processing and reduced concentration of
junctional protein, finally leading to acantholysis. Borghi et al. first
Nitin G. Barde, Dharmendra B. Mishra,
noted improvement in Hailey–Hailey disease with the use of oral
magnesium chloride in a patient who was taking it for arthritis, Shraddha O. Ingole
as suggested by her close friend.4 The role of Ca2+ in the disease Department of Skin and VD, Indira Gandhi Government Medical College,
development is well documented. It regulates the proliferation Nagpur, Maharashtra, India

Indian Journal of Dermatology, Venereology, and Leprology | March-April 2017 | Vol 83 | Issue 2 261
Letters to the Editor

Correspondence: Dr. Nitin G. Barde, This is an open access article distributed under the terms of the Creative
Department of Skin and VD, Indira Gandhi Government Medical College, Commons Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows
C.A. Road, Nagpur ‑ 440 018, Maharashtra, India. others to remix, tweak, and build upon the work non‑commercially, as long as the
E‑mail: nitinbarde@gmail.com author is credited and the new creations are licensed under the identical terms.

References Access this article online

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Low‑dose cyclosporine for rapid remission and maintenance

in recurrent Kimura’s disease
Sir, gradually tapered and stopped within 3 months. The patient
A 66‑year‑old man, on regular treatment for diabetes and continues to be in remission 3 months after stopping cyclosporine
hypertension, presented with an asymptomatic insidious growth A [Figure 3].
on the left side of the face for 15 years. Thirteen years ago, the
swelling had been excised and reported as inflammatory granuloma.
However, this was followed by regrowth and a partial superficial
parotidectomy was done 6 years ago which was reported as benign
lymphoepithelial sialadenitis. Now, the patient had presented
with another recurrence. On examination, a 12 cm × 10 cm firm,
diffuse, mobile, non‑tender, nodular swelling was present on
the left parotid region extending from the preauricular area to
the angle of the mouth, becoming pendulous anteriorly. Orbital
involvement was seen superiorly [Figure 1a]. Satellite nodes
were not palpable. Contrast‑enhanced computerised tomography
showed a well‑defined, large, heterogeneous lesion in the
subcutaneous and muscular plane [Figure 1b]. Histopathology
revealed blood vessels surrounded by lobular infiltration of
lymphocytes and numerous eosinophils forming microabscesses.
An infiltrate of eosinophils was seen extending into the septa
of subcutaneous tissue [Figure 1c]. Immunohistochemistry for
IgE was strongly positive and peripheral blood eosinophilia of
27% was also noted. The baseline renal parameters were normal.
Based on clinical features and histopathology, a diagnosis of
Kimura’s disease was made. He was started on prednisolone
1 mg/kg/day following which the swelling regressed almost
completely in 2 months [Figure 2]. However, it relapsed every
time prednisolone was tapered to a low dose. After 8 months,
prednisolone was discontinued and cyclosporine A 2 mg/kg/day
was initiated, followed by rapid reduction in swelling within
10 days. Blood pressure, renal function, lipid levels and
electrolytes were monitored closely during therapy. Though our
patient was hypertensive, he did not develop any further rise Figure 1a: A 12 cm × 10 cm firm, nodular, protuberant, swelling on the left
in blood pressure after starting cyclosporine A. The drug was side of the face

262 Indian Journal of Dermatology, Venereology, and Leprology | March-April 2017 | Vol 83 | Issue 2