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Case #1 Display Date Oct. 21, 1997
INTRODUCTION
Phaeohyphomycosis includes a group of mycotic infections caused by dematiaceous fungi. In tissue these form either yeast like cells that are solitary or in short chains, or hyphae that are septate, often irregularly swollen, branched or unbranched, or any combination of these forms. These organisms cause a variety of uncommon to rare infections. The organisms grow in mycelial colonies and produce melanin-like pigments that give the colonies the characteristic dark color. Hematoxylin-and-eosin stains are preferred over the more commonly used Gomori's methenamine-silver stains in identifying and differentiating these organisms. [ref: 1, 3] 71 species that belong to 39 genera have been recognized human pathogens. [ref: 2, 3]
The individual genera and species are usually identified by morphologic criteria. Identification of species is difficult with isolates that do not fruit. Despite the morphologic differences among species, the illnesses they produce have many common features. Infection may result from either inoculation or inhalation (presumed) of the organism. The illness may be influenced by the immunocompetence of the host, the site of disease, and the extent of involvement. [ref: 1]
Phaeohyphomycosis was classified according to the organ or the level of skin involved into superficial type confined to stratum corneum, cutaneous type when keratinized tissues are involved, subcutaneous type including abscesses in the dermis or subcutis and systemic type that begins in lung and spreads to other organs.
Treatment of phaeohyphomycosis has been frustrating. Approaches include surgery and chemotherapy. Although resection of a single lesion may offer the best hope of cure, resection is not always possible. Treatment with amphotericin B has been frustrated by high rates of failure and frequent relapses among those who initially respond. The experience with ketoconazole and miconazole appears comparable in therapeutic disappointments. The role of in vitro susceptibility testing is unclear. The potential advantages of azole therapy in toxicity and ease of administration over amphotericin B warrant their active investigation. The rarity of the disease renders comparative trials impossible. The few initial reports on the use of itraconazole for treatment of phaeohyphomycosis, have been encouraging. [ref: 1] To our knowledge no reports on the use of fluconzole or saturated solution of potassium iodide (SSKI) in treatment of phaeohyphomycosis.
We report the first case of phaeohyphomycosis in Egypt and review our experience with fluconzole, SSKI and itraconazole treatment of phaeohyphomycosis.
CASE REPORT
A-17-year old male farmer, presented with generalized scaling since childhood. Palmo-planter hyperkeratosis was evident. Histopathology revealed hyperkeratosis, acanthosis, and elongation of the rete ridges.
The patient was diagnosed as congenital non-bullous ichthyosiform erythroderma.
Two years later multiple cystic nodules appeared over almost all of the body, including the scalp, face, extremities and abdomen. These new lesions were painless, firmly attached to the skin and freely movable over the underlying structures. Lesions were deep slowly growing in size and occasionally ulcerating and discharging thick greenish yellow discharge. Nodules of the face and scalp coalesced by time forming disfiguring hyperkeratotic plaques. The patient was otherwise clinically normal with no organomegaly, lympadenopathy or any other conspicuous changes.
Differential diagnosis:
- Cryptococcosis
- Chromoblastomycosis
- Actinomycosis
- Hodgkin's Iymphoma.
Investigations:
· Urine, stool, serum electrolytes, blood sugar, renal and liver functions were all normal.
· CBC revealed mild hypochromic microcytic anemia, normal leucocytic count and thrombocytosis.
· Serum Ig A was normal; Ig G, IgM, C3, C4 were all elevated (Table 1)
.Total lymphocytic count was normal (1887 / cmm), lymphocyte subsets were within normal absolute values(Table 2).
Table 1, Serum Immunoglobulins & Complement Concentrations
| Serum | Concentration | Ref. Range |
| Ig A | 227 mg /dl | 184-253 |
| Ig G | 2220 mg /dl | 1000 - 1388 |
| Ig M 1 | 50 mg /dl | 88 - 119 |
| C3 | 203 mg /dl | 115 - 150 |
| C4 | 36.9 mg /dl | 27.7 - 35.7 |
Table 2, Serum Lymphocyte Subsets & CD4 : CD8 Ratio:
| Subset | % | Absolute |
| CD3 | 78 (56 -78) | 1471(876-1900) |
| CD4 | 55 (32 - 60) | 1037 (450-1400) |
| CD8 | 22 (13 - 38) | 415 (190 - 725) |
| Ratio | Normal Range | |
| CD4:CD8 | 2.5 | 1 - 2.5 |
· Nitroblue Tetrazolium Test (NBT) was below normal range: 1.8% of Neutrophils reduced the dye (Normal = 2 - 8 %)
· ELISA test was negative for HIV and positive for Hepatitis-B.
· Bone scanning was normal with no abnormalities of the lung or CNS.
· Abdominal sonography showed periportal fibrosis of the liver.
· ECG and Echocardiography were normal.
· Non contrast CT Scan of the brain revealed :
1 . Huge extracalvarial subcutaneous collection in the right frontal region, The collection is multi-locular and has different attenuation values i.e. different fluid components
2. Normal attenuation value of the gray and white matter of both cerebral hemispheres.
3. No intracranial focal lesions, mass effect or mid-line shift.
4. Normal size and configuration of the supra and infra tentorial ventricular system.
5. Normal posterior fossa structures ands skull base.
· Aerobic and , anaerobic bacterial culturing was negative.
· Direct microscopic examination of the aspirate from the nodules revealed nothing even when stained by Gram or ZN.
· KOH smear of the aspirate revealed septate hyphae and conidiophores with distinct constrictions a characteristic feature of Phialophora species (Schwartz and Emmons, 1968)
-Fungal culturing : revealed darkly pigmented colonies which appeared macroscopically and microscopically characteristic of Phialophora richardsiae. [ref: 4]
Histopathology :
H&E stained sections revealed epidermal hyperplasia & inflammatory dermal reaction composed of histiocytes, Iymphoid cells and eosinophils. Many intradermal abscesses composed of neutrophils can be seen. PAS stained sections demonstrated darkly pigmented clusters of fungal elements.
Diagnosis:
Phaeohyphomycosis, subcutaneous type due to Phialophora richardsiae, (a member of a group of dematiaceous fungi). [ref: 4]
Treatment & Follow-up
· Fluconazole (Diflucan ®, Pfizer) 300 mg/day for 6 weeks resulted in no apparent change in the clinical picture that justified the first dose increase of fluconazole(450 mg /day). After 14 weeks there was reduction in the size of nodules and plaques but was considered slow.
· SSKI oral solution 5 drops increased 3 drops/day tds reaching and maintained on 50 drops tds was added to fluconazole. Minimal improvement after more than 35 weeks, led to further increasing the dose of fluconazole.
· Fluconazole was increased to 600 mg /day with the same dose of SSKI.
· After more than 33 weeks on the last dose, due to slow improvement, both fluconazole and SSKI were discontinued and Itraconazole (Sporanox®, Janssen - Cilag) 400 mg /day was started.
· After more than 17 weeks on itraconazole alone, marked reduction in the size and number of skin lesions were noted. · The ichthyosiform scales and palmo-plantar hyperkeratosis disappeared. · To accomplish a maximum response itraconazole was increased to 500 mg /day and still on the same dose for more than 6 weeks.
· The same dose will continue due to the satisfactory and relatively faster response.
· All treatment regimens were free of any side effects both clinically and biochemical. · The patient’s general and physical condition are improved markedly
Discussion
The clinical histologic and mycological findings in our case fits with the subcutaneous type of phaeohyphomycosis in an immunologically competent male with defective neutrophils, judged by NBT. The patient is a farmer in El-Menia province and possibly attracted infection from the farm environment. Treatment with fluconazole had therapeutic effect but was very slow. Oral SSKI apparently had no therapeutic value. Itraconzole was effective and relatively achieved rapid therapeutic response. Fluconazole in a dose ranged from 300-600 mg /day was tolerated by the patient and was free of biological side effects for over 65 weeks. The same finding applies to both SSKI that was tolerated for 47 weeks. Itraconazole proved to be safe in a dose ranged from 400-500 mg/day for 23 weeks. Although and additive effect may apply to the results obtained by our treatments, itraconazole in our judgment is the treatment of first choice in similar cases of phaeohyphomycosis.
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References
1 . Sharkey PK, Graybill JR, Rinaldi MG, Stevens DA,Tucker RM, Peterie JD, Hoeprich PD, Greer DL, Frenkel L, Counts GW, Goodrich J, Zellner S, Bradsher RW, van der Horst CM, Israel K, Pankey GA and Barranco CP. Itraconazole treatment of phaeohyphomycosis J AM ACAD DERMATOL 1990;23:577-86
2 . McGinnis MR. Chromoblastomycosis and phaeohyphomycosis: new concepts, diagnosis and mycology. J AM ACAD DERMATOL 1983;8:1-16
3 . Hsu MM and Lee JY, Cutaneous and subcutaneous phaeohyphomycosis caused by Exserohilum rostratum J AM ACAD DERMATOL 1993;28:340-4.
4 . Ikai-K; Tomono-H; Watanabe-S. Phaeohyphomycosis caused by Phialophora richardsiae. J-Am-Acad-Dermatol. 1988 Sep;19(3): 478-81
