Ocular involvement in pemphigus vulgaris without skin lesions: about a case

Pemphigus vulgaris (PV) is an autoimmune disease affecting the skin and mucous membranes. The condition can be confused with a number of disorders, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and erythema multiforme (EM), all of which are life-threatening. Immunohistological and histochemical analyzes remain the optimal methods to differentiate these diseases. There is still insufficient evidence regarding the true incidence rate of eye disease in PV as well as its distinct clinical types. This report aims to examine the case of a 62-year-old man with atypical ocular pemphigus vulgaris and to review the literature.

Introduction

Pemphigus vulgaris (PV) is a rare autoimmune disease characterized by the development of flabby blisters and erosions (usually in the oral cavity) on otherwise normal skin or mucous membranes. The immune hypersensitivity state can be confused with a number of other disorders, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and erythema multiforme (EM), all of which were previously considered the same disease. [1].

PV is often caused by an unusual allergic reaction or immune response to various antibiotics or medications. PV can be life-threatening if left untreated; it leaves a patient vulnerable and susceptible to a number of life-threatening complications, including infections and fluid and electrolyte disturbances. These problems can lead to severe sepsis and cardiopulmonary failure. A patient with an autoimmune disease should be treated as soon as possible to prevent the further development of dangerous complications [2].

Although research demonstrates that the oral cavity is the most common site of mucosal involvement, the ocular surface can also be affected, with the first report of ocular involvement in PV in 1975 [3]. Since then, a number of case studies of PV patients with ocular complications have been described. As these reports show, ocular involvement in PV is uncommon, although it is probably underdiagnosed, where the symptom occurs less than 17% of the time. [2,4].

Information from patient history, such as exposure to specific drugs or infections, and clinical information, such as skin blister characteristics, were helpful in differentiating between PV, SJS, TEN, or EM. A biopsy performed at the edge of a blister or inflamed skin and immunohistological and histochemical analyzes remain the optimal methods for differentiating these diseases; a simple biopsy alone gives only a suggestive diagnosis [5,6].

The paucity of data regarding the true incidence rate of ocular manifestations in PV could be due to a lack of large-scale surveys focusing on the issue. Also, only people with severe eye problems are included in case reports and previous case series. Eye symptoms are likely to be modest and inconspicuous, so a full eye examination is usually needed to discover minor changes [7,8]. This case provides an overview of diagnostic and treatment methods for underdiagnosed atypical pemphigus vulgaris with ocular involvement and no skin lesions.

Presentation of the case

A 62-year-old man with a history of coronary artery disease after four-vessel coronary artery bypass grafting and type 2 insulin-dependent diabetes mellitus was seen by his primary care physician for progressive mucositis with odynophagia and dysuria. Her symptoms included blood and sores on her lips; swollen lips; extreme pain when swallowing, speaking and urinating; irritation around and above the eyes; and sensitivity to light. Soon after, the patient began to develop conjunctivitis. The conditions were secondary to an unknown etiology.

A few weeks earlier, the patient had been diagnosed with Helicobacter pylori (H. pylori) gastritis on esophagogastroduodenoscopy (EGD), for which he was prescribed amoxicillin (which he had previously), clarithromycin and pantoprazole for 14 days. After taking these drugs, he first developed mucositis on his labia, then on his penile and rectal areas. He also began to experience erythema of the conjunctiva with lacrimation.

The patient was eventually presented to the hospital for inpatient evaluation after trying other outpatient treatments: viscous lidocaine, magic mouthwash, nystatin swish and swallow, and diflucan. During his initial hospital assessment, he was treated for a possible atypical viral or fungal infection. The infectious disease department was contacted and she was prescribed antibiotics, antifungals and antiviral medications and ordered further serologies. The patient’s condition did not improve; on the contrary, it got worse.

Blood serology was performed to measure antinuclear antibody (ANA) levels. As shown in the table 1, the test detected that the patient was ANA-positive, indicating an autoimmune disease. Titers were twice as high as the upper limit of the reference range. He also had increased levels of Chlamydia pneumoniae immunoglobulin G (IgG) titer, implying an immune response to previous exposure to the organism. Urine toxicology reported negative results for amphetamines, barbiturates, benzodiazepines, cocaine, methadone, opiates, PCP screening, THC, and oxycodone.

Laboratory parameters Reference ranges Patient values
ANA HEp-2 IgG (IU/mL) 1:19-1:80 1:160
Antinuclear BA (IU/mL) 1:19-1:80 1:160
IgG (IU/mL) 1:19-1:80 1:160
ANA titer (IU/mL) 1:19-1:80 1:160
ANCA IFA titer (IU/mL) 1:19-1:80 <1:20
Chlamydia pneumoniae IgG titer (IU/mL) 1:64 1:128
Mycoplasma pneumoniae IgM Negative
Herpes simplex virus (HSV) Negative
Enterovirus Not detected
Treponemal antibodies Not responsive

During his hospitalization, the patient tolerated an EGD with biopsy (which revealed mucositis) and two lip biopsies by an otolaryngologist (ENT). Due to the lack of skin involvement, an outpatient dermatologist and plastic surgeon at another facility determined that SJS and TEN were unlikely to be the cause of the symptoms. The dermatologist assessed the patient via telemedicine and determined that he had “bullous disease” with paraneoplastic pemphigus or an autoimmune disease; the doctor then recommended high-dose steroids to combat the pervasive problems. Although there were no blisters on the skin, the skin on the patient’s elbows and abdomen began to break down.

After careful consideration, it was inferred that these symptoms, including the initially diagnosed mucositis, were related to a drug-induced allergic reaction. Lip histopathology results suggested pemphigus vulgaris. Biopsy showed spongiosis in the lower spinous cell layers, as well as suprabasal epithelial clefts. Lymphocytes and neutrophils were detected as the main cells causing an inflammatory response in clefts. The biopsy also demonstrated acantholysis in the lower spinous cell layers with detached keratinocytes. To confirm these results, direct immunofluorescence tests on freshly biopsied tissues were necessary; the technique gave a definitive diagnosis, as it demonstrated immunoglobulin G (IgG) antibodies in the spinal cell junctions of the lips. The positive level of IgG in the patient confirms these results. Following this discovery, previous medications were stopped and steroid medications were given to aid the healing process.

Discussion

Pemphigus vulgaris is recognized by “flaccid, mucosal or mucocutaneous blisters” [9]. In most affected individuals, the oral mucosa is primarily affected (with other mucous membranes sometimes also involved). Typically, skin lesions form anywhere on the integument [10]. However, there seem to be rare and atypical cases where the skin lesions do not show up on the patient, which can lead to a delayed or misdiagnosis.

Eye symptoms experienced by the patient were burning sensation and irritation around and above the eye, foreign body sensation in the eye, sensitivity to light and dry eyes. At first, the absence of skin lesions intrigued the doctors, but after the suggestive biopsy of the lips and the confirming direct immunofluorescence, the patient was diagnosed and promptly treated for pemphigus vulgaris.

There is controversy in the management of atypical ocular PV because it can be self-limiting. Treatment with antibiotics, antifungals, antivirals, and/or other drugs and medications can make the disorder worse. As the case report shows through patient endoscopy, autoimmune disease results from a drug-induced response; adding drugs or drugs can cause more antinuclear antibodies to be produced, which would lead to secondary aggravation of the mucous membranes [11]. Thereby, different treatment methods should be used to ensure the safety and full recovery of the patient.

First of all, immunohistology or immunofluorescence tests are necessary to establish a definitive diagnosis. Simple biopsies give only suggestive analyzes for the diagnosis; they may demonstrate acantholysis, but IgG antibodies are only demonstrated by direct immunofluorescence. Pathology of the conjunctiva was not obtained because the first specimen identified the problem. A tissue sample should be taken from the edge of an affected lesion to include mucosal tissue just outside the lesion to include adequate non-blistered and non-ulcerated tissue for proper evaluation. In addition, indirect serological tests could also be considered. Then the same treatment used for similar diseases (i.e. SJS, TEN and EM) is done to fight PV: stopping medication for five days and using steroids and agents immunosuppressants. [1]. Antibiotics may be given cautiously after the dead period to combat any ongoing infection, although the patient should be carefully monitored to ensure that the disease does not worsen.

conclusion

Pemphigus vulgaris can be life-threatening if left untreated and treated. A patient diagnosed with PV will likely be identified by problems caused by infectious diseases and should seek treatment immediately. The absence of skin lesions, combined with infrequent eye involvement, can lead to similar atypical cases of unrecognized and undiagnosed PV. However, this report presented the symptoms and diagnostic methods of this rare autoimmune disease.

To begin treatment, a simple biopsy should first be taken from the edge of a blister or inflamed skin and should be combined with immunohistology or immunofluorescence testing to make a definitive diagnosis. Then the patient must stop receiving medication for five days. After the dead period, a patient may be given steroids to aid in recovery.


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