Acta, vol. 45 - 2003

UNUSUAL COURSE OF TREATMENT OF A PATIENT DIAGNOSED WITH PEMHIGUS VULGARIS (CASE REPORT)

Kaloudova Y.¹, Votava M.², Rihova H.¹, Suchanek I.¹, Brychta P.¹

¹Department of Burn and Reconstructive Surgery, Faculty Hospital,
²lnstitute for Pathology and Anatomy, Medical Faculty, Masaryk University, Brno, Czech Republic

SUMMARY. The case report is describing patient with an autoimmune disease. Pemphigus Vulgaris. This patient arrived to the general practitioner with Pemphigus Vulgaris after 20 days from the first manifestation of the disease. Despite intensive care, patient dies forty-seventh day after first clinical manifestation of the illness of candidernia. Candid, asis was diagnosed only in postmortem examination.

ZUSAMMENFASSUNG
Ungewohnlicher Therapieverlaut bei einer Kranken mit Pemphigus Vulgaris (Kasuistik).

In der Kasuistik wind der Fall einer Kranken mit Pemphigus Vulgaris beschrieben. Die Kranke lies sich von einem Arzt erst 20 Tage oath der Erscheinung der Krankheitssymptome behandeln. Trotz intensiver Therapie starb die Kranke oath 47 Tage der Krankheitsdauer an den Folgen der Candida-Sepsis.

Key words: pemphigus vulgaris, candidiasis, candidemia, sepsis

Pemphigus Vulgaris is an autoimmune disease with manifestation on skin and mucous membranes. Multiple vesicles with clear or bloodstained contents form, particularly in oral cavity and on the skin. The disease is caused by autoantibody to glycoprotein antigens contained in intercellular substance (ICS) and basal membrane (BM) of 'a skin and mucous membranes. Reaction of autoantibody with antigen causes typical ACANTHOLYSIS in Pemphigus Vulgaris with the formation of suprabasal vesicles. In the superior part of dermis form perivascular inflammatory infiltrates. The cause is unknown, literature talks about Pemphigus caused by medication (penicilamin, captopril)(1). If untreated, this disease is fatal in a course of five months to five years. The disease occurs in middle and advanced ages in both genders and all races. The most common cause of death is secondary infection.

Diagnosis Pemphigus Vulgaris is confirmed by histology, immunofluorescence and determination of antiepidermal antigens in plasma (ICS/BM).

Causal Therapy Principle is in application of high dose of steroids intravenous application of antibiotics and after the reduction of dose of steroids, immunosuppressive therapy is initiated. The disease has a tendency to be chronic in majority of cases.

CASE REPORT

Anamnesis

At the beginning of February 2002 (reputedly patient was healthy) patient experienced fever 38 to 38,5 °C, lasting one day. At the same time, generalized eruption of vesicles appeared on 40% of body surface and in oral cavity. Patient was not seriously ill prior to falling sick, did not take any medication in the past few months and denied any allergies. Patient did not see medical doctor and for 20 days, was treating herself at home with chamonilla exctract. Vesicles gradually fused to extensive erosions, which understandably got infected. The twenty-first day patient visited general practitioner and was immediately referred for hospitalization in First Dermatological Clinic at Faculty Hospital in Brno. Intravenous therapy with corticoids, antibiotics (Zinacef, Ciprofloxacin), antihistamines and analgesics was initiated. Locally areas were treated with application of tulle gras with Bactroban and Panthenol.

Microbiology: 21s' day (day of the admission to First Dermatological Clinic):

Oral swabs: Escherichia Coli sporadic, yeast culture negative.

Swabs from eroded areas: Escherichia coli, Staphylococcus aureus, and yeast culture: also negative.

25^th day

Swabs from eroded areas: Pseudomonas species, yeast culture not proved.

Diagnosis of Pemphigus Vulgaris was confirmed by histological and immunological analysis.

Histology: section of dermis excised from lower abdomen

• suprabasal vesicles with signs of acantholysis
• in the superior part of dermis perivascular inflated infiltrates

(Lymphocytes, Granulocytes, occasionally eosinophils).

To demonstrate the development of the disease, days of treatment are numbered, starting from the first manifestation of Pemphigus Vulgaris, first eruption of papulous exanthema.

25^th day

Worsening of patient's condition, fever 38,5 to 40,5 °C, shivering, circulatory failure tachycardia, hypotension, 110/60, somnolence, respiratory insufficiency of mild degree.

26^th day

Patient was transferred to the Intensive Care Unit for intensive care and nursing care to the extensive infected weeping areas in the operating room under general anesthesia with sterile precautions.

Status at the admission to our department: Patient is oriented, without breathlessness at rest and cyanosis, decreased shin turgor; patient in pain, extensive eroded areas on trunk and extremities, with massive secretion in 409, of body surface, on dorsum of both feet pink scars after healed fine erosions (Fig. 1, Fig. 2). Multiple erosions with hemorrhagic crusts in oral cavity, tongue with yellow coating, sticks out in midline, no signs of deep vein phlebitis or thrombosis, urine macroscopically clear, neurological examination normal, axillary temperature 37 °C, signs of mild dehydration. We continued with therapy with high dosage of steroids (Solu-Medrol 285 mg /day...245 mg/day), broadspectrum aratibiotics (combination of Oxacilin and Fortum) according to the bacterial sensitivity, were administered to the central venous system together with antimycotics (Diflucan 200 mg/day). In addition intravenous low-molecular heparin was administered continually as well as correction of the disintegration. of internal environment. Air mattress was used. Locally all areas were treated under sterile precautions in general anesthesia in the operation room. Dermazin was cautiously applied on, erupted areas as well as tulle gras and dressing with 2% solution of persteril. Infection of by Pseudamonas species and Enterococcus faecalis was confirmed and patient was treated with antibiotics according to given sensitivities. Repeatedly negative bacteriological outcomes were achieved from swabs from eroded areas, oral cavity, urine, stool, and hemoculture, correlating with significant reduction o/' figures C-reactive protein (CRP) and erythrocyte sedimentation.

In samples, sent to microbiology, yeast or fungus was not found in routine cultivation.

In our department specific cultivation of samples for mycosis was not requested, because clinical status did not evoke suspicion pointing towards mycotic superinfection. Antimycotics (Fluconazol) were administered without interruption during the whole hospitalization (at first intravenous, later per as). This is a standard antimycotic prevention that is used in treatment with broadspectrum antibiotics, during leucopenia and in patients that are immunosupressed by long term treatment with corticoids.

Patient presented with leukopenia and hyperfibrinemia during the whole hospitalization. All arena gradually epithelized, oral cavity gradually healed and patient was eating. Patient also mobilized out of bed. Because of primary disease we have been decreasing dose of corticoids only gradually. Immunological check up has shown regression of Pemphigus.

Skin defects Eradually cleared and healing was good. The 45^th day from the beginning of the first symptoms 90% of all areas were healed.

46^th day from the beginning of the disease there was a critical change. Patient suddenly lost consciousness, become somnolent to soporic with right-sided hemiparesis. Patient developed acute respiratory and circulatory insufficiency with hypotension as well. Two hours prior to that patient's body temperature increased to 38 to 38,5 °C. Intravenous Novalgin was administered and patient perspired profoundly. Patient was euthermic in three hours (36,5'C). In following 24 hours (till the death) patient's temperature was 36.5 to 37,3 °C without antipyretics.

Patient was immediately intubated and mechanical ventilation was initiated. Vasopressors were administered and infusion resuscitation with colloids and crystalloids was initiated. CT scan of the brain shows diffuse focal ischemia, predominantly left-sided. On a contrast image there is a picture of focal cerebritis or vasculitis (Fig. 3). On FCG curve appears block of right node of Tawara, there is elevation of myocardial isoenzymes (troponin I) proving myocardial ischemia. Also levels of C-radioactive protein multiplied. Chest and heart X-rays (in supine AP projection) is without pathological finding (Fig. 4). Patient died in 24 hours despite continual resuscitation.

Specimens taken from unhealed areas, oral cavity and urine 10 hours prior to death were analyzed and no microorganisms were found. Lumbar puncture was not performed, since no neurological infection was suspected.

Dissection was surprising-shocking:

1. Primary disease: Pemphigus Vulgaris,
2. Complication: Candidemia, Purulent leptomeningitis, abscess encephalitis (Fig. 5), abscesses in lungs (Fig. 6, 7), kidneys (Fig. 8, 9), spleen, and myocarditis (Fig. 10, 11).

Histological cutaneous and subcutaneous analyses did not show any candida!

Microbiology

Swabs from mouth, tonsils:

21^{st day: Escherichia Coli sporadic, yeast culture: negative}

22^{nd day: Escherichia Coli sporadic, yeast culture: negative}

42^{nd day: normal oral flora}

Urine, urinal catheter:

21^{st, 25st, 27st day: no microbes}

31^{st day: sporadic Staphylococcus epidermidis}

43^{st day: 104-5/ml Staphylococcus coagulase negat. (note: patient without catheter!)}

Chemically - urine is normal, urinary sediment: erythrocytes 0-4, leucocytes 0, cylindroids 0, and squamous epithelium 1-4)

47^{st day: no microbes}

Central venous catheter:

33^{st day: Enterococcus faecalis}

40^{st day: Enterococcus faecalis}

Hemoeulture:

36^th day: no microbes isolated from central or peripheral venous blood

Note: no other hemocultures taken, because there were no signs of laboratory or clinical sepsis or catheter fevers over 38,5 °C. Apart from the 46`h day of the first symptoms when fever 38-38,5 °C lasted only three hours and the on-call doctor did not indicate hemoculture samples to be taken.

Swabs from vagina:

30^th day: Staphylococcus coagulase negative, group Enterobacteriaceae Klebsiella

Swabs from the eroded areas (trunk, extremities):

21^th day: Escherichia coli, Staphylococcus aureus, yeast culture negative

25^th day: Pseudomonas species, yeast culture negative

28^th day: lOz Pseudomonas aeruginosa

10¹ Klebsiella sp, sporadically Enterobacter species, sporadically Staphylococcus aureus, sporadically Staphylococcus coagulase negative.

30^th day: no new microbes

32^nd day: no new microbes

34^th day: lOt Enterococcus faecalis (swabs only from back, otherwise no microbes)

36^th day: no new microbes

38^th day: no new microbes

40^th day: Enterococcus faecalis (only on the thorax)

42^th day: 102 Enterococcus faecalis (note: swabs from unhealed areas!!)

44^th day: no new microbes

46^th day: no new microbes

Chest and heart X-rays:

26^th day: morphological finding normal, central venous catheter in situ

31^th day: parenchyma without fresh focal changes, diaphragm smooth, heart shadow mildly broader to the left, hypertension in the respiratory circulation, central venous catheter in good position

46^th day: respiratory parenchyma without focal changes, diaphragm and angles free, heart shadow adequate in size, mildly sclerotic aorta, central venous catheter in situ (AP picture in bed)

CT scan of the brain:

47^th day from the first manifestation of the disease Pemphigus Vulgaris

Diffuse focal ischemia centers of the cerebellum and cerebrum predominantly left sided, post contrast picture nearly cerebritis or vasculitis.

Cardiology 47^th day:

Acute coronary lesion is not probable, more likely myocardial lesion as activation of systemic process (absence of typical ECG changes)

Electrocardiogram:

25^th day: sinus tachycardia, without pathology

47^th day (1:15 am): no signs of acute coronary lesion, blockage of the right Tawara node cannot be excluded

(8:50 am) - complete blockage of the right Tawara node.

Neurological examination:

47^th day (1:10 am): altered mental status on the level of sopor-coma, right sided hemiparesis, etiology unclear, differential diagnosis can not exclude vascular etiology.

(10:45 am): altered consciousness GCS 4-5??, vascular disease of the brain, secondary, focal ischemias of the cerebellum and cerebrum, right sided hemiparesis,(suppressed).

Ophthalmologic evaluation 4^th day:

Fundus of the eye: papilla of the right eye unclearly demarcated, prominence to +2D, haemorrhagia in the neighbourhood (congestive papilla OD???).

Laboratory tests have not been done before day 21" of the first supposed manifestation of the disease. It was because patient didn't seek any medical assistance for 20 days from the first generalized eruption for the vesicles (Pemphigus Vulgaris).

In conclusion we would like to point out, that in immunosupressed patients with long term therapy with corticoids, apart from prophylaxis by antimycotics, it is imperative to cultivate all microbiological material for mycoses (although clinically there are no signs of colonization with these agents).

REFERENCES

1. Tierney. LM., Jr., McPhee, SJ., Papadakis, MA., Schroeder, SA. Diagruiza a 106ba. 1" ed. Praha: Alberta, 1995, p. 91-93.
2. Sevcik, P., Cerny. V., Vftovec, J. et al. Intenziuni medicine. 1°' ed., Praha: Galen, 2000.
3. Schettlex, G.. Usadel. KH., Depperuan, D., Fridmann, B. et al. Repetitonunr. prakticheho Lehare.l" ed. Praha: Galen, 1995, p. 52, 706.

Address for correspondence:

Y. Kaloudova
Department of Burns anal Reconstructive Surgery
Faculty Hospital Rrno
Jihlauskk 20
625 00 Brno
Czech Republic